The Endocrine System 1-3 PDF

**The Endocrine System 1-3** **Outline of Lectures** - General principles of endocrine function - Types of hormones & signalling pathways or mechanisms - Broad divisions of the endocrine system - The central endocrine glands & their hormones - The peripheral endocrine glands & their...

**The Endocrine System 1-3** **Outline of Lectures** - General principles of endocrine function - Types of hormones & signalling pathways or mechanisms - Broad divisions of the endocrine system - The central endocrine glands & their hormones - The peripheral endocrine glands & their hormones **Learning Outcomes** - Give a general description of the basic principles of endocrine signalling - Describe the major divisions of the endocrine system - Give a detailed account of the major hormones of the central endocrine glands & their actions - Give a detailed account of the major hormones of the peripheral endocrine glands & their actions - Predict what might happen during over- or under- secretion of the major hormones **General Principles of Endocrine Function** **The Endocrine System** - Consists of specialised ductless glands (and neurosecretory cells) scattered throughout body - Glands/cells secrete biologically active chemical messengers (hormones) into the blood stream - The hormones are carried in the blood stream to interact with distant target cells - Interaction leads to specific target cell response in terms of metabolism, growth or reproduction A diagram of a person\'s body Description automatically generated **Functions of the Endocrine System** - One of the body's two major regulatory systems mainly about maintaining homeostasis - Regulates, integrates, coordinates & controls important cellular, organ & body functions - Cellular metabolism, and water & electrolyte balance - Cell growth, development and reproduction - Adaptive changes to help the body cope with stressful situations - Control & integration of the circulatory & digestive systems **The Endocrine System** - Chemical Classification of Hormones a. Amines & Amino Acid derivatives - **NA** noradrenaline**, AD** adrenaline**, DA** dopamine**, melatonin,** **T3 & T4** iodinated thyroxine b. Polypeptides, Proteins & Glycoproteins - **TRH, ADH, GH, FSH, insulin** c. Steroids -- derived from cholesterol - **Cortisol, testosterone, oestradiol, progesterone** - **Hydrophilic** all thyroid hormones -- dissolve in blood vs **Lipophilic** less soluble in blood -- carrying hormones in aqueous medium hormones **Synthesis and Transport of Hormones** - **Synthesis** a. Vesicle-mediated pathway - Synthesised in rER & packaged in secretory vesicles - **polypeptide / protein hormones** b. Non-vesicle-mediated pathway - Synthesised in sER & directly released - **steroid hormones** - **Transport** - Free & unbound hydrophilic / biologically active -- **peptide hormones & amines** - **Carrier** protein-bound lipophilic -- **steroid & thyroid hormones** ㄴusually bind to plasma protein called **GLOBULIN** -- also can interact with the drug -- displace the protein binding with bound hormones → more free hormones / increase the biological activity on target cell Ex) **Aspirin** -- highly protein-bound, competing with thyroid hormones -- reduce the effect of the drug ? **DYNAMIC EQUILIBRIUM** exists between free -- bound hormones **Control of Hormonal Secretion** - **Timing/Pattern of secretion** - Pulsatile or cyclical -- **diurnal or circadian rhythm**  release cortisol at night/C level drops during the day - **Negative feedback control** - End-product inhibition 1. Glands release the hormone 2. Stimulus/trigger increases the secretion of hormones 3. The level of the hormones will be increased to the normal state 4. Feedback to the glands - there's enough hormones in bloodstream -- stop secreting the hormones 5. DONE ! **Hormonal Signalling** - Hormones produce their effects on target