Module 2 — Endocrine System PDF

Module 2 --- Endocrine System **ENDOCRINE SYSTEM VS NERVOUS SYSTEM** **TLO 2.1 --- BRIEFLY COMPARE THE ROLES OF THE NERVOUS AND ENDOCRINE SYSTEMS IN MAINTAINING HOMEOSTASIS.** **NERVOUS SYSTEM** **ENDOCRINE SYSTEM** ---------------------...

Module 2 --- Endocrine System **ENDOCRINE SYSTEM VS NERVOUS SYSTEM** **TLO 2.1 --- BRIEFLY COMPARE THE ROLES OF THE NERVOUS AND ENDOCRINE SYSTEMS IN MAINTAINING HOMEOSTASIS.** **NERVOUS SYSTEM** **ENDOCRINE SYSTEM** ------------------------- ------------------------------------------------ ------------------------------------------------------------------------------------- **Messenger** Nerve impulse Hormone **Transportation** Nerve axons Blood **Cells affected** Mainly muscles, glands, and other neurons All types of cells **Action** Muscular contractions and glandular secretions All types of changes in metabolic activities, growth, development, and reproduction **Time to act** Very quick (milliseconds) Slower (from seconds to days) **Duration of effects** Brief Longer The nervous and endocrine systems both play critical roles in maintaining homeostasis, but they differ in mechanisms, speed, and duration of action: **NERVOUS SYSTEM:** Uses electrical signals (action potentials) and chemical messengers (neurotransmitters). Acts rapidly, with effects occurring in milliseconds to seconds. Coordinates immediate responses to stimuli, such as reflexes or adjustments in heart rate and breathing. Targets specific cells or tissues via neural pathways. **ENDOCRINE SYSTEM:** Relies on chemical signals (hormones) transported through the bloodstream. Acts more slowly, with effects taking seconds to days to manifest. Regulates long-term processes like growth, metabolism, and reproduction. Affects broader target areas, as hormones can influence multiple organs simultaneously. Together, these systems integrate fast, localized responses (nervous system) with slower, systemic regulation (endocrine system) to maintain internal stability. **[COORDINATION OF HOMEOSTASIS -- NERVOUS VS. ENDOCRINE SYSTEMS ]** **HOMEOSTASIS COORDINATION** Cellular activities must be coordinated body wide. **Nervous System:** Innervates only a fraction of body cells. Commands are **specific** and **short-lived** (seconds). Many life processes (e.g., growth, development, reproduction) require **long-term control** (hours to years). **ROLE OF THE ENDOCRINE SYSTEM** Provides long-term control and complements the nervous system. Works together with the nervous system for **integrated control** of body systems across the lifespan. **SIMILARITIES** Both systems focus on **communication and control**. Use **chemical messengers** that bind to receptors on target tissues. **DIFFERENCES** **Endocrine System:** Uses hormones. Hormones travel via the **bloodstream** to distant tissues. Acts over long distances and durations. **Nervous System:** Uses **nerve impulses (action potentials)** along axons. Triggers release of **neurotransmitters** for local effects. Effects are immediate but short-term. **REVIEW** +-----------------------+-----------------------+-----------------------+ | **NERVOUS SYSTEM** | **BOTH** | **ENDOCRINE SYSTEM** | +=======================+=======================+=======================+ | Sends messages | Act on effector | Responses are slow, | | directly to effector | (target) organs to | but longer in | | (target) organs via | bring about change | duration | | nerves | | | | | Messages are in the | Chemical messengers | | Responses are quick | form of chemical | are hormones | | but short-lasting | messengers | | | | | Sends messages | | Messages are in the | Responses aim to | indirectly to | | form of electrical | maintain homeostasis | effector (target) | | impulses | | organs via blood | | | Chemical messenger | | | Chemical messengers | must bind to a | | | used are | receptor on the | | | neurotransmitters | target cell | | | | | | | | Uses | | | | adrenaline/noradrenal | | | | ine | | | | as a chemical | | | | messenger | | | | | | | | Usually regulated via | | | | negative feedback | | | | mechanisms | | +-----------------------+-----------------------+-----------------------+ Sends messages directly to effector (target) organs via nerves: Nervous System Responses are quick but short-lasting: Nervous System Messages are in the form of electrical impulses: Nervous System Act on effector (target) organs to bring about change: Both Responses are slow, but longer in duration: Endocrine System Messages are in the form of chemical messengers: Both Chemical messengers are hormones: Endocrine System Chemical messengers used are neurotransmitters: Nervous System Sends messages indirectly to effector (target) organs via blood: Endocrine System Responses aim to maintain homeostasis: Both Chemical messenger must bind to a receptor on the target cell: Both Uses adrenaline/noradrenaline as a chemical messenger: Both Usually regulated via negative feedback mechanisms: Both TLO 2.1 --- Briefly compare the roles of the nervous and endocrine systems in maintaining homeostasis. TLO 2.2 --- Briefly summarise the main classes of hormones and their mechanism of action. TLO 2.2.1 --- Peptide, amine, and steroid hormones. TLO 2.2.2 --- Cell surface and intracellular receptors. TLO 2.3 --- Explain the relationship between the hypothalamus and pituitary gland in the regulation of endocrine function including. TLO 2.3.1 --- Functions and control of release of the posterior pituitary hormones. TLO 2.3.2 --- Functions and control of hormones secreted by the anterior pituitary. TLO 2.4 --- Describe the main functions and secretion of hormones from the adrenal gland. TLO 2.5 --- Describe the main functions and secretion of hormones from the pancreas involved in BGL homeostasis. TLO 2.6 --- Explain the roles of parathyroid hormone (PTH), calcitonin and vitamin D in calcium homeostasis. TLO 2.7 --- Explain how endocrine system function alters across the lifespan. **CLASSES OF HORMONES** **TLO 2.2 --- BRIEFLY SUMMARISE THE MAIN CLASSES OF HORMONES AND THEIR MECHANISM OF ACTION.** **WHAT IS A HORMONE?** Hormones are bloodborne chemical messengers produced by endocrine cells. These hormones are secreted directly into the bloodstream and exist in low concentrations. Hormones have a nonspecific distribution, meaning they travel throughout the body via the bloodstream. **HOW DO HORMONES HAVE EFFECTS?** Hormones affect specific target cells, not every cell. Target cells have specialized receptors that bind specific hormones. **Example:** Insulin binds to insulin receptors, adrenaline binds to adrenaline receptors. Hormones can affect cells only if their specific receptor is present on that cell. **RECEPTORS** Receptors are specialized proteins that bind to hormones. Cells may have multiple types of receptors, allowing them to respond to a variety of hormones. Receptors can be located: On the cell membrane: For water-soluble hormones. Inside the cell (cytoplasm or nucleus): For fat-soluble hormones. **TYPES OF HORMONES** **WATER-SOLUBLE HORMONES** Cannot cross the plasma membrane easily. Bind to receptors on or in the cell membrane. Effects are indirect, triggering a second messenger system (a series of molecular events within the cell). Examples: Insulin, parathyroid hormone, adrenaline. **FAT-SOLUBLE HORMONES** Can cross the plasma membrane easily. Bind to receptors in the cytoplasm or nucleus. Effects are direct, interacting with DNA to alter gene expression. Examples: Cortisol, aldosterone, sex hormones, vitamin D, thyroid hormone. **MECHANISMS OF ACTION** Hormones can alter target cell activity by changing: Enzyme activity (e.g., metabolic reactions). Transport of substances across the cell membrane. Gene expression, affecting protein production. **ENZYMATIC REACTIONS** Enzymes control the rate of biochemical reactions (e.g., metabolism). Hormones like thyroid hormone affect enzyme activity, thus regulating metabolic rate. **TRANSPORT OF SUBSTANCES** Hormones can influence the movement of substances across cell membranes. Insulin triggers the opening of glucose channels in the membrane, allowing glucose to enter the cell. **GENE EXPRESSION** Hormones can turn genes on or off, affecting protein production in cells. Example: Cortisol may increase or decrease the production of specific proteins by interacting with DNA. Classification of hormones based upon chemical class Hormones can be further classified based upon their chemical class (i.e. their structural make-up). Peptide hormones \[and protein hormones\] are chains of amino acids joined together. They are water soluble. Smaller chains (3-49 amino acids in length) are known as peptide hormones (e.g. anti-diuretic hormone and oxytocin). Longer chains (50-200 amino acids in length) are known as protein hormones (e.g. growth hormone and insulin). Most hormones in your body are peptide or protein hormones. Amine hormones are synthesised from a single