Chapter 18: Endocrine System PDF

Chapter 18: The Endocrine System **An Introduction to the Endocrine System** Endocrine cells and tissues produce about 30 different **[hormones]** (chemical messengers). - Hormones control and coordinate body processes. 18-1 Homeostasis is preserved through intercellular communication by the n...

Chapter 18: The Endocrine System **An Introduction to the Endocrine System** Endocrine cells and tissues produce about 30 different **[hormones]** (chemical messengers). - Hormones control and coordinate body processes. 18-1 Homeostasis is preserved through intercellular communication by the nervous and endocrine systems. **Mechanisms of Intercellular Communication** There are several mechanisms of intercellular communication... **[Direct communication:]** exchange of ions and molecules between adjacent cells across gap junctions between **two cells of the same type.** - Highly specialized and relatively rare. **[Paracrine communication:]** chemical signals transfer information from **cell to cell within a single tissue.** **[Autocrine communication:]** messages affect the **same cells that secrete them.** - **[Autocrine:]** the chemicals involved in autocrine communication. - Ex: *prostaglandins secreted by smooth muscle cells cause the same cells to contract.* **[Endocrine communication:]** cells release hormones that are transported in bloodstream. - Alters metabolic activities of many organs. **[Target cells:]** have receptors needed to bind and "read" hormonal messages. **[Hormones:]** chemical messengers. - Change types, quantities, or activities of enzymes and structural proteins in target cells. - Can alter metabolic activities of multiple tissues and organs at the same time. - Affect long-term processes like growth and development. **[Synaptic communication:]** neurons release neurotransmitters at a synapse. - Leads to action potentials that are propagated along axons. - Allows for high-speed "messages" to reach specific destinations. - Ideal for crisis management. **Comparisons of Endocrine and Nervous Communication** **BOTH** endocrine and nervous systems... - Rely on release of chemicals that bind to specific receptors on target cells. - Share chemical messengers such as, norepinephrine and epinephrine. - Regulated mainly by negative feedback. - Function to preserve homeostasis by coordinating and regulating activities. The endocrine system includes all endocrine cells and tissues that produce hormones or paracrines. - Endocrine cells release secretions into extracellular fluid. - Unlike exocrine cells. - Endocrine organs are scattered throughout body. 18-2 The endocrine systemphysiological procoesses by releasing bloodborne hormones that bind to receptors on remote target organs. **[Classes of Hormones]** There are 3 classes of homrones: amino acid derivatives, peptide hormones, and lipid derivatives. **[1.Amino Acid Derivatives (Biogenic Amines)]** - Small molecules structurally related to amino acids. Amino acid derivative hormones can either be synthesized from tyrosine or tryptophan. **Derivatives of [tyrosine]** - Thyroid hormones. - Catecholamines (epinephrine, norepinephrine, and dopamine). **Derivatives of [tryptophan]** - Serotonin and melatonin. **[2. Peptide Hormones]** - Chains of amino acids. - Most are synthesized as **[prohormones]**. - Inactive molecules converted to active hormones before or after they are secreted. We can divide peptide hormones into 2 groups: glycoproteins and short polypeptides/small proteins. **Glycoproteins** - Proteins more than 200 amino acids long that have carbohydrate side chains Ex. *TSH, LH, FSH.* **Short Polypeptides** - ADH and OXT are each 9 amino acids long. **Small Proteins** - Insulin (51 amino acids). - GH (191 amino acids). - PRL (198 amino acids). Includes all hormones secreted by hypothalamus, heart, thymus, digestive tract, pancreas, posterior lobe of the pituitary gland, etc. **[3.Lipid Derivatives]** There are 2 groups of lipid derivatives: eicosanoids and steroid hormones. **Eicosanoids** **[Eicosanoids:]** a signaling molecule, derived from **[arachidonic acid]**, a 20-carbon fatty acid. Eicosanoids include... - Leukotrienes. - **[Prostaglandins:]** coordinate local cellular activities. - Thromboxanes. - Prostacyclins. **Steroid Hormones** **[Steroid hormones:]** derived from cholesterol. - Bound to specific transport proteins in the plasma. - Remain in circulation longer than