cells by interacting with specific receptors - Target cell receptors are linked to specific effector systems in the cell - Two broad types of hormonal receptors: a. Cell surface receptors located outside of the PM -- hormone can be either hydrophilic/lipophilic ! - **Receptor-ion channels** - **G-protein coupled receptors** - **Tyrosine kinase-linked receptors** b. Intracellular or nuclear receptors located in the nucleus -- need to get in to bind with this receptor **Endocrine Disorders** - May result from: a. Hyposecretion - Endocrine gland secretes **[too little]** of its hormone - **Primary** T3 & T4 ↓**, Secondary and Tertiary** b. Hypersecretion - Endocrine gland secretes **[too much]** of its hormone - **Primary, Secondary, and Tertiary** c. Abnormal Target Cell Responsiveness - Receptor down-regulation - Receptor up-regulation **The Endocrine System** - **Two** broad anatomical divisions a. **The Central Endocrine Glands** located in the brain - **Hypothalamus** - **Pituitary gland** - **Pineal gland** b. **The Peripheral Endocrine Glands** located outside the brain - **Thyroid glands** - **Adrenal glands** - **Endocrine pancreas** - **Parathyroid glands** - **The Gonads (ovaries & testes)** sex glands **The Central Endocrine Glands** **The Hypothalamus & Pituitary Gland** work together quite intimately - Both located in the **diencephalon** middle part of the brain - Function cooperatively as 'master regulators' of the endocrine system **⇒ control of critical homeostatic & metabolic functions** - Both structures connected - By blood flow via the **hypophyseal portal system** (**hypothalamus** ⇒ **anterior** **pituitary**) - Via the **hypothalamo-hypophyseal nerve tract** (**hypothalamus** ⇒ **posterior** **pituitary**)  Diagram of a human body with blood vessels and arteries Description automatically generated with medium confidence **The Hypothalamus** - Brain's coordinating centre for endocrine, behavioural & autonomic nervous system function - Acts as neuroendocrine transducer or bridge 1. Receives & integrates multiple brain signals 2. Converts the electrical signals into chemical messages 3. Releases chemical messengers (hormones) to control secretion of pituitary hormones ⇒ **pituitary hormones control the activity of peripheral endocrine glands** **Hypothalamic Hormones** - Hormones that regulate anterior pituitary secretions - **Stimulatory** release to secrete hormones a. Growth hormone-releasing hormone (GHRH) b. Thyrotropin-releasing hormone (TRH) c. Corticotropin-releasing hormone (CRH) d. Gonadotropin-releasing hormone (GnRH) - **Inhibitory** reduce the secretion of hormones a. Somatostatin (Growth hormone-inhibiting hormone; GHIH) b. Dopamine (Prolactin-inhibiting hormone; PIH) **REMEMBER THIS PROCESS ! -- TROPIC ACTION ?** 1. Hypothalamus makes releasing hormones 2. They are sent to the anterior pituitary 3. The anterior pituitary releases its stored tropic hormones into the systemic circulation 4. They tell other endocrine organs in the body to grow & secrete their hormones **The Major Hypothalamic Hormones** A table with black text and white text Description automatically generated **Hypothalamic Hormones** - Hormones that are transported & stored in the posterior pituitary - **Vasopressin or Antidiuretic hormone (ADH)** - **Oxytocin** **The Pituitary Gland** - Hypophysis (growing under hypothalamus) -- located in diencephalon - The 'Master Gland' -- secretes hormones that control the function of many target glands & cells - Consists of **two** anatomically & functionally distinct lobes a. Anterior pituitary (Adenohypophysis) ic glandular pituitary glands - **Secretes & releases 6 major hormones** b. Posterior pituitary (Neurohypophysis) - **Stores & releases 2 hormones** Diagram of the internal organs of the human body Description automatically generated NO MSH **Anterior Pituitary Hormones** - **Growth Hormone (GH, somatotropin)** - Primary hormone for regulation of overall **body growth** mediates regular functions a. Stimulates growth of soft tissues & bone b. Stimulates cell division & protein synthesis **⇒ tissue hyperplasia** increase cell division **& hypertrophy** increase in cell size mainly because of protein synthesis c. Promotes cartilage & bone growth (in length & thickness) d. Growth-promoting effects are mediated via **stimulated release of insulin-like growth factors (IGFs)** or **somatomedins by the liver** - Important role in **intermediary** **metabolism** a. Exerts largely anti-insulin effects b. Increases lipolysis **⇒** **↑ free fatty acid (FFA) mobilisation & use as fuel** c. Inhibits peripheral cellular glucose uptake **⇒ ↑ blood glucose levels and ↓ use of glucose as** **fuel** - Secretion modulated by a. **GHRH & somatostatin from hypothalamus** b. **Ghrelin from gastric fundus** **Functions of Growth Hormone**  **GH -- Control of Release & Functions** Diagram of growth hormone Description automatically generated **The Endocrine System 2** **Anterior Pituitary Hormones** - **Thyroid-stimulating hormone (TSH)** - Promotes vascularisation & growth of the thyroid gland - Stimulates secretion of thyroid hormones - Secretion stimulated by TRH from hypothalamus - **Adrenocorticotropic hormone (ACTH)** - Controls growth of the adrenal cortex - Stimulates secretion of cortisol by adrenal cortex - Secretion stimulated by CRH from hypothalamus - **Follicle-stimulating hormone (FSH)** - Stimulates growth & development of ovarian follicles (F) - Promotes ovarian secretion of oestrogen (F) - Required for sperm production (M) - Secretion stimulated by GnRH from the hypothalamus - **Luteinizing hormone (LH)** - Responsible for ovulation & development of the corpus luteum (F) - Regulates ovarian secretion of sex hormones (F) - Stimulates testes to secrete testosterone (M) - Secretion stimulated by GnRH from hypothalamus - **Prolactin (PRL)** - Enhances breast development & milk production (F) - Secretion inhibited by DA dopamine from hypothalamus A table with text on it Description automatically generated **Posterior Pituitary Hormones** - **Vasopressin** - Antidiuretic hormone (ADH) - Regulates urinary H2O loss & water balance in the body - Promotes renal water re-absorption **⇒ regulation of plasma volume & osmotic pressure** - **Oxytocin** - Stimulates uterine contraction during childbirth & milk ejection during breast-feeding - Secretion stimulated by birth canal & breast suckling reflexes **The Pineal Gland** - Tiny, pinecone-shaped gland -- located in diencephalon - Secretes **melatonin** -- 'hormone of darkness' - Production stimulated by suprachiasmatic nucleus (SCN) -- **body's master 'biological clock'** - **Main functions:** - Synchronizes body's circadian rhythms with the 24 hours 'day-night' or 'light-dark' cycle - Promotes sleep - Influences reproductive activity -- onset of puberty melatonin secretion decreases ? A diagram of a brain Description automatically generated **The Peripheral Endocrine Glands** **The Thyroid Gland** - Located in the neck, just below the larynx - Two lobes of endocrine tissue joined in middle by narrow strip of gland (isthmus) - Consists of **two** distinct secretory cell types a. **Follicular cells** - Secrete **two** iodine-containing hormones 1. **Tetra-iodothyronine (T4 or thyroxine)** 2. **Tri-iodothyronine (T3)** biologically active form of T4 b. **Parafollicular** 'para' = alongside **or C cells** - Secrete calcitonin (peptide hormone) A close-up of a microscope Description automatically generated **Thyroid Hormone -- Synthesis, Storage & Release** - **Formed from iodide (I-) & tyrosine** amino acid - Synthesis of tyrosine-containing thyroglobulin (TG or TGB) in follicular cells & export into colloid - Active uptake of iodide (I-) by follicular cells, oxidation into 'active' iodide & diffusion into colloid - Attachment of iodide to tyrosine residues in TG **⇒ MIT & DIT** - Coupling of a. **MIT & DIT** **⇒ Tri-iodothyronine (T3)** b. **DIT & DIT** **⇒ Tetra-iodothyronine (T4)** - T3 & T4 are attached to TG & stored in colloid until release - **Release stimulated by TSH** - Endocytosis of synthesised TG-containing colloid by follicular cells - Proteolytic digestion of TG to release a. **T3 & T4** b. **MIT & DIT** ⇒ Secretion / diffusion of T3 & T4 into blood / Transportation in carrier (TBG)-bound form in the bloodstream as T3 and T4 are lipophilic/hydrophobic ⇒ T4 converted to active T3 in the liver & kidneys ⇒ Iodide removed from MIT & DIT and recycled A diagram of a cell Description automatically generated **Functions of Thyroid Hormone** T3 (active form) - **Effect on Normal Growth & CNS Development** - Effects on normal growth mediated via GH & IGF-1 a. Stimulates GH secretion by anterior pituitary & hepatic production of IGF-1 b. Promotes GH & IGF-1 effects on protein synthesis & skeletal growth - Required for normal development of the nervous system in infants & children - Promotes normal CNS activity in adults - **Effect on Metabolic Rate & Heat Production** - Increases the overall basal metabolic rate & heat production **'calorigenic effect'** a. **Main regulator of resting O2 consumption & energy expenditure** - **Effect on Intermediary Metabolism** - Biphasic effects on carbohydrate, fat and protein metabolism - **Effect on Sympathetic Activity** in nervous system - Increases cellular responsiveness to catecholamines via β-receptor located on the heart cell up-regulation more activity of noradrenaline and adrenaline ⇒ ↑ **myocardial contractility & HR** **TH -- Control of Release & Function**  **Control of Thyroid Secretion** A diagram of a structure Description automatically generated **The Adrenal Glands** - 'Adrenal' -- 'next to the kidney' - Paired organs that cap the kidneys sit on top of the kidney - Each consists of **two** distinct secretory organs: - An outer **adrenal cortex**; secretes **three** types of steroid hormones a. **Mineralocorticoids (aldosterone)** b. **Glucocorticoids (cortisol)** c. **Sex hormones (dehydroepiandrosterone, DHEA)** - An inner **adrenal** **medulla** sympathetic neuronal structure; secretes catecholamines -- AD & NA  **The Adrenal Cortex** - Consists of **three** layers or zones: 1. **Zona glomerulosa** - Mineralocorticoids (aldosterone) promotes sodium reabsorption -- fluid retention ↑ - **Regulate Na+ & K+ balance and BP homeostasis** 2. **Zona fasciculata** - Glucocorticoids (cortisol) major stress hormone a. **Long-term control of metabolism** b. **Adaptation to stress** 3. **Zona reticularis** inner most layer - Sex hormones (dehydroepiandrosterone, DHEA) - **Supplement gonadal sex steroids** **The Endocrine System 3** **The Adrenocortical Hormones** - **Mineralocorticoids** **(aldosterone)** - Essential for life - Maintain Na+ & K+ balance and ECF volume blood vol - Principal site of action is the distal & collecting tubules of the kidney a. Promote Na+ retention reabsorption & K+ excretion ⇒ ↑ **fluid retention & expansion of ECF volume** - Actions mediated via intracellular receptors - Secretion regulated by angiotensin II (RAAS), elevated serum K+ levels & ACTH (minor) - **Glucocorticoids** **(cortisol)** - Involved in the regulation of carbohydrate, protein and fat metabolism a. **↑ gluconeogenesis** biosynthesis/production of glucose from certain non-carbohydrate carbon substrates in the liver and **↓ cellular glucose uptake and utilisation** ⇒ **↑ blood glucose levels** b. **↓ protein synthesis** and **↑ protein catabolism in muscle** ⇒ **↑ mobilisation of free amino acids** c. **↑ lipolysis** break-down of triglycerides ⇒ **↑ mobilisation and oxidation of free fatty acids** - Play a key role in adaptation to stress - Exert anti-inflammatory & immunosuppressive effects 2^nd^/3^rd^ year !  