amino acid (quite often tyrosine). They are water soluble. For example, adrenaline, nor-adrenaline, and dopamine (the catecholamines) are synthesised by modifying tyrosine. Serotonin and melatonin are derived from tryptophan. Steroid hormones are derived from cholesterol. They are fat/lipid soluble. Examples include aldosterone, cortisol, calcitriol, testosterone, oestrogens, and progesterone. Responsiveness to hormones The responsiveness of a target cell to a hormone depends on: Concentration of hormone in the blood: Increasing hormone concentration will generally correlate to a greater response (assuming the hormone can bind to its receptor). The abundance of hormone receptors on the target cell: Up-regulation of hormone receptors (i.e., there are more present on/in the target cell) will result in a more vigorous response. Conversely, down-regulation of receptors will decrease response to a hormone by a target cell. Influences exerted by other hormones: Sometimes, a hormone\'s effect upon a target cell is dependent upon a recent or simultaneous exposure to a second hormone. For example, adrenaline alone weakly stimulates lipolysis, but when small amounts of thyroid hormones are present, the same amount of adrenaline simulates lipolysis much more strongly. Interaction of hormones Hormones can affect each other\'s actions. When two hormones enhance each other\'s actions, this is termed a synergistic effect. e.g., glucagon and adrenaline both act to raise blood glucose. When two hormones oppose each other\'s actions, this is termed an antagonistic effect. e.g., insulin acts to decrease blood glucose levels and glucagon acts to raise blood glucose levels. **TLO 2.2.1 --- PEPTIDE, AMINE, AND STEROID HORMONES.** +-----------------------+-----------------------+-----------------------+ | **PEPTIDE HORMONES** | | | +=======================+=======================+=======================+ | **Structure** | Composed of chains of | | | | amino acids, ranging | | | | from small peptides | | | | (e.g., oxytocin) to | | | | larger proteins | | | | (e.g., insulin). | | +-----------------------+-----------------------+-----------------------+ | **Solubility** | Water-soluble, so | | | | they cannot cross the | | | | lipid bilayer of the | | | | plasma membrane. | | +-----------------------+-----------------------+-----------------------+ | **Examples** | Insulin: Regulates | Parathyroid Hormone | | | glucose uptake. | (PTH): Maintains | | | | calcium homeostasis. | +-----------------------+-----------------------+-----------------------+ | **Mechanism of | Bind to cell surface | | | action** | receptors on the | | | | plasma membrane. | | | | | | | | Hormone binding | | | | triggers a signal | | | | transduction pathway, | | | | often involving | | | | secondary messengers | | | | such as cyclic AMP | | | | (cAMP) or calcium | | | | ions. | | | | | | | | This cascade | | | | amplifies the signal, | | | | resulting in | | | | physiological changes | | | | such as enzyme | | | | activation, channel | | | | opening, or other | | | | cellular responses. | | | | | | | | Indirect action: The | | | | hormone does not | | | | enter the cell but | | | | initiates | | | | intracellular changes | | | | via signalling | | | | pathways. | | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | **AMINE HORMONES** | | | +=======================+=======================+=======================+ | **Structure** | Derived from single | | | | amino acids, | | | | primarily tyrosine or | | | | tryptophan. | | +-----------------------+-----------------------+-----------------------+ | **Solubility** | Can be either | | | | water-soluble or | | | | lipid-soluble, | | | | depending on the | | | | specific hormone. | | +-----------------------+-----------------------+-----------------------+ | **Examples** | Adrenaline | Thyroid Hormones (T3 | | | (Epinephrine): A | and T4): | | | water-soluble hormone | Lipid-soluble | | | that mediates the | hormones that | | | fight-or-flight | regulate metabolism. | | | response. | | +-----------------------+-----------------------+-----------------------+ | **Mechanism of | Water-soluble amine | | | action** | hormones (e.g., | | | | adrenaline) bind to | | | | cell surface | | | | receptors and | | | | activate second | | | | messenger systems. | | | | | | | | Lipid-soluble amine | | | | hormones (e.g., | | | | thyroid hormones) | | | | cross the plasma | | | | membrane and bind to | | | | intracellular | | | | receptors. Once | | | | bound, the | | | | hormone-receptor | | | | complex interacts | | | | with DNA to modulate | | | | gene expression, | | | | leading to | | | | longer-term changes | | | | in cell function. | | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | **STEROID HORMONES** | | | +=======================+=======================+=======================+ | **Structure** | Derived from | | | | cholesterol, | | | | consisting of four | | | | interconnected carbon | | | | rings. | | +-----------------------+-----------------------+-----------------------+ | **Solubility** | Lipid-soluble, | | | | enabling them to | | | | diffuse through the | | | | cell membrane. | | +-----------------------+-----------------------+-----------------------+ | **Examples** | Cortisol: A stress | Testosterone and | | | hormone that | Estrogen: Regulate | | | regulates glucose | reproductive | | | metabolism and immune | functions and | | | responses. | secondary sexual | | | | characteristics. | +-----------------------+-----------------------+-----------------------+ | **Mechanism of | Cross the plasma | | | action** | membrane and bind to | | | | intracellular | | | | receptors located in | | | | the cytoplasm or | | | | nucleus. | | | | | | | | The hormone-receptor | | | | complex binds to | | | | specific DNA | | | | sequences (hormone | | | | response elements) to | | | | regulate the | | | | transcription of | | | | target genes. | | | | | | | | Direct action: Leads | | | | to the synthesis of | | | | specific proteins, | | | | altering cellular | | | | function. This | | | | process takes longer | | | | but has prolonged | | | | effects. | | +-----------------------+-----------------------+-----------------------+ **TLO 2.2.2 --- CELL SURFACE AND INTRACELLULAR RECEPTORS.** **CELL SURFACE RECEPTORS** **Location:** Embedded in the plasma membrane. **Hormone Types:** Water-soluble hormones, including peptide hormones and some amine hormones (e.g., adrenaline). **Function:** Recognize and bind to specific hormones. Trigger signal transduction pathways, which involve secondary messengers like cAMP, inositol triphosphate (IP3), or calcium ions. Amplify the hormone\'s signal, leading to changes in enzyme activity, ion channel function, or other cellular processes. **Examples of Hormones Using Cell Surface Receptors:** **Insulin:** Activates glucose transporters to regulate blood sugar. **Adrenaline:** Activates the cAMP pathway to increase heart rate and energy availability. **INTRACELLULAR RECEPTORS** **Location:** Found in the cytoplasm or nucleus of the cell. **Hormone Types:** Lipid-soluble hormones, including steroid and thyroid hormones. **Function:** Hormones diffuse across the plasma membrane and bind to intracellular receptors. The hormone-receptor complex interacts directly with DNA at specific regulatory regions (hormone response elements). Modulates gene expression by turning specific genes on or off, leading to the synthesis or suppression of proteins. **Examples of Hormones Using Intracellular Receptors:** **Cortisol:** Regulates stress responses by influencing glucose metabolism and inflammation. **Thyroid Hormones (T3 and T4):** Increase metabolic rate by upregulating genes involved in energy production. **KEY DIFFERENCES BETWEEN MECHANISMS OF HORMONE ACTION** ---------------------------------------------------------- ----------------------------------------------------------- ------------------------------------------- **PROPERTY** **CELL SURFACE RECEPTORS** **INTRACELLULAR RECEPTORS** **Hormone Type** Water-soluble (peptide, some amine hormones) Lipid-soluble (steroid, thyroid hormones) **Location of Receptor** On the plasma membrane In the cytoplasm or nucleus **Mode of action** Indirect via signal transduction and secondary messengers Direct regulation of gene expression **Speed of action** Rapid but short-lived Slower onset, longer-lasting effects **REVIEW** **WATER SOLUBLE** **FAT/LIPID SOLUBLE** ------------------------------------------ ------------------------------------------------------------------------------------- ----------------------------------------------------------------------------------------- **Description** Hydrophilic Hydrophobic **Chemical class** Peptide, amine Steroid **Examples** Insulin, glucagon, growth hormone, insulin-like growth factor 1 Testosterone, oestrogen, cortisol, androgens **Hormone transport in the blood** Most circulate 'free' in the watery blood plasma (not attached to another molecule) Most require transport/carrier (or 'binding proteins') to travel in watery blood plasma **Half-life** Relatively short because not bound to binding proteins Extended because bound to binding proteins **Location of receptors** Cell membrane Cytoplasm or nucleus **Mechanism of action** Indirect (requires 2^nd^ messenger system) Direct (hormone receptor complex alters gene) **Speed of response to hormone binding** Rapid because secondary messengers modify existing proteins Relatively slow because requires activation of genes **HYPOTHALAMUS & PITUITARY GLAND** **TLO 2.3 --- EXPLAIN THE RELATIONSHIP BETWEEN THE HYPOTHALAMUS AND PITUITARY GLAND IN THE REGULATION OF ENDOCRINE FUNCTION INCLUDING.