peptide hormones. Steroid hormones include... - Androgens from testes in males. - Estrogens and progesterone from ovaries in females. - Corticosteroids from adrenal cortex. - Calcitriol from kidneys. **Transport and Inactivation of Hormones** Hormones may circulate freely, or travel bound to special carrier proteins. - Free hormones remain functional for less than an hour and are inactivated when they... - Diffuse out of bloodstream and bind to receptors on target cells. - Absorbed and broken down by liver or kidneys. - Broken down by enzymes in blood or interstitial fluids. - Thyroid and steroid hormones. - Remain functional much longer. - More than 99 percent become attached to special transport proteins in blood. - Equilibrium state exists between free and bound forms. - Bloodstream contains a substantial reserve of bound hormones. **Mechanisms of Hormone Action** Binding of a hormone may... - Alter genetic activity. - Alter rate of protein synthesis. - Change membrane permeability. To affect a target cell, a hormone must FIRST interact with an appropriate receptor... **[Hormone receptor:]** protein molecule to which a particular molecule binds strongly. - Different tissues have different combinations of receptors. - Presence or absence of a specific receptor determines hormonal sensitivity of a cell. The presence or absence of a hormone can also affect the nature and number of hormone receptor proteins. **[Down-regulation:]** presence of a hormone triggers a [decrease] in the number of hormone receptors. - When levels of a particular hormone are **[HIGH]**, cells become **[LESS]** sensitive to it. **[Up-regulation:]** absence of a hormone triggers an [increase] in the number of hormone receptors. - When levels of a particular hormone are **[LOW]**, cells become **[MORE]** sensitive to it. Hormone receptors are either located on the plasma membrane (extracellular response) or within target cells (intracellular response). These different types of receptors respond with different mechanisms. **Extracellular Receptors** - Catecholamines and peptide hormones are... - Not lipid soluble. - Unable to penetrate plasma membrane. - Bind to receptor proteins on outer surface of plasma membrane (extracellular receptors). **Intracellular Receptors** - Steroid and thyroid hormones are... - Lipid soluble. - Diffuse across plasma membrane and bind to receptors inside cell (intracellular receptors). **Hormones and Extracellular Receptors: Second Messengers** **[First messenger:]** hormone that binds to extracellular receptor. - Promotes release of second messenger in cell. **[Second messenger:]** intermediary molecule that appears due to hormone--receptor interaction. - May act as enzyme activator, inhibitor, or cofactor. - Results in change in rates of metabolic reactions. - Example: cAMP, cGMP, Ca^2+^. **Process of Amplification** - When a small number of hormone molecules binds to extracellular receptors, thousands of second messengers may appear. - Magnifies effect of hormone on target cell. **G-proteins and cAMP** **[G-protein:]** enzyme complex coupled to membrane receptor. - Protein binds GTP. - Involved in link between first messenger and second messenger. The steps involved in increasing cAMP level, which accelerates metabolic activity of cell... 1. Activated G protein activates **adenylate cyclase**. 2. Adenylate cyclase converts ATP to **cyclic AMP (cAMP)**. 3. cAMP functions as a second messenger. 4. Generally, cAMP activates kinases that phosphorylate proteins. Increase in cAMP level is usually short-lived. - **Phosphodiesterase (PDE)** converts cAMP to AMP. **G-proteins and Ca^2+^** 1. G protein activates **phospholipase C** (**PLC**). 2. Triggers receptor cascade beginning with production of **diacylglycerol** (**DAG**) and **inositol** **triphosphate** (**IP~3~**) from phospholipids. 3. IP**~3~** diffuses into cytoplasm and triggers release of Ca^2+^ from intracellular reserves. 