MPharm Programme: Normal Systems - The Endocrine System 1-3 PDF

WEEK 15 MPharm Programme Normal Systems The Endocrine System 1 Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA112 The Endocrine System WEEK Outline of Lecture 15 General principles of endocrine function Types of hormones & signalling pathways or mech...

WEEK 15 MPharm Programme Normal Systems The Endocrine System 1 Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA112 The Endocrine System WEEK Outline of Lecture 15 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 Slide 2 of 85 MPharm PHA112 The Endocrine System Learning Outcomes WEEK 15 At the end of this lecture, you should be able to: 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 undersecretion of the major hormones Slide 3 of 85 MPharm PHA112 The Endocrine System WEEK 15 General Principles of Endocrine Function Slide 4 of 85 MPharm PHA112 The Endocrine System The Endocrine System WEEK 15 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 Slide 5 of 85 MPharm PHA112 The Endocrine System WEEK 15 Slide 6 of 85 The Endocrine System MPharm PHA112 The Endocrine System WEEK 15 Slide 7 of 85 The Endocrine System MPharm PHA112 The Endocrine System WEEK 15 Functions of the Endocrine System One of the body’s two major regulatory systems 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 Slide 8 of 85 MPharm PHA112 The Endocrine System WEEK The Endocrine System 15 Chemical Classification of Hormones Amines & Amino Acid derivatives NA, AD, DA, melatonin, T3 & T4 Polypeptides, Proteins & Glycoproteins TRH, ADH, GH, FSH, insulin Steroids – derived from cholesterol Cortisol, testosterone, estradiol, progesterone Hydrophilic vs Lipophilic hormones Slide 9 of 85 MPharm PHA112 The Endocrine System WEEK 15 Synthesis & Transport of Hormones Synthesis Vesicle-mediated pathway Synthesised in rER & packaged in secretory vesicles polypeptide / protein hormones Non-vesicle-mediated pathway Synthesised in sER & directly released steroid hormones Transport Free & unbound – peptide hormones & amines Carrier protein-bound – steroid & thyroid hormones Slide 10 of 85 MPharm PHA112 The Endocrine System WEEK 15 Synthesis & Transport of Hormones Slide 11 of 85 MPharm PHA112 The Endocrine System WEEK 15 Control of Hormonal Secretion Timing/Pattern of secretion Pulsatile or cyclical Diurnal or circadian rhythm Negative-feedback control End-product inhibition Slide 12 of 85 MPharm PHA112 The Endocrine System WEEK Hormonal Signalling 15 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: Cell surface receptors Receptor-ion channels G-protein coupled receptors Tyrosine kinase-linked receptors Intracellular or nuclear receptors Slide 13 of 85 MPharm PHA112 The Endocrine System Endocrine Disorders WEEK 15 May result from: Hyposecretion Endocrine gland secretes too little of its hormone Primary, Secondary or Tertiary Hypersecretion Endocrine gland secretes too much of its hormone Primary, Secondary or Tertiary Abnormal Target Cell Responsiveness Receptor down-regulation Receptor up-regulation Slide 14 of 85 MPharm PHA112 The Endocrine System The Endocrine System WEEK 15 Two broad anatomical divisions The Central Endocrine Glands Hypothalamus Pituitary Gland Pineal Gland The Peripheral Endocrine Glands Thyroid glands Adrenal glands Endocrine pancreas Parathyroid glands The Gonads (ovaries & testes) Slide 15 of 85 MPharm PHA112 The Endocrine System WEEK 15 The Central Endocrine Glands Slide 16 of 85 MPharm PHA112 The Endocrine System WEEK 15 The Hypothalamus & Pituitary Gland Both located in the diencephalon 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) Slide 17 of 85 MPharm PHA112 The Endocrine System WEEK 15 The Hypothalamus & Pituitary Gland Slide 18 of 85 MPharm PHA112 The Endocrine System WEEK 15 The Hypothalamus & Pituitary Gland Slide 19 of 85 MPharm PHA112 The Endocrine System WEEK The Hypothalamus 15 18 Brain’s coordinating centre for endocrine, behavioural & autonomic nervous system function Acts as neuroendocrine transducer or bridge receives & integrates multiple brain signals converts the electrical signals into chemical messages releases chemical messengers (hormones) to control secretion of pituitary hormones pituitary hormones control the of peripheral MPharm MPH116 Normal Systems - Theactivity Endocrine System endocrine glands Slide 20 of 85 MPharm PHA112 The Endocrine System WEEK Hypothalamic Hormones 