** +-----------------------------------------------------------------------+ | **Did you know?** | | | | The pituitary gland is the size and shape of a large pea, yet it is | | the "master gland" of the body. Despite its small size, its hormones | | control most of the other glands of the body. The pituitary gland | | does, however, have its own master---the hypothalamus. | +-----------------------------------------------------------------------+ **Endocrine Glands and Their Hormones** The endocrine system coordinates growth, development, reproduction, metabolism, and homeostasis. **Hypothalamus** The hypothalamus is not always considered an endocrine gland as it is part of the nervous system. However, it is included in this chapter because of its vital connection to the pituitary gland. The hypothalamus: Releases a number of hormones that control the secretions of the pituitary gland Synthesizes two hormones that are then transported to, and stored in, the posterior pituitary gland. These hormones are oxytocin and antidiuretic hormone (vasopressin). **Pituitary gland** The pituitary gland is located in the hypophyseal fossa of the sphenoid bone and is found behind the nose and between the eyes. It is attached to the hypothalamus by a stalk and comprises an anterior and a posterior portion. +-----------------------------------------------------------------------+ | **Study tip** | | | | The charts on the following pages discuss the endocrine glands, their | | hormones, and their functions. They also list examples of what can go | | wrong if the gland is not functioning properly. Most of these | | disorders are due to either overproduction (hypersecretion) or | | underproduction (hyposecretion) of hormones. Some of these disorders | | are discussed in more detail at the end of this chapter. However, | | they have been included here to help you understand the functions of | | the glands. | +-----------------------------------------------------------------------+ **Figure: Endocrine glands of the male and female** **Hypothalamus and pituitary gland, and their blood supply.** Releasing and inhibiting hormones synthesised by hypothalamic neurosecretory cells are transported within axons and released at the axon terminals. The hormones diffuse into capillaries of the primary plexus of the hypophyseal portal system and are carried by the hypophyseal portal veins to the secondary plexus of the hypophyseal portal system for distribution to target cells in the anterior pituitary. Hypothalamic hormones are an important link between the nervous and endocrine systems. The pituitary gland, also called the hypophysis, is a pea-sized gland located in a depression of the sphenoid bone. It is attached to the undersurface of the hypothalamus by a short stalk called the infundibulum. The pituitary gland contains two main parts: The anterior pituitary gland The posterior pituitary gland. The major hormones and their target glands are shown in Fig. 14.4. **Figure: The Pituitary Gland and its Relationship to the Hypothalamus.** The hypothalamus communicates with the anterior pituitary via a capillary system (blue) and with the posterior pituitary via nerve tracts (yellow). Anterior and posterior pituitary hormones are shown with their target tissues (**bold**). **TLO 2.3.1 --- FUNCTIONS AND CONTROL OF RELEASE OF THE POSTERIOR PITUITARY HORMONES.** The posterior pituitary gland is also controlled by the hypothalamus, but not through the secretion of releasing hormones. The posterior pituitary gland is an extension of the hypothalamus. It is composed of nervous tissue and is sometimes called the neurohypophysis. The two hormones of the posterior pituitary gland are produced in the hypothalamus and transported to the gland, where they are stored until needed. The two hormones are antidiuretic hormone (ADH) and oxytocin. **ANTIDIURETIC HORMONE** Antidiuretic hormone (ADH) is released from the posterior pituitary gland in an attempt to conserve water. The primary target organ for ADH is the kidney. ADH causes the kidney to reabsorb water from the urine and return it to the blood. In so doing, the amount of urine that the kidney excretes decreases---hence, the term antidiuretic hormone (anti- means 'against'; diuresis means 'urine flow'). ADH is released in response to a concentrated blood (increased osmolarity) and decreased blood volume; both occur in dehydration. The hypothalamic cells that sense the increasing osmolarity of the blood are called osmoreceptors. Other triggers for the release of ADH are stress, trauma, and drugs such as morphine. Alcohol, in contrast, inhibits ADH secretion---hence the excessive urination that accompanies beer drinking. In the absence of ADH, a profound diuresis occurs, and the person may excrete up to 25 L/day of dilute urine. This ADH deficiency disease is called diabetes insipidus and should not be confused with the more common diabetes mellitus, which is an insulin deficiency. ADH also causes the blood vessels to constrict, thereby elevating blood pressure. Due to this blood pressure-elevating effect, ADH is also called vasopressin (a vasopressor agent is one that elevates blood pressure). **OXYTOCIN** The second posterior pituitary hormone is oxytocin. The target organs of oxytocin (ox-see-TOH-sin) in the female are the uterus and the mammary glands (breasts). Oxytocin release occurs in response to neuroendocrine reflexes, that is, in response to signals from the nervous system. Oxytocin stimulates the muscles of the uterus to contract and plays a role in labour and the delivery of a baby. The word oxytocin literally means 'swift birth' and an oxytocic drug is one that causes uterine contractions and hastens delivery. Intravenous oxytocin is often administered to initiate labour. Oxytocin also plays a role in breastfeeding. When the baby suckles at the breast, oxytocin is released and stimulates contraction of the smooth muscles around the mammary ducts within the breasts, thereby releasing breast milk. The release of milk in response to suckling is called the milk let-down reflex (see Chapter 24 for a description). The role of oxytocin in the male is not fully understood; it is thought to help move the semen along the male reproductive tract. Oxytocin has recently been dubbed the bonding or relationship hormone; it seems that a high blood level of oxytocin generates feelings of goodwill and an urge to be cooperative, protective, and friendly. It makes sense that breastfeeding and the release of oxytocin facilitate bonding between mother and infant. +-----------------+-----------------+-----------------+-----------------+ | **Hormone** | **Target | **Actions** | **Disorders and | | | tissue** | | diseases** | +=================+=================+=================+=================+ | ***POSTERIOR | | | | | PITUITARY | | | | | GLAND*** | | | | | | | | | | The posterior | | | | | pituitary gland | | | | | does not | | | | | synthesise | | | | | hormones. | | | | | Instead, it | | | | | stores and | | | | | releases | | | | | hormones | | | | | synthesised by | | | | | the | | | | | hypothalamus. | | | | +-----------------+-----------------+-----------------+-----------------+ | **Oxytocin | Uterus, mammary | Stimulates | No known | | (OT)** | glands | contraction of | disorders | | | | uterus during | | | | | labour and | | | | | stimulates the | | | | | "milk let-down" | | | | | reflex during | | | | | lactation | | +-----------------+-----------------+-----------------+-----------------+ | **Antidiuretic | Kidneys, | Antidiuretic | Hyposecretion: | | hormone (ADH) | sudoriferous | effect (i.e. | Diabetes | | or | glands, blood | conserves water | insipidus | | vasopressin** | vessels | by decreasing | | | | | urine volume | | | | | and | | | | | perspiration), | | | | | raises blood | | | | | pressure | | +-----------------+-----------------+-----------------+-----------------+ **TLO 2.3.2 --- FUNCTIONS AND CONTROL OF HORMONES SECRETED BY THE ANTERIOR PITUITARY.