4. Calcium ion channels open due to activation of **protein kinase C** (**PKC**), and Ca^2+^ enters cell. 5. Ca^2+^ binds to **calmodulin**, activating enzymes. **Hormones and Intracellular Receptors** - Steroid hormones can alter rate of DNA transcription in nucleus. - Alterations in synthesis of enzymes or structural proteins. - Directly affect activity and structure of target cell. - Thyroid hormones bind to receptors within nucleus and on mitochondria. - Activate genes or change rate of transcription. - Increase rates of ATP production. **Control of Hormone Secretion** Hormone secretion is [mainly controlled] by **negative feedback**. - Stimulus triggers production of hormone that reduces intensity of the stimulus. - May only involve one hormone. - Can be triggered by... - **[Humoral stimuli]** (change in extracellular fluid) - **[Hormonal stimuli]** (arrival or removal of hormone) - **[Neural stimuli]** (neurotransmitters) **[Humoral stimuli:]** control hormone secretion by heart, pancreas, parathyroid gland, and digestive tract. **[Hormonal stimuli:]** may involve one or more intermediary steps. - Two or more hormones involved. **[Neural stimuli:]** hypothalamus provides highest level of control. 18-3 The anterior lobe of the pituitary gland produces and releases hormones under hypothalamic control, while the posterior lobe releases hypothalamic hormones. **[PITUITARY GLAND (Hypophysis)]** - Lies within sella turcica. - Sellar diaphragm isolates pituitary gland from cranial cavity. - Hangs inferior to **[hypothalamus]**. - Connected by infundibulum. - Releases nine important peptide hormones. - Bind to extracellular receptors. - Use cAMP as second messenger. **[HYPOTHALAMUS]** - Regulates functions of the pituitary gland. - Synthesizes ADH and OXT and transports them to posterior pituitary gland for release. - Secretes **[regulatory hormones]** that control secretory activity of anterior pituitary gland. - Contains autonomic centers that exert direct control over adrenal medulla. The hypothalamus divides into two lobes: **[the anterior lobe (*adenohypophysis*)]** and the **[posterior lobe (*neurohypophysis*)]**. **The Anterior Lobe of the Pituitary Gland** - Also called **[adenohypophysis] because it is made from epithelial glandular tissue** - Hormones "turn on" endocrine glands or support functions of other organs. **Portal Vessels** - Blood vessels that link two capillary networks that are not primarily for delivery of oxygen and removing wastes. - Entire complex is called a portal system. **[Hypothalamic-Hypophyseal portal system:]** ensures that regulatory hormones from the hypothalamus reach cells in anterior pituitary before entering general circulation. **Hypothalamic Control of Anterior Lobe** Two classes of hypothalamic regulatory hormones: releasing hormones and inhibiting hormones. **[Releasing hormones (RH):]** stimulate synthesis and secretion of one or more hormones at anterior lobe. **[Inhibiting hormones (IH):]** prevent synthesis and secretion of hormones from anterior lobe. Rate of secretion is controlled by negative feedback. **Hormones of Anterior Pituitary Lobe** - **[Thyroid-stimulating hormone (TSH)]** - **[Adrenocorticotropic hormone (ACTH)]** - Released due to **[corticotropin-releasing hormone (CRH)]** - **[Prolactin (PRL)]** - Release inhibited by **[prolactin-inhibiting hormone (PIH)]** - Release stimulated by **[prolactin-releasing hormone (PRH)]** - **[Growth hormone (GH)]**, or somatotropin - Gonadotropins - **[Follicle-stimulating hormone (FSH)]** - **[Luteinizing hormone (LH)]** - In females, it induces ovulation and stimulates secretion of estrogens and progesterone. - In males, it stimulates production of androgens. - Production of FSH and LH is stimulated by **[gonadotropin-releasing hormone (GnRH)]** - **[Hypogonadism:]** caused by low production of gonadotropins. **[Growth hormone (GH)]** stimulates... - Liver cells to release **[somatomedins]** that stimulate tissue growth. - Somatomedins cause skeletal muscle fibers and other cells to increase uptake of amino acids. - Stem cells in epithelia and connective tissues to divide. - Breakdown of triglycerides in adipocytes, which leads to **[glucose-sparing effect]**. - Breakdown of glycogen by liver cells causing **[diabetogenic effect]**. Production of growth hormone is regulated by... - **[Growth hormone--releasing hormone (GH--RH)]** - **[Growth hormone--inhibiting hormone (GH--IH)]** **Pars Intermedia** - Secretes **[melanocyte-stimulating hormone (MSH)]** - Stimulates melanin production. Virtually nonfunctional in adults except in... - Pregnant women - Those with certain diseases **Posterior Lobe of the Pituitary Gland** - Also called **[neurohypophysis] because it is made of neural tissue** - Contains unmyelinated axons/terminals of hypothalamic neurons storing neurohormones in vesicles. - Hypothalamus manufactures two neurohormones: - **[Antidiuretic hormone (ADH)]** - **Helps regulate fluid balance by acting on the kidney and by initiating thirst** - **[Oxytocin (OXT)]** - Stimulates contraction of uterus during labor. - Promotes ejection of milk after delivery. 