A diagram of a human body Description automatically generated **The HPA** hypothalamic-pituitary-adrenal **Feedback System**  responds to stress **The Anti-inflammatory & Immunosuppressive Actions of Cortisol** Diagram of a diagram of a human body Description automatically generated tone-down the immune response **The Adrenocortical Hormones** - **Sex hormones ('androgenic' DHEA)** - Supplement sex hormones secreted by gonads - Exert minor effects on reproductive function - Physiologically significant in females a. **Growth of pubic and axillary hair** b. **Enhancement of pubertal growth spurt** c. **Development and maintenance of female sex drive** - Promote protein anabolism and growth **The Adrenal Medulla** inner part of adrenal gland - A modified sympathetic postganglionic neuron - Innervated by preganglionic sympathetic axons - Secretes stimulated by ACh ? -- **Adrenaline & Noradrenaline (& Dopamine)** - **Main functions:** - Reinforce **"fight-or-flight"** responses a. **Maintenance of arterial blood pressure** b. **↑ heart rate, cardiac output & respiratory rate** c. **↑ glycogenolysis ⇒ ↑ glucose mobilisation** d. **↑ lipolysis ⇒ ↑ mobilisation of free fatty acids** **The Endocrine Pancreas** - Consists of clusters or 'islands' of secretory cells, called islets of Langerhans - Comprise **three** types of secretory cells 1. **α** (alpha) cells -- secrete **glucagon** 2. **β** (beta) cells -- secrete **insulin** 3. **δ** (delta) cells -- secrete **somatostatin** - Secretions regulated by changes in blood glucose concentration - **The Pancreas and Secretory Cells** endocrine portion of pancreas release hormones into the bloodstream ! **Pancreas Hormones** - **Insulin** - Important anabolic hormone -- **regulates fuel metabolism** - Promotes cellular **uptake** & **storage** of glucose, fatty acids and amino acids ⇒ **↓ blood levels** - Enhances their conversion into glycogen especially in the liver, triglycerides and amino acids into proteins a. **↑ glycogenesis** conversion of glucose to glycogen**, ↓ glycogenolysis & gluconeogenesis** production of glucose from non-carbohydrates b. **↑ triglyceride synthesis** and **↓ lipolysis** break-down of fat into free fatty acids c. **↑ protein synthesis** and **↓ protein degradation** - Effects mediated via insulin receptors (TK-linked) - **Insulin -- Control of Release & Actions** 1\) increase in blood glucose (eat large meal) 2\) activate Islet beta cells 3\) increase insulin secretion \- Once digestive system becomes busy, we need insulin to **control/reduce** the level of glucose in the BS \- **Incretins**; use to treat obesity -- e.g. monzaro -- lose appetite/effective option - **Glucagon** - Generally opposes actions of insulin - Mobilises energy-rich molecules from storage sites into blood stream ⇒ **↑ blood levels** a. **↓ glycogenesis, ↑ glycogenolysis & gluconeogenesis** ⇒ **↑ hepatic glucose production & release** b. **↑ lipolysis & ketogenesis** produce ketone (alternative energy source)**, ↓ triglyceride synthesis** c. **↓ protein synthesis** and **↑ protein degradation** - Secreted in response to a direct effect of a fall in blood glucose concentration - **Complementary Interactions of Glucagon and Insulin** A diagram of blood glucose Description automatically generated **Hormones Involved in Calcium Homeostasis** important role in bone formation - **Parathyroid hormone (PTH)** - Secreted by parathyroid glands (4 rice grain-sized glands located on dorsal back surface of thyroid glands) - Single most important regulator of blood Ca2+ levels (\[Ca2+\]) - Raises plasma Ca2+ levels via **three** different mechanisms: 1. **↑ bone resorption** ⇒ **↑ release of Ca2+** and other minerals **into blood** 2. **↑ renal reabsorption of Ca2+** ⇒ **↑ blood \[Ca2+\]** 3. **↑ renal activation of Vitamin D** in the kidney ⇒ **↑ intestinal absorption of Ca2+** ⇒ **↑ blood \[Ca2+\]** - Secretion regulated by blood Ca2+ levels decreased calcium stimulate PT to release more PTH - **Regulation of Plasma \[Ca2+\] by PTH**  Diagram of a human body Description automatically generated **Hormones Involved in Calcium Homeostasis** - **Vitamin D (cholecalciferol)** - Synthesized by the skin through exposure to light & activated in the liver and kidneys - Supplemented by dietary intake vitamin D - Second most important regulator of blood \[Ca2+\] - Controls plasma Ca2+ levels via three mechanisms: 1. **↑ intestinal absorption of Ca2+** ⇒ ↑ **blood \[Ca2+\]** 2. **↑ bone resorption** ⇒ ↑ **release of Ca2+ into blood** 3. **↓ PTH synthesis** negative feedback control **Activation & Actions of Vitamin D**  Vitamin D3/25-OH-Vitamin D2 -- biologically inactive **Actions & Interactions of PTH & Vitamin D** **\ Hormones Involved in Calcium Homeostasis** - **Calcitonin** - Secreted by parafollicular or C cells of thyroid gland peptide hormone - Exerts **opposite** effects to PTH - Lowers plasma Ca2+ levels via two mechanisms: 1. **↓ bone resorption** ⇒ **↓ release of Ca2+ into blood** 2. **↓ renal reabsorption of Ca2+** ⇒ **↓ blood \[Ca2+\]** - *Minor* physiological regulator of blood \[Ca2+\] - Secretion regulated by blood Ca2+ levels - **Control of PTH & Calcitonin Secretion**  **The Gonads** - The gonads are the sex organs, comprising the - **Testes** -- the male sex organ - **Ovaries** -- the female sex organ - The primary functions of the **testes** include; - Production of sperm (spermatogenesis) - Secretion of male sex hormones (androgens) -- **testosterone** - The primary functions of the **ovaries** include; - Production of ova or egg cells (oogenesis) - Secretion of female sex hormones -- **oestrogens & progestins/progestogens (progesterone)** **The Male Sex Hormones (Androgens)** - **Testosterone** - Secreted by Leydig cells of the testes - Due to testosterone's low biological activity Converted into dihydrotestosterone (DHT) in target tissues - Production increases rapidly at puberty - Key functions: a. **Promotes development of the male reproductive organs** b. **Promotes development & maintenance of male secondary sexual characteristics** -- facial hair, deeper voice, etc c. **Increases & maintains sexual drive and desire** d. **Increases bone thickness and periosteal bone formation** e. **Increases basal metabolic rate and muscle mass** f. **Promotes RBC formation & protects against anaemia** - **Regulation of Testosterone Production** **The Female Sex Hormones** - **Oestrogens (oestradiol)** - Secreted by granulosa cells of the ovarian follicle - Production increases rapidly at puberty - Key functions: a. **Promotes maturation & maintenance of the reproductive organs in their mature functional state** b. **Promotes development & maintenance of female secondary sexual characteristics** -- breast, pubic hair, fat distribution c. **Plays critical roles, along with progesterone, in the normal female reproductive cycle (menstruation, pregnancy and childbirth)** d. **Reduces bone resorption & increases bone density** important ! e. **Mediates important cardio- and vaso-protective effects** - lower risk of cardiovascular diseases - **Progestins/Progestogens (Progesterone)** - Secreted by granulosa & theca cells of the ovarian follicle - Production increases markedly during the luteal phase - Called the "hormone of pregnancy" - Key functions: a. **Plays critical roles, along with oestradiol, in the normal female reproductive cycle** - Helps mediate sexual response in the brain - Prepares the uterus for implantation - Renders cervical canal impenetrable to sperm after implantation - Inhibits uterine contractions during gestation b. **Inhibits Na+ retaining activity of aldosterone ⇒ ↑ natriuresis ⇒ ↓ fluid retention** **Mean Sex Hormone Levels in Plasma in Males and Females**  as oestrogens ↓, risk of cardio-diseases ↑