** Anterior pituitary The anterior pituitary or adenohypophysis secretes hormones that regulate a wide range of bodily activities, from growth to reproduction. Release of anterior pituitary hormones is stimulated by releasing hormones and suppressed by inhibiting hormones from the hypothalamus. Thus, the hypothalamic hormones are an important link between the nervous and endocrine systems. Hypophyseal portal system Hypothalamic hormones that release or inhibit anterior pituitary hormones reach the anterior pituitary through a portal system. Usually, blood passes from the heart through an artery to a capillary to a vein and back to the heart. In a portal system, blood flows from one capillary network into a portal vein, and then into a second capillary network before returning to the heart. The name of the portal system indicates the location of the second capillary network. In the hypophyseal portal system (hī′-pō-FIZ-ē-al), blood flows from capillaries in the hypothalamus into portal veins that carry blood to capillaries of the anterior pituitary. The superior hypophyseal arteries, branches of the internal carotid arteries, bring blood into the hypothalamus (figure 18.5a). At the junction of the median eminence of the hypothalamus and the infundibulum, these arteries divide into a capillary network called the primary plexus of the hypophyseal portal system. From the primary plexus, blood drains into the hypophyseal portal veins that pass down the outside of the infundibulum. In the anterior pituitary, the hypophyseal portal veins divide again and form another capillary network called the secondary plexus of the hypophyseal portal system. Above the optic chiasm are clusters of specialised neurons called neurosecretory cells (figure 18.5b). They synthesise the hypothalamic releasing and inhibiting hormones in their cell bodies and package the hormones inside vesicles, which reach the axon terminals by axonal transport. Nerve impulses stimulate the vesicles to undergo exocytosis. The hormones then diffuse into the primary plexus of the hypophyseal portal system. Quickly, the hypothalamic hormones flow with the blood through the portal veins and into the secondary plexus. This direct route permits hypothalamic hormones to act immediately on anterior pituitary cells, before the hormones are diluted or destroyed in the general circulation. Hormones secreted by anterior pituitary cells pass into the secondary plexus capillaries, which drain into the anterior hypophyseal veins and out into the general circulation. Anterior pituitary hormones then travel to target tissues throughout the body. Those anterior pituitary hormones that act on other endocrine glands are called tropic hormones (TRŌ-pik) or tropins. Types of anterior pituitary cells and their hormones Five types of anterior pituitary cells --- somatotrophs, thyrotrophs, gonadotrophs, lactotrophs, and corticotrophs --- secrete seven hormones (table 18.3). 1 --- Somatotrophs secrete human growth hormone (hGH), also known as somatotropin (somato- = body; -tropin = change). Human growth hormone in turn stimulates several tissues to secrete insulin-like growth factors (IGFs), hormones that stimulate general body growth and regulate aspects of metabolism. 2 --- Thyrotrophs secrete thyroid-stimulating hormone (TSH), also known as thyrotropin (thyro- = pertaining to the thyroid gland). TSH controls the secretions and other activities of the thyroid gland. 3 --- Gonadotrophs (gonado- = seed) secrete two gonadotropins: follicle-stimulating hormone (FSH) and luteinising hormone (LH). FSH and LH both act on the gonads. They stimulate secretion of oestrogens and progesterone and the maturation of oocytes in the ovaries, and they stimulate sperm production and secretion of testosterone in the testes. 4 --- Lactotrophs (lacto- = milk) secrete prolactin (PRL), which initiates milk production in the mammary glands. 5 --- Corticotrophs secrete adrenocorticotropic hormone (ACTH), also known as corticotropin (cortico- = rind or bark), which stimulates the adrenal cortex to secrete glucocorticoids such as cortisol. Some corticotrophs, remnants of the pars intermedia, also secrete melanocyte-stimulating hormone (MSH). Control of secretion by the anterior pituitary Secretion of anterior pituitary hormones is regulated in two ways. First, neurosecretory cells in the hypothalamus secrete five releasing hormones, which stimulate secretion of anterior pituitary hormones, and two inhibiting hormones, which suppress secretion of anterior pituitary hormones (table 18.3). Second, negative feedback in the form of hormones released by target glands decreases secretions of three types of anterior pituitary cells (figure 18.6). In such negative feedback loops, the secretory activity of thyrotrophs, gonadotrophs, and corticotrophs decreases when blood levels of their target gland hormones rise. For example, adrenocorticotropic hormone (ACTH) stimulates the cortex of the adrenal gland to secrete glucocorticoids, mainly cortisol. In turn, an elevated blood level of cortisol decreases secretion of both corticotropin and corticotropin-releasing hormone (CRH) by suppressing the activity of the anterior pituitary corticotrophs and hypothalamic neurosecretory cells. Human growth hormone and insulinlike growth factors Somatotrophs are the most numerous cells in the anterior pituitary, and human growth hormone (hGH) is the most plentiful anterior pituitary hormone. The main function of hGH is to promote synthesis and secretion of small protein hormones called insulinlike growth factors or somatomedins (sō′-ma-tō- MĒ-dins). In response to human growth hormone, cells in the liver, skeletal muscles, cartilage, bones, and other tissues secrete IGFs, which may either enter the bloodstream from the liver or act locally in other tissues as autocrines or paracrines. The functions of IGFs include the following. 1. IGFs cause cells to grow and multiply by increasing uptake of amino acids into cells and accelerating protein synthesis. IGFs also decrease the breakdown of proteins and the use of amino acids for ATP production. Due to these effects of the IGFs, human growth hormone increases the growth rate of the skeleton and skeletal muscles during childhood and the teenage years. In adults, human growth hormone and IGFs help maintain the mass of muscles and bones and promote healing of injuries and tissue repair. 2. IGFs also enhance lipolysis in adipose tissue, which results in increased use of the released fatty acids for ATP production by body cells. 3. In addition to affecting protein and lipid metabolism, human growth hormone and IGFs influence carbohydrate metabolism by decreasing glucose uptake, which decreases the use of glucose for ATP production by most body cells. This action spares glucose so that it is available to neurons for ATP production in times of glucose scarcity. IGFs and human growth hormone may also stimulate liver cells to release glucose into the blood. Somatotrophs in the anterior pituitary release bursts of human growth hormone every few hours, especially during sleep. Their secretory activity is controlled mainly by two hypothalamic hormones: (1) growth hormone--releasing hormone (GHRH) promotes secretion of human growth hormone, and (2) growth hormone--inhibiting hormone (GHIH) suppresses it. A major regulator of GHRH and GHIH secretion is the blood glucose level (figure 18.7). ❶ Hypoglycaemia (hī′-pō-glī-SĒ-mē-a), an abnormally low blood glucose concentration, stimulates the hypothalamus to secrete GHRH, which flows towards the anterior pituitary in the hypophyseal portal veins. ❷ On reaching the anterior pituitary, GHRH stimulates somatotrophs to release human growth hormone. ❸ Human growth hormone stimulates secretion of insulinlike growth factors, which speed breakdown of liver glycogen into glucose, causing glucose to enter the blood more rapidly. ❹ As a result, blood glucose rises to the normal level (about 90 mg/100 mL of blood plasma). ❺ An increase in blood glucose above the normal level inhibits release of GHRH. ❻ Hyperglycaemia (hī′-per-glī-SĒ-mē-a), an abnormally high blood glucose concentration, stimulates the hypothalamus to secrete GHIH (while inhibiting the secretion of GHRH). ❼ On reaching the anterior pituitary in portal blood, GHIH inhibits secretion of human growth hormone by somatotrophs. ❽ A low level of human growth hormone and IGFs slows breakdown of glycogen in the liver, and glucose is released into the blood more slowly. ❾ Blood glucose falls to the normal level. ❿ A decrease in blood glucose below the normal level (hypoglycaemia) inhibits release of GHIH. Other stimuli that promote secretion of human growth hormone include decreased fatty acids and increased amino acids in the blood; deep sleep (stages 3 and 4 of non-rapid eye movement sleep); increased activity of the sympathetic division of the autonomic nervous system, such as might occur with stress or vigorous physical exercise; and other hormones, including glucagon, oestrogens, cortisol, and insulin. Factors that inhibit human growth hormone secretion are increased levels of fatty acids and decreased levels of amino acids