18-4 The thyroid gland synthesizes thyroid hormones that affect rate the rate of metabolism. **[THYROID GLAND]** - Lies inferior to thyroid cartilage of larynx. - Consists of two **lobes** connected by narrow **isthmus**. - **Thyroid** **follicles** - Hollow spheres lined by cuboidal epithelium. - Surrounded by capillaries. - Cells absorb **iodide ions** (**I^--^**) from blood. - **Follicle** **cavity** contains viscous colloid. - **C** (**clear**) **cells**, or parafollicular cells **Thyroglobulin** - Globular protein synthesized by follicle cells. - Secreted into colloid of thyroid follicles. - Contains the amino acid, **[tyrosine]** - The building block of thyroid hormones. **Thyroid hormones** - **[Thyroxine (T4)]**, or tetraiodothyronine - Contains four iodine atoms. - **[Triiodothyronine (T3)]** - Contains three iodine atoms. **Thyroid-binding globulins (TBGs)** - Proteins that bind about 75 percent of T4 and 70 percent of T3 entering the bloodstream. - Transthyretin and albumin - Bind most of the remaining thyroid hormones. - About 0.3 percent of T3 and 0.03 percent of T4 remain unbound and free to diffuse into tissues. **Thyroid-stimulating hormone (TSH)** - Absence causes thyroid follicles to become inactive. - Neither synthesis nor secretion occurs. - Binds to plasma membrane receptors. - Activates key enzymes in thyroid hormone production. Thyroid hormones affect almost every cell in body. - Enter target cells by transport system - Bind to receptors - In cytoplasm - On surfaces of mitochondria - In nucleus - In children, essential to normal development of skeletal, muscular, and nervous systems. Thyroid hormones activate genes involved in glycolysis and ATP production. - Results in **[calorigenic effect]**. - Increased energy consumption and heat generation of cells. - Responsible for strong, immediate, and short-lived increase in rate of cellular metabolism. **[C cells:]** produce calcitonin (CT). - Helps regulate concentrations of Ca2+ in body fluids. - Stimulates Ca2+ excretion by kidneys. - Prevents Ca2+ absorption by digestive tract. **Effects of thyroid hormones** - Elevate oxygen and energy consumption; in children, may cause rise in body temperature. - Increase heart rate and force of contraction. - Increase sensitivity to sympathetic stimulation. - Maintain normal sensitivity of respiratory centers to oxygen and carbon dioxide concentrations. - Stimulate red blood cell formation. - Stimulate activity in other endocrine tissues. - Accelerate turnover of minerals in bone. 18-5 The four parathyroid glands secrete parathyroid hormone, which increases the blood calcium ion level. **[PARATHYROID GLANDS ]** - Two pairs. - Embedded in posterior surface of thyroid gland. - Altogether, the four glands weigh 1.6 g. Parathyroid hormone (PTH), or parathormone - Secreted by parathyroid (principal) cells in response to low concentrations of Ca2+ in blood. - **Antagonist for calcitonin**. Major effects of parathyroid hormone - Stimulates osteoclasts. - Accelerates mineral turnover and Ca2+ release. - Enhances reabsorption of Ca2+ by kidneys, reducing urinary losses. - Stimulates formation and secretion of calcitriol by kidneys. **[ADRENAL GLANDS]** 18-6 The paired adrenal glands secrete several hormones that affect electrolyte balance and stress responses. - Lie along superior border of each kidney. **Superficial adrenal cortex** - Stores lipids, especially cholesterol and fatty acids. - Manufactures steroid hormones (**corticosteroids**). **Inner adrenal medulla** - Secretory activities controlled by sympathetic division of ANS. - Produces epinephrine and norepinephrine (**catecholamines**). **Adrenal cortex** - Subdivided into three zones... - Outer zona glomerulosa - Middle zona fasciculata - Inner zona reticularis **Zona glomerulosa (SALT)** - Outer region of adrenal cortex - Produces mineralocorticoids. Ex. *aldosterone* - Stimulates conservation of sodium ions and elimination of potassium ions - Increases sensitivity of salt receptors in taste buds - Secreted in response to... - Drop in blood Na+, blood volume, or blood pressure - Rise in blood K+ concentration **Zona fasciculata (SUGAR)** - Produces glucocorticoids. Ex. *cortisol, corticosterone, and cortisone* - Secretion