in the blood; rapid eye movement sleep; emotional deprivation; obesity; low levels of thyroid hormones; and human growth hormone itself (through negative feedback). Growth hormone--inhibiting hormone (GHIH), alternatively known as somatostatin, also inhibits the secretion of human growth hormone. Thyroid-stimulating hormone Thyroid-stimulating hormone (TSH) stimulates the synthesis and secretion of the two thyroid hormones, triiodothyronine (T3) and thyroxine (T4), both produced by the thyroid gland. Thyrotropin-releasing hormone (TRH) from the hypothalamus controls TSH secretion. Release of TRH in turn depends on blood levels of T3 and T4; high levels of T3 and T4 inhibit secretion of TRH via negative feedback. There is no thyrotropin-inhibiting hormone. The release of TRH is explained later in the chapter (see figure 18.12). Follicle-stimulating hormone In females, the ovaries are the targets for follicle-stimulating hormone (FSH). Each month FSH initiates the development of several ovarian follicles, saclike arrangements of secretory cells that surround a developing oocyte. FSH also stimulates follicular cells to secrete oestrogens (female sex hormones). In males, FSH stimulates sperm production in the testes. Gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates FSH release. Release of GnRH and FSH is suppressed by oestrogens in females and by testosterone (the principal male sex hormone) in males through negative feedback systems. There is no gonadotropin-inhibiting hormone. Luteinising hormone In females, luteinising hormone (LH) triggers ovulation, the release of a secondary oocyte (future ovum) by an ovary. LH stimulates formation of the corpus luteum (structure formed after ovulation) in the ovary and the secretion of progesterone (another female sex hormone) by the corpus luteum. Together, FSH and LH also stimulate secretion of oestrogens by ovarian cells. Oestrogens and progesterone prepare the uterus for implantation of a fertilised ovum and help prepare the mammary glands for milk secretion. In males, LH stimulates cells in the testes to secrete testosterone. Secretion of LH, like that of FSH, is controlled by gonadotropin-releasing hormone (GnRH). Prolactin Prolactin (PRL), together with other hormones, initiates and maintains milk production by the mammary glands. By itself, prolactin has only a weak effect. Only after the mammary glands have been primed by oestrogens, progesterone, glucocorticoids, human growth hormone, thyroxine, and insulin, which exert permissive effects, does PRL bring about milk production. Ejection of milk from the mammary glands depends on the hormone oxytocin, which is released from the posterior pituitary. Together, milk production and ejection constitute lactation. The hypothalamus secretes both inhibitory and excitatory hormones that regulate prolactin secretion. In females, prolactin-inhibiting hormone (PIH), which is dopamine, inhibits the release of prolactin from the anterior pituitary most of the time. Each month, just before menstruation begins, the secretion of PIH diminishes and the blood level of prolactin rises, but not enough to stimulate milk production. Breast tenderness just before menstruation may be caused by elevated prolactin. As the menstrual cycle begins anew, PIH is again secreted and the prolactin level drops. During pregnancy, the prolactin level rises, stimulated by prolactin-releasing hormone (PRH) from the hypothalamus. The sucking action of a nursing infant causes a reduction in hypothalamic secretion of PIH. The function of prolactin is not known in males, but its hypersecretion causes erectile dysfunction (impotence, the inability to have an erection of the penis). In females, hypersecretion of prolactin causes galactorrhea (inappropriate lactation) and amenorrhea (absence of menstrual cycles). Adrenocorticotropic hormone Corticotrophs secrete mainly adrenocorticotropic hormone (ACTH). ACTH controls the production and secretion of cortisol and other glucocorticoids by the cortex (outer portion) of the adrenal glands. Corticotropin-releasing hormone (CRH) from the hypothalamus stimulates secretion of ACTH by corticotrophs. Stress-related stimuli, such as low blood glucose or physical trauma, and interleukin-1, a substance produced by macrophages, also stimulate release of ACTH. Glucocorticoids inhibit CRH and ACTH release via negative feedback. Melanocyte-stimulating hormone Melanocyte-stimulating hormone (MSH) increases skin pigmentation in amphibians by stimulating the dispersion of melanin granules in melanocytes. Its exact role in humans is unknown, but the presence of MSH receptors in the brain suggests it may influence brain activity. There is little circulating MSH in humans. However, continued administration of MSH for several days does produce a darkening of the skin. Excessive levels of corticotropin-releasing hormone (CRH) can stimulate MSH release; dopamine inhibits MSH release. +-----------------+-----------------+-----------------+-----------------+ | **Hormone** | **Target | **Actions** | **Disorders and | | | tissue** | | diseases** | +=================+=================+=================+=================+ | ***ANTERIOR | | | | | PITUITARY | | | | | GLAND*** | | | | | | | | | | All the | | | | | hormones | | | | | released by the | | | | | anterior | | | | | pituitary | | | | | gland, except | | | | | for human | | | | | growth hormone, | | | | | regulate other | | | | | endocrine | | | | | glands. | | | | +-----------------+-----------------+-----------------+-----------------+ | **Human growth | Bone, muscle, | Stimulates | Hyposecretion: | | hormone (hGH) | cartilage, and | growth and | Pituitary | | or | other tissue | regulates | dwarfism | | somatotropin** | | metabolism | | | | | | Hypersecretion: | | | | | Gigantism, | | | | | acromegaly | +-----------------+-----------------+-----------------+-----------------+ | **Thyroid-stimu | Thyroid gland | Controls the | Hyposecretion: | | lating | | thyroid gland | Myxedema | | hormone (TSH) | | | | | or | | | Hypersecretion: | | thyrotropin** | | | Graves' disease | +-----------------+-----------------+-----------------+-----------------+ | **Follicle-stim | Ovaries and | In females: | Hyposecretion: | | ulating | testes | stimulates the | Sterility | | hormone (FSH)** | | development of | | | | | oocytes (egg | | | | | cells or | | | | | immature ova) | | | | | | | | | | In males: | | | | | stimulates the | | | | | production of | | | | | sperm | | +-----------------+-----------------+-----------------+-----------------+ | **Luteinising | Ovaries and | In females: | Hyposecretion: | | hormone (LH)** | testes | stimulates | Sterility | | | | ovulation, the | | | | | formation of | Hypersecretion: | | | | the corpus | Stein-Leventhal | | | | luteum, and | syndrome | | | | secretion of | (Polycystic | | | | oestrogens and | ovary syndrome, | | | | progesterone | PCOS) | | | | | | | | | In males: | | | | | stimulates the | | | | | production of | | | | | testosterone | | +-----------------+-----------------+-----------------+-----------------+ | **Prolactin | Mammary glands | In females: | Hypersecretion | | (PRL) or | | stimulates the | in females: | | lactogenic | | secretion of | Galactorrhea | | hormone** | | milk from the | (abnormal | | | | breasts | lactation), | | | | | amenorrhea | | | | In males: | (absence of | | | | action is | menstrual | | | | unknown | cycles) | +-----------------+-----------------+-----------------+-----------------+ | **Adrenocortico | Adrenal cortex | Stimulates and | Hyposecretion: | | tropic | | controls the | Addison's | | hormone (ACTH) | | adrenal cortex | disease | | or | | | | | corticotropin** | | | Hypersecretion: | | | | | Cushing's | | | | | syndrome | +-----------------+-----------------+-----------------+-----------------+ | **Melanocyte-st | Skin | Exact actions | No known | | imulating | | are unknown, | disorders | | hormone (MSH)** | | but can cause | | | | | darkening of | | | | | the skin | | +-----------------+-----------------+-----------------+-----------------+ **ADRENAL GLAND** **TLO 2.4 --- DESCRIBE THE MAIN FUNCTIONS AND SECRETION OF HORMONES FROM THE ADRENAL GLAND.** The adrenal glands are small, triangular-shaped glands located on top of each kidney. They play a crucial role in the body\'s response to stress, metabolism, and the regulation of blood pressure, among other functions. The adrenal glands are divided into two main regions, each responsible for producing different hormones: the adrenal cortex and the adrenal medulla. ##### STRUCTURE OF THE ADRENAL GLAND **Adrenal Cortex** The outer layer of the adrenal gland, divided into three zones, each producing specific types of steroid hormones. Zona Glomerulosa (outermost layer): Produces mineralocorticoids, primarily aldosterone. Zona Fasciculata (middle layer): Produces glucocorticoids, primarily cortisol. Zona Reticularis (innermost layer): Produces androgens, including dehydroepiandrosterone (DHEA). **Adrenal Medulla** The inner core of the adrenal gland, composed of chromaffin cells that produce catecholamines, including adrenaline (epinephrine) and noradrenaline (norepinephrine). ##### HORMONES SECRETED BY THE ADRENAL CORTEX **[Mineralocorticoids (Aldosterone)]** **Production Site** Zona glomerulosa of the adrenal cortex. **Function** Regulation of Electrolytes and Water Balance Aldosterone plays a critical role in maintaining blood pressure and electrolyte balance by promoting sodium reabsorption and potassium excretion in the kidneys. This action increases water retention, thereby increasing blood volume and blood pressure. **Control of Release** Renin-Angiotensin-Aldosterone System (RAAS) Low blood pressure or low sodium levels trigger the release of renin from the kidneys, which leads to the production of angiotensin II. Angiotensin II stimulates aldosterone release. Potassium Levels High potassium levels directly stimulate aldosterone secretion. Feedback Mechanism As blood pressure and sodium levels normalize, aldosterone release decreases. **[Glucocorticoids (Cortisol)]** **Production Site** Zona fasciculata of the adrenal cortex. **Function** Stress Response Cortisol is often referred to as the \"stress hormone\" because it helps the body respond to stress by increasing blood glucose levels, enhancing the metabolism of fats, proteins, and carbohydrates, and suppressing inflammation and immune responses. Metabolism Cortisol promotes gluconeogenesis (the production of glucose from non-carbohydrate sources), particularly in the liver, and mobilizes fatty acids from adipose tissue. Immune Suppression Cortisol reduces inflammation by inhibiting the production of inflammatory cytokines and suppressing immune system activity. **Control of Release** Hypothalamic-Pituitary-Adrenal (HPA) Axis Corticotropin-Releasing Hormone (CRH) from the hypothalamus stimulates the anterior pituitary to release Adrenocorticotropic Hormone (ACTH). ACTH then stimulates the adrenal cortex to produce and release cortisol. **Feedback Mechanism** High levels of cortisol inhibit CRH and ACTH release through negative feedback, reducing cortisol production. **[Androgens (e.g., Dehydroepiandrosterone, DHEA)]** **Production Site** Zona reticularis of the adrenal cortex. **Function** Sex Hormones Although androgens are often associated with male characteristics, they are produced in both males and females. In females, adrenal androgens contribute to the development of secondary sexual characteristics and are precursors to estrogens. In males, their effect is less pronounced due to the higher levels of testosterone produced by the testes. Puberty Adrenal androgens play a role in the onset of puberty and the development of body hair. **Control of Release** ACTH Regulation The release of adrenal androgens is partially regulated by ACTH from the anterior pituitary. Feedback Mechanism While feedback regulation is more complex, increased levels of androgens can exert a feedback effect on the hypothalamic-pituitary axis. ##### HORMONES SECRETED BY THE ADRENAL MEDULLA **[Catecholamines (Adrenaline and Noradrenaline)]** **Production Site** Chromaffin cells in the adrenal medulla. **Function** Fight-or-Flight Response Adrenaline (Epinephrine) → Increases heart rate, dilates airways, and promotes the breakdown of glycogen to glucose in the liver, preparing the body for rapid action. Noradrenaline (Norepinephrine) → Primarily causes vasoconstriction, increasing blood pressure. It also works with adrenaline to increase heart rate and blood flow to muscles. Metabolic Effects Both adrenaline and noradrenaline increase blood glucose levels by stimulating glycogenolysis (the breakdown of glycogen to glucose) and lipolysis (the breakdown of fats). **Control of Release** Sympathetic Nervous System The release of catecholamines is directly controlled by the sympathetic nervous system in response to stressors, such as physical danger or emotional stress. **Feedback Mechanism** The release of catecholamines is part of a rapid, short-term response to stress and is not regulated by the typical feedback mechanisms that control other adrenal hormones. ##### INTEGRATION AND REGULATION **Stress Response** The adrenal glands are central to the body's response to stress, with the adrenal cortex producing cortisol for long-term stress adaptation and the adrenal medulla releasing catecholamines for immediate response. **Metabolic Regulation** Cortisol, aldosterone, and adrenaline all play roles in regulating metabolism and maintaining homeostasis, particularly in response to changing internal and external environments. ##### CLINICAL RELEVANCE **Cushing's Syndrome** Caused by excessive cortisol production, often due to a tumour in the adrenal gland (primary) or pituitary gland (secondary). **Addison's Disease** Characterized by insufficient production of adrenal hormones (both cortisol and aldosterone), leading to symptoms such as fatigue, low blood pressure, and hyperpigmentation. **Pheochromocytoma** A rare tumour of the adrenal medulla that leads to excessive production of catecholamines, causing high blood pressure, palpitations, and sweating. **PANCREAS** **TLO 2.5 --- DESCRIBE THE MAIN FUNCTIONS AND SECRETION OF HORMONES FROM THE PANCREAS INVOLVED IN BGL HOMEOSTASIS.** **STRUCTURE OF THE PANCREAS** The pancreas is located in the upper abdomen, behind the stomach. The endocrine component of the pancreas is composed of clusters of cells known as the **Islets of Langerhans**. These islets contain several types of hormone-producing cells: **ALPHA CELLS** **BETA CELLS** ---------------------- ----------------------------------------------- ---------------------- --------------------------------------------------- **Location** Scattered throughout the Islets of Langerhans **Location** Centrally located within the Islets of Langerhans **Hormone produced** Glucagon **Hormone produced** Insulin **DELTA CELLS** **PP CELLS (F CELLS)** **Location** Distributed within the Islets of Langerhans **Location** Primarily in the head of the pancreas **Hormone produced** Somatostatin **Hormone produced** Pancreatic polypeptide **HORMONES INVOLVED IN BGL HOMEOSTASIS** The primary hormones secreted by the pancreas that regulate blood glucose levels are **insulin** and **glucagon**. +-----------------------------------+-----------------------------------+ | **INSULIN** | | +===================================+===================================+ | **Produced By:** | Beta cells of the Islets of | | | Langerhans. | +-----------------------------------+-----------------------------------+ | **Function:** | **Lowers blood glucose levels** | | | | | | Insulin facilitates the uptake of | | | glucose from the bloodstream into | | | cells, particularly muscle and | | | fat cells, where it can be used | | | for energy or stored as glycogen. | +-----------------------------------+-----------------------------------+ | | **Promotes glycogenesis** | | | | | | Insulin stimulates the liver to | | | convert excess glucose into | | | glycogen for storage | | | (glycogenesis). | +-----------------------------------+-----------------------------------+ | | **Inhibits Glycogenolysis and | | | Gluconeogenesis** | | | | | | Insulin suppresses the breakdown | | | of glycogen into glucose | | | (glycogenolysis) and the | | | production of glucose from | | | non-carbohydrate sources | | | (gluconeogenesis) in the liver. | +-----------------------------------+-----------------------------------+ | | **Promotes Lipogenesis** | | | | | | Insulin encourages the conversion | | | of glucose into fatty acids and | | | triglycerides for long-term | | | energy storage in adipose tissue. | +-----------------------------------+-----------------------------------+ | **Control of release:** | **Blood Glucose Levels** | | | | | | Insulin secretion is directly | | | stimulated by rising blood | | | glucose levels after a meal. | +-----------------------------------+-----------------------------------+ | | **Incretins** | | | | | | Hormones like GLP-1 | | | (glucagon-like peptide-1) | | | released from the gut in response | | | to food intake also stimulate | | | insulin secretion. | +-----------------------------------+-----------------------------------+ | | **Feedback Mechanism** | | | | | | As blood glucose levels decrease | | | due to insulin's action, insulin | | | secretion is reduced through | | | negative feedback. | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **GLUCAGON** | | +===================================+===================================+ | **Produced By:** | Alpha cells of the Islets of | | | Langerhans. | +-----------------------------------+-----------------------------------+ | **Function:** | **Raises Blood Glucose Levels** | | | | | | Glucagon acts on the liver to | | | increase blood glucose levels by | | | stimulating glycogen breakdown | | | (glycogenolysis) and the | | | synthesis of glucose from | | | non-carbohydrate sources | | | (gluconeogenesis). | +-----------------------------------+-----------------------------------+ | | **Mobilizes Energy Stores** | | | | | | Glucagon promotes the breakdown | | | of fat stores (lipolysis) to | | | provide additional energy | | | substrates. | +-----------------------------------+-----------------------------------+ | **Control of release:** | **Blood Glucose Levels** | | | | | | Glucagon secretion is stimulated | | | by low blood glucose levels | | | (hypoglycaemia). | +-----------------------------------+-----------------------------------+ | | **Amino Acids** | | | | | | A high concentration of amino | | | acids in the blood after a | | | protein-rich meal can also | | | stimulate glucagon release. | +-----------------------------------+-----------------------------------+ | | **Feedback Mechanism** | | | | | | As blood glucose levels rise due | | | to glucagon's action, glucagon | | | secretion decreases through | | | negative feedback. | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **SOMATOSTATIN** | | +===================================+===================================+ | **Produced By:** | Delta cells of the Islets of | | | Langerhans. | +-----------------------------------+-----------------------------------+ | **Function:** | **Inhibits Hormone Secretion** | | | | | | Somatostatin inhibits the release | | | of both insulin and glucagon, | | | helping to fine-tune the balance | | | of these hormones and prevent | | | excessive fluctuations in blood | | | glucose levels. | +-----------------------------------+-----------------------------------+ | **Control of release:** | **Nutrient Levels** | | | | | | The release of somatostatin is | | | triggered by the presence of | | | glucose, amino acids, and fatty | | | acids in the bloodstream. | +-----------------------------------+-----------------------------------+ | | **Autocrine and Paracrine | | | Effects** | | | | | | Somatostatin acts locally within | | | the pancreas to modulate the | | | release of insulin and glucagon. | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **PANCREATIC POLYPEPTIDE (PP)** | | +===================================+===================================+ | **Produced By:** | PP cells (F cells) in the | | | pancreas. | +-----------------------------------+-----------------------------------+ | **Function:** | **Regulation of Pancreatic | | | Secretions** | | | | | | Pancreatic polypeptide helps | | | regulate the exocrine function of | | | the pancreas and may also play a | | | role in appetite regulation. | +-----------------------------------+-----------------------------------+ | **Control of release:** | **Nutrient Intake** | | | | | | The release of pancreatic | | | polypeptide is influenced by food | | | intake, particularly protein-rich | | | meals. | +-----------------------------------+-----------------------------------+ **INTEGRATION AND REGULATION OF BLOOD GLUCOSE LEVELS** **Fed State (Postprandial):** After a meal, blood glucose levels rise, leading to increased insulin secretion. Insulin facilitates glucose uptake by cells, promotes glycogen storage, and inhibits glucose production by the liver, thereby lowering blood glucose levels. **Fasting State:** During fasting, blood glucose levels drop, triggering the release of glucagon. Glucagon stimulates the liver to release stored glucose into the bloodstream, ensuring a steady supply of energy and preventing hypoglycaemia. **Exercise:** During physical activity, insulin levels decrease, and glucagon levels increase to maintain blood glucose levels and ensure that muscles have sufficient energy. **CLINICAL RELEVANCE** **Diabetes Mellitus** Type 1 Diabetes: An autoimmune condition where the body's immune system attacks and destroys beta cells, leading to little or no insulin production. This results in chronic hyperglycaemia. Type 2 Diabetes: A condition characterized by insulin resistance, where cells do not respond effectively to insulin. Over time, the pancreas cannot produce enough insulin to overcome this resistance, leading to elevated blood glucose levels. **Hypoglycaemia:** A condition where blood glucose levels fall below normal, leading to symptoms such as dizziness, confusion, and fainting. It can occur due to excessive insulin production or insulin therapy, especially in diabetic patients. **Hyperglycaemia:** A condition where blood glucose levels are abnormally high, often due to insufficient insulin action. Chronic hyperglycaemia is a hallmark of diabetes and can lead to serious complications like cardiovascular disease, neuropathy, and kidney damage. **PTH, CALCITONIN & VITAMIN D -- CALCIUM HOMEOSTASIS** **TLO 2.6 --- EXPLAIN THE ROLES OF PARATHYROID HORMONE (PTH), CALCITONIN AND VITAMIN D IN CALCIUM HOMEOSTASIS.** +-----------------------------------+-----------------------------------+ | **PARATHYROID HORMONE (PTH)** | | +===================================+===================================+ | **Produced By:** | The parathyroid glands, which are | | | four small glands located on the | | | posterior surface of the thyroid | | | gland. | +-----------------------------------+-----------------------------------+ | **Function:** | **Increases blood calcium | | | levels** | | | | | | PTH is the primary hormone | | | responsible for raising blood | | | calcium levels when they are too | | | low (hypocalcaemia). | +-----------------------------------+-----------------------------------+ | | **Bone resorption** | | | | | | PTH stimulates osteoclasts | | | (bone-resorbing cells) to break | | | down bone tissue, releasing | | | calcium and phosphate into the | | | bloodstream. | +-----------------------------------+-----------------------------------+ | | **Renal reabsorption of calcium** | | | | | | PTH increases calcium | | | reabsorption in the kidneys, | | | reducing the amount of calcium | | | excreted in urine. | | | | | | It also decreases phosphate | | | reabsorption in the kidneys, | | | which helps to maintain the | | | proper balance of calcium and | | | phosphate in the blood. | +-----------------------------------+-----------------------------------+ | | **Activation of vitamin D** | | | | | | PTH stimulates the conversion of | | | inactive vitamin D | | | 925-hydroxyvitamin D) to its | | | active form | | | (1,25-dihydroxyvitamin D, also | | | known as calcitriol) in the | | | kidneys. | | | | | | Active vitamin D enhances calcium | | | absorption from the kidneys. | +-----------------------------------+-----------------------------------+ | **Control of release:** | **Blood calcium levels** | | | | | | The secretion of PTH is directly | | | regulates by the level of calcium | | | in the blood. | | | | | | Low calcium levels stimulate the | | | release of PTH, leading to | | | hypercalcaemia (elevated blood | | | calcium levels). | +-----------------------------------+-----------------------------------+ | **Clinical relevance:** | **Hyperparathyroidism** | | | | | | A condition characterized by | | | excessive secretion of PTH, | | | leading to hypercalcemia | | | (elevated blood calcium levels). | | | | | | This can result in weakened | | | bones, kidney stones, and other | | | complications. | +-----------------------------------+-----------------------------------+ | | **Hypoparathyroidism** | | | | | | A condition where insufficient | | | PTH is produced, leading to | | | hypocalcaemia (low blood calcium | | | levels). | | | | | | This can cause muscle cramps, | | | tetany (involuntary muscle | | | contractions), and, in severe | | | cases, life-threatening | | | complications like cardiac | | | arrhythmias. | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **CALCITONIN** | | +===================================+===================================+ | **Produced By:** | The parafollicular cells (also | | | known as C cells) of the thyroid | | | gland. | +-----------------------------------+-----------------------------------+ | **Function:** | **Decreases blood calcium | | | levels** | | | | | | Calcitonin acts to lower blood | | | calcium levels when they are too | | | high (hypercalcaemia). | +-----------------------------------+-----------------------------------+ | | **Inhibition of bone | | | reabsorption** | | | | | | Calcitonin inhibits the activity | | | of osteoclasts, reducing the | | | breakdown of bone tissue and the | | | release of calcium into the | | | bloodstream. | +-----------------------------------+-----------------------------------+ | | **Calcium excretion** | | | | | | Calcitonin increases calcium | | | excretion by the kidneys, further | | | helping to lower blood calcium | | | levels. | +-----------------------------------+-----------------------------------+ | **Control of release:** | **Blood calcium levels** | | | | | | High blood calcium levels | | | stimulate the release of | | | calcitonin, while