is regulated by negative feedback Glucocorticoids have inhibitory effect on production of... - Corticotropin-releasing hormone (CRH) in hypothalamus - ACTH in anterior pituitary - Effects of glucocorticoids - Accelerate glucose synthesis and glycogen formation, especially in liver - Have anti-inflammatory effects - Inhibit activities of white blood cells and other components of immune system **Zona reticularis (SEX)** - Branching network of endocrine cells - Forms narrow band bordering each adrenal medulla - Produces small quantities of androgens under stimulation by ACTH - Some are converted to estrogens in bloodstream - Stimulate development of pubic hair before puberty **Adrenal medulla (ADRENALINE)** - Contains two types of secretory cells... - One produces epinephrine (E). - 75--80 percent of medullary secretion. - The other produces norepinephrine (NE). - 20--25 percent of medullary secretion. Results of activation of adrenal medulla - In skeletal muscles, E and NE trigger mobilization of glycogen reserves. - And accelerate breakdown of glucose. - In adipose tissue, stored fats are broken down into fatty acids. - In the liver, glycogen molecules are broken down. - In the heart, stimulation of β1 receptors speeds and strengthens cardiac muscle contraction. 18-7 The pineal gland secretes melatonin, which affects the circadian rhythm. - Lies in posterior portion of roof of third ventricle. - Contains [ **pinealocytes**]. - Synthesize hormone **[melatonin]**. **Functions of melatonin** - Influence circadian rhythms. - Inhibit reproductive functions. - Protect against damage by free radicals. **[PANCREAS]** 18-8 The pancreas is both an exocrine organ and an endocrine gland that produces hormones affecting the blood glucose level. - Large gland. - Lies in loop between inferior border of stomach and proximal portion of small intestine. - Mostly retroperitoneal. - Contains exocrine and endocrine cells. **Exocrine Pancreas** - Consists of clusters of gland cells called pancreatic acini and their attached ducts. - Takes up roughly 99 percent of pancreatic volume. - Gland and duct cells secrete alkaline, enzyme-rich fluid. - Passes through a network of ducts to lumen of digestive tract. **Endocrine Pancreas** - Consists of cells that form clusters known as **[pancreatic islets (*islets of Langerhans*)]**. - **[Alpha (α) cells]** produce **glucagon**. - **[Beta (β) cells]** produce **insulin**. - **[Delta (δ) cells]** produce peptide hormone identical to GH--IH (somatostatin). - **[Pancreatic polypeptide cells (PP cells)]** produce pancreatic polypeptide (PP). When blood glucose level increases... - Beta cells secrete insulin. - Stimulating transport of glucose into target cells. When blood glucose level decreases... - Alpha cells secrete glucagon. - Stimulating glycogen breakdown and glucose release by liver. **Insulin** - Released by beta cells. - Effects on target cells... - Accelerating glucose uptake. - Accelerating glucose use and enhancing ATP production. - Stimulating glycogen formation. - Stimulating amino acid absorption and protein synthesis. - Stimulating triglyceride formation in adipocytes. **Glucagon** - Released by alpha cells. - Mobilizes energy reserves. - Effects on target cells... - Stimulating breakdown of glycogen in skeletal muscle fibers and liver cells. - Stimulating breakdown of triglycerides in adipocytes. - Stimulating production and release of glucose in liver cells (gluconeogenesis). **[Hyperglycemia:]** abnormally high glucose levels in the blood. **[Diabetes mellitus:]** characterized by high glucose concentrations that overwhelm reabsorption capabilities of kidneys. - Glucose appears in urine. **[Polyuria:]** urine volume becomes excessive. **Type 1 diabetes mellitus** - Characterized by inadequate insulin production by pancreatic beta cells. - Patients require daily injections or continuous infusion of insulin. - Approximately 5 percent of cases. - Usually develops in children and young adults. **Type 2 diabetes mellitus** - **\*\*\* Most common form \*\*\*** - Usually, normal amounts of insulin are produced, at least initially. - **[Insulin resistance:]** tissues do not respond properly. - Associated with obesity. - Weight loss can be an effective treatment. Complications of untreated or poorly managed diabetes mellitus include... - Kidney degeneration. - Retinal damage (diabetic retinopathy). - May lead to blindness. - Early heart attacks (3--5 