low calcium | | | levels inhibit its secretion. | | | | | | Calcitonin is primarily involved | | | in the short-term regulation of | | | calcium levels. | +-----------------------------------+-----------------------------------+ | **Clinical relevance:** | **Therapeutic use** | | | | | | Calcitonin is sometimes used as a | | | medication to treat conditions | | | like osteoporosis and Paget's | | | disease of bone, where excessive | | | bone resorption is a problem. | +-----------------------------------+-----------------------------------+ | | **Calcitonin deficiency** | | | | | | While calcitonin plays a role in | | | calcium homeostasis, its | | | deficiency typically does not | | | result in significant clinical | | | symptoms, as PTH and vitamin D | | | have more dominant roles in | | | long-term calcium regulation. | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | **VITAMIN D** | | +===================================+===================================+ | **Produced By:** | Vitamin D is obtained from the | | | diet and also synthesized in the | | | skin upon exposure to sunlight | | | (UVB radiation). | | | | | | It undergoes two hydroxylation | | | steps to become active: | +-----------------------------------+-----------------------------------+ | | **First** Hydroxylation Occurs in | | | the liver, converting vitamin D | | | to 25-hydroxyvitamin D | | | (calcidiol). | +-----------------------------------+-----------------------------------+ | | **Second** Hydroxylation Occurs | | | in the kidneys, converting | | | calcidiol to | | | 1,25-dihydroxyvitamin D | | | (calcitriol), the active form of | | | vitamin D. | +-----------------------------------+-----------------------------------+ | **Function:** | **Increases blood calcium | | | levels:** Active vitamin D | | | (calcitriol) enhances calcium | | | absorption from the intestines, | | | ensuring sufficient calcium is | | | available for various bodily | | | functions. | +-----------------------------------+-----------------------------------+ | | **Bone health:** Vitamin D | | | promotes the mineralization of | | | bone by ensuring adequate calcium | | | and phosphate levels in the | | | blood. | +-----------------------------------+-----------------------------------+ | | **Renal calcium reabsorption:** | | | Vitamin D also promotes calcium | | | reabsorption in the kidneys, | | | helping to conserve calcium and | | | maintain blood calcium levels. | +-----------------------------------+-----------------------------------+ | **Control of Activation:** | **PTH regulation:** PTH | | | stimulates the conversion of | | | inactive vitamin D to its active | | | form in the kidneys, particularly | | | when blood calcium levels are | | | low. | +-----------------------------------+-----------------------------------+ | | **Feedback Mechanism:** High | | | levels of active vitamin D can | | | inhibit further activation, | | | thereby maintaining a balance. | +-----------------------------------+-----------------------------------+ | **Clinical relevance:** | **Vitamin D deficiency** | | | | | | Insufficient vitamin D can lead | | | to rickets in children (softening | | | and weakening of bones) and | | | Osteomalacia in adults, both of | | | which are characterized by poor | | | bone mineralization. | +-----------------------------------+-----------------------------------+ | | **Osteoporosis** | | | | | | Adequate vitamin D is crucial for | | | preventing osteoporosis, a | | | condition where bones become | | | fragile and more prone to | | | fractures due to insufficient | | | calcium and phosphate. | +-----------------------------------+-----------------------------------+ | | **Hypervitaminosis D** | | | | | | Excessive vitamin D intake can | | | lead to hypercalcemia and | | | associated complications such as | | | kidney stones, calcification of | | | soft tissues, and impaired kidney | | | function. | +-----------------------------------+-----------------------------------+ **INTEGRATION OF PTH, CALCITONIN, AND VITAMIN D IN CALCIUM HOMEOSTASIS** **Low blood calcium levels:** When blood calcium levels drop, the parathyroid glands secrete PTH. PTH raises blood calcium levels by increasing bone resorption, enhancing calcium reabsorption in the kidneys, and activating vitamin D, which increases calcium absorption from the intestines. **High Blood Calcium Levels:** When blood calcium levels are high, calcitonin is released from the thyroid gland. Calcitonin lowers blood calcium levels by inhibiting bone resorption and increasing calcium excretion in the urine. **Role of Vitamin D:** Vitamin D is essential for absorbing dietary calcium and phosphate from the intestines. It ensures that the calcium obtained from the diet is sufficient to maintain bone health and meet the body\'s physiological needs. **CLINICAL IMPLICATIONS AND DISORDERS** **Calcium Homeostasis Disorders:** Disruptions in the balance of PTH, calcitonin, and vitamin D can lead to conditions like hypercalcemia, hypocalcaemia, osteoporosis, rickets, and Osteomalacia. **Aging and Calcium Regulation:** As individuals age, the ability to produce vitamin D from sunlight decreases, and the efficiency of calcium absorption from the intestines also declines. This can lead to an increased risk of osteoporosis and fractures in the elderly. **FUNCTION ALTERATION ACROSS THE LIFESPAN** **TLO 2.7 --- EXPLAIN HOW ENDOCRINE SYSTEM FUNCTION ALTERS ACROSS THE LIFESPAN.** The endocrine system undergoes significant changes throughout a person's life, from infancy through old age. These changes can impact the secretion and regulation of hormones, influencing growth, metabolism, reproduction, and overall health. **INFANCY AND CHILDHOOD** **Growth Hormone (GH) and Growth** **GH Secretion:** During infancy and childhood, the pituitary gland secretes high levels of growth hormone, which is crucial for promoting growth and development. **Thyroid Hormones:** Thyroid hormones (T3 and T4) are also critical during this stage, supporting growth, brain development, and metabolic regulation. **Insulin-Like Growth Factor (IGF-1):** GH stimulates the liver to produce IGF-1, which promotes bone and tissue growth. High levels of IGF-1 during childhood support rapid growth. **Adrenal Gland Function** **Adrenarche:** Around the age of 6-8 years, the adrenal glands begin to increase the production of androgens (e.g. DHEA), a process known as adrenarche. These androgens contribute to the development of secondary sexual characteristics during puberty. **Puberty** **Gonadal Hormones:** Puberty marks the onset of significant changes in endocrine function. The hypothalamus increases the secretion of gonadotropin-releasing hormone (GnRH), which stimulates the pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones, in turn, stimulate the gonads (testes in males, ovaries in females) to produce sex hormones (testosterone in males, estrogen and progesterone in females). **Secondary Sexual Characteristics** The increased secretion of sex hormones during puberty leads to the development of secondary sexual characteristics such as breast development, growth of body hair, and changes in body composition. **ADULTHOOD** **Reproductive Function** **Stable Hormone Levels:** During early adulthood, hormone levels generally stabilize. In females, estrogen and progesterone regulate the menstrual cycle, while testosterone maintains reproductive function and muscle mass in males. **Pregnancy:** In women, pregnancy leads to profound hormonal changes, including elevated levels of human chorionic gonadotropin (hCG), estrogen, progesterone, and prolactin. These hormones are essential for maintaining pregnancy and preparing the body for childbirth and lactation. **Metabolic Regulation** **Thyroid Function:** The thyroid gland continues to play a crucial role in regulating metabolism, body temperature, and energy levels. In some individuals, thyroid function may begin to decline with age, leading to conditions like hypothyroidism or hyperthyroidism. **Insulin Sensitivity:** Insulin secretion by the pancreas helps regulate blood glucose levels. In adulthood, insulin sensitivity may begin to decrease, particularly in individuals who are overweight or have a sedentary lifestyle, leading to an increased risk of type 2 diabetes. **Stress Response** **Cortisol:** The adrenal glands continue to produce cortisol, the body's primary stress hormone. Chronic stress in adulthood can lead to prolonged elevation of cortisol levels, which may contribute to health issues such as hypertension, obesity, and immune system suppression. **AGEING** **Decline in Hormone Production** **Menopause:** In women, menopause typically occurs between the ages of 45-55, marking the end of reproductive capacity. During menopause, the ovaries significantly reduce the production of estrogen and progesterone, leading to symptoms such as hot flashes, mood swings, and an increased ri