times more likely). - Peripheral nerve problems (diabetic neuropathies). - Peripheral tissue damage due to reduced blood flow. - Tissue death, ulceration, infection, and amputation. **[OTHER ENDOCRINE ORGANS]** 18-9 Many organs have secondary endocrine functions. **Organs with secondary endocrine functions** - Intestines (digestive system) - Kidneys (urinary system) - Heart (cardiovascular system) - Thymus (lymphatic system) - Gonads (reproductive system) **Intestines** - Release hormones that coordinate digestive activities. **Kidneys** - Release the hormones **[calcitriol]** and **[erythropoietin (EPO)]**. - Release the enzyme **[renin]**. - Renin converts **[angiotensinogen]** to **[angiotensin I]**. - In the lungs, **[angiotensin-converting enzyme]** converts angiotensin I to **[angiotensin II]**. **Heart** - Produces **[natriuretic peptides (ANP and BNP)]**. - When blood volume becomes excessive. - Actions opposes those of angiotensin II. - Resulting in reduction in blood volume and blood pressure. **Thymus** - Produces **[thymosin]** (blend of several hormones). - Promotes development and maturation of lymphocytes. **Testes** - **[Interstitial endocrine cells:]** produce androgens. - **[Testosterone]** is an important androgen. - **[Nurse cells (Sertoli cells):]** support differentiation and physical maturation of sperm. - Secrete inhibin for negative feedback. **Ovaries** - Produce **[estrogens]**. - Principal estrogen is **[estradiol]**. - After ovulation, follicle cells. - Reorganize into corpus luteum. - Release estrogens and progesterone. **Adipose tissue** - Produces **[leptin]**. - Provides feedback control of appetite. - Maintains normal levels of GnRH and gonadotropin synthesis. 18-10 Hormones interact over our lifetime to produce coordinated physiological responses. When a cell receives instructions from two hormones at the same time, four outcomes are possible. **[Antagonistic effect:]** result depends on balance between two hormones. **[Synergistic effect:]** additive effect. **[Permissive effect:]** one hormone is needed for another to produce effect. **[Integrative effect:]** hormones produce different but complementary results. **Hormones important to growth** - Growth hormone - Thyroid hormones - Insulin - Parathyroid hormone and calcitriol - Reproductive hormones **Growth hormone (GH)** - In children... - Supports muscular and skeletal development. - In adults... - Maintains normal blood glucose concentrations. - Mobilizes lipid reserves. **Thyroid hormones** - If absent during fetal development or for first year after birth... - Nervous system fails to develop normally. - Developmental delay results. - If T4 concentrations decline before puberty... - Normal skeletal development does not continue **Insulin** - Allows passage of glucose and amino acids across plasma membranes. - Important for growing cells. **Parathyroid hormone (PTH) and calcitriol** - Promote absorption of calcium salts from bloodstream for deposition in bone. - Inadequate levels result in weak, flexible bones. **Reproductive hormones** Androgens in males, estrogens in females. - Stimulate cell growth and differentiation in target tissues. - Produce gender-related differences in. - Skeletal proportions. - Secondary sex characteristics. **[Stress:]** any condition that threatens homeostasis. **[General adaptation syndrome (GAS), *stress response*:]** how body responds to stress-causing factors. - Divided into three phases... - Alarm phase - Resistance phase - Exhaustion phase **Alarm phase** - Immediate response to stress. - Directed by sympathetic division of ANS. - Energy reserves (mainly glucose) are mobilized. - Body prepares "fight or flight" responses. - **Epinephrine is dominant hormone**. **Resistance phase** - Occurs if stress lasts longer than a few hours. - May last for weeks or months. - Lipids and amino acids are mobilized for energy. - Glucose is conserved for use by nervous tissue. - **Glucocorticoids are dominant hormones**. **Exhaustion Phase** - Begins when homeostatic regulation breaks down. - Drop in K+ levels due to aldosterone produced in resistance phase. - Failure of one or more organ systems will be fatal. **Hormone changes** - Can affect behavior, intellectual capabilities, memory, learning, and emotional states. **Few functional changes occur with age** - Reproductive hormones decline in concentration. Some endocrine tissues become less responsive to stimulation