15 Hormones That Regulate Anterior Pituitary Secretions Stimulatory Growth hormone-releasing hormone (GHRH) Thyrotropin-releasing hormone (TRH) Corticotropin-releasing hormone (CRH) Gonadotropin-releasing hormone (GnRH) Inhibitory Somatostatin (Growth hormone-inhibiting hormone; GHIH) Dopamine (Prolactin-inhibiting hormone; PIH) Slide 21 of 85 MPharm PHA112 The Endocrine System WEEK 15 Hypothalamic Releasing Hormones Hypothalamus makes releasing hormones They are sent to the anterior pituitary The anterior pituitary releases its stored tropic hormones into the systemic circulation They tell other endocrine organs in the body to grow & secrete their hormones Slide 22 of 85 MPharm PHA112 The Endocrine System WEEK 15 The Major Hypothalamic Hormones Slide 23 of 85 MPharm PHA112 The Endocrine System WEEK Hypothalamic Hormones 15 Hormones That Are Transported & Stored in The Posterior Pituitary Vasopressin or Antidiuretic hormone (ADH) Oxytocin Slide 24 of 85 MPharm PHA112 The Endocrine System WEEK The Pituitary Gland 15 Hypophysis – located in diencephalon The ‘Master Gland’ – secretes hormones that control the function of many target glands & cells Consists of two anatomically & functionally distinct lobes Anterior pituitary (Adenohypophysis) Secretes & releases 6 major hormones Posterior pituitary (Neurohypophysis) Stores & releases 2 hormones Slide 25 of 85 MPharm PHA112 The Endocrine System WEEK 15 Slide 26 of 85 The Pituitary Gland MPharm PHA112 The Endocrine System WEEK 15 Slide 27 of 85 The Pituitary Gland MPharm PHA112 The Endocrine System WEEK 15 Anterior Pituitary Hormones Growth hormone (GH, somatotropin) Primary hormone for regulation of overall body growth Stimulates growth of soft tissues & bone Stimulates cell division & protein synthesis  tissue hyperplasia & hypertrophy Promotes cartilage & bone growth (in length & thickness) Growth-promoting effects are mediated via stimulated release of insulin-like growth factors (IGFs) or somatomedins by the liver Slide 28 of 85 MPharm PHA112 The Endocrine System WEEK 15 Anterior Pituitary Hormones Growth hormone (cont’d) Important role in intermediary metabolism Exerts largely anti-insulin effects Increases lipolysis   free fatty acid (FFA) mobilization & use as fuel Inhibits peripheral cellular glucose uptake   blood glucose levels and  use of glucose as fuel Secretion modulated by GHRH & somatostatin from hypothalamus Ghrelin from gastric fundus Slide 29 of 85 MPharm PHA112 The Endocrine System WEEK 15 Functions of Growth Hormone Slide 30 of 85 MPharm PHA112 The Endocrine System WEEK 15 Slide 31 of 85 GH – Control of Release & Functions MPharm PHA112 The Endocrine System WEEK 16 MPharm Programme Normal Systems The Endocrine System 2 Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA112 The Endocrine System WEEK 16 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 Slide 33 of 85 MPharm PHA112 The Endocrine System WEEK 16 Anterior Pituitary Hormones 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 Slide 34 of 85 MPharm PHA112 The Endocrine System WEEK 16 Anterior Pituitary Hormones 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 from hypothalamus Slide 35 of 85 MPharm PHA112 The Endocrine System WEEK 16 Anterior Pituitary Hormones Slide 36 of 85 MPharm PHA112 The Endocrine System WEEK 16 Slide 37 of 85 MPharm PHA112 The Endocrine System WEEK 16 Posterior Pituitary Hormones Slide 38 of 85 MPharm PHA112 The Endocrine System WEEK Posterior Pituitary Hormones 16 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 Slide 39 of 85 MPharm PHA112 The Endocrine System WEEK 16 Slide 40 of 85 Posterior Pituitary Hormones MPharm PHA112 The Endocrine System WEEK The Pineal Gland 16 Tiny, pine cone-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-hr ‘day-night’ or ‘light-dark’ cycle Promotes sleep Influences reproductive activity – onset of puberty Slide 41 of 85 MPharm PHA112 The Endocrine System WEEK 16 Pineal Gland & Melatonin Secretion Slide 42 of 85 MPharm PHA112 The Endocrine System WEEK 16 The Peripheral Endocrine Glands Slide 43 of 85 MPharm PHA112 The Endocrine System The Thyroid Gland WEEK 16 Located in the neck, just below the larynx Two lobes of endocrine tissue joined in middle by narrow strip of gland (isthmus) Consists of 2 distinct secretory cell types Follicular cells Secrete two iodine-containing hormones Tetra-iodothyronine (T4 or thyroxine) Tri-iodothyronine (T3) Parafollicular or C cells Secrete calcitonin (peptide hormone) Slide 44 of 85 MPharm PHA112 The Endocrine System WEEK 16 Slide 45 of 85 The Thyroid Gland MPharm PHA112 The Endocrine System Thyroid Hormone WEEK 16 Synthesis, Storage & Release Formed from iodide (I-) & tyrosine Synthesis of tyrosine-containing thyroglobulin (TG) in follicular cells & export into colloid Active uptake of iodide (I-) by follicular cells, oxidation (to ‘active’ iodide) & diffusion into colloid Attachment of iodide to tyrosine residues in TG  MIT & DIT Coupling of MIT & DIT  Tri-iodothyronine (T3) DIT & DIT  Tetra-iodothyronine (T4) T3 & T4 are attached to TG & stored in colloid until release Slide 46 of 85 MPharm PHA112 The Endocrine System Thyroid Hormone WEEK 16 Synthesis, Storage & Release Release stimulated by TSH Endocytosis of synthesised TG-containing colloid by follicular cells Proteolytic digestion of TG to release T3 & T4 MIT & DIT Secretion / diffusion of T3 & T4 into blood & transportation in carrier (TBG)-bound form T4 converted to active T3 in the liver & kidneys Iodide removed from MIT & DIT and recycled Slide 47 of 85 MPharm PHA112 The Endocrine System WEEK 16 Thyroid Hormone Synthesis, Storage & Release Slide 48 of 85 MPharm PHA112 The Endocrine System WEEK 16 Thyroid Hormone Synthesis, Storage & Release Slide 49 of 85 MPharm PHA112 The Endocrine System WEEK 16 Functions of Thyroid Hormone Effect on Normal Growth & CNS Development Effects on normal growth mediated via GH & IGF-1 Stimulates GH secretion & hepatic production of IGF-1 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 Slide 50 of 85 MPharm PHA112 The Endocrine System WEEK Functions of Thyroid Hormone 16 Effect on Metabolic Rate & Heat Production Increases the overall basal metabolic rate & heat production (‘calorigenic effect’) main regulator of resting O2 consumption & energy expenditure Effect on Intermediary Metabolism Biphasic effects on carbohydrate, fat & protein metabolism Effect on Sympathetic Activity Increases cellular responsiveness to catecholamines via receptor up-regulation   myocardial contractility & HR Slide 51 of 85 MPharm PHA112 The Endocrine System WEEK 16 TH – Control of Release & Functions Slide 52 of 85 MPharm PHA112 The Endocrine System WEEK 16 Control of Thyroid Secretion Slide 53 of 85 MPharm PHA112 The Endocrine System WEEK The Adrenal Glands 16 ‘Adrenal’ – ‘next to the kidney’ Paired organs that cap the kidneys Each consists of 2 distinct secretory organs: an outer adrenal cortex Secretes 3 types of steroid hormones Mineralocorticoids (aldosterone) Glucocorticoids (cortisol) Sex hormones (Dehydroepiandrosterone, DHEA) an inner adrenal medulla Secretes catecholamines – AD & NA Slide 54 of 85 MPharm PHA112 The Endocrine System WEEK 16 Slide 55 of 85 The Adrenal Glands MPharm PHA112 The Endocrine System The Adrenal Cortex WEEK 16 Consists of three layers or zones: Zona glomerulosa Mineralocorticoids (aldosterone) Regulate Na+ & K+ balance & BP homeostasis Zona fasciculata Glucocorticoids (cortisol) Long-term control of metabolism Adaptation to stress Zona reticularis Sex hormones (Dehydroepiandrosterone, DHEA) Supplement gonadal sex steroids Slide 56 of 85 MPharm PHA112 The Endocrine System WEEK 16 MPharm Programme Normal Systems The Endocrine System 3 Dr G Boachie-Ansah [email protected] Dale 113 ext. 2617 MPharm PHA112 The Endocrine System WEEK 16 The Adrenocortical Hormones Mineralocorticoids (aldosterone) essential for life maintain Na+ & K+ balance and ECF volume principal site of action is the distal & collecting tubules of the kidney promote Na+ retention & 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) Slide 58 of 85 MPharm PHA112 The Endocrine System WEEK 16 Control of Aldosterone Release Slide 59 of 85 MPharm PHA112 The Endocrine System WEEK 16 The Adrenocortical Hormones Glucocorticoids (cortisol) involved in the regulation of carbohydrate, protein & fat metabolism  gluconeogenesis and  cellular glucose uptake and utilisation   blood glucose levels  protein synthesis and  protein catabolism in muscle   mobilisation of free amino acids  lipolysis   mobilisation & oxidation of free fatty acids play a key role in adaptation to stress exert anti-inflammatory & immunosuppressive effects Slide 60 of 85 MPharm PHA112 The Endocrine System WEEK 16 Cortisol – Control of Release & Actions Slide 61 of 85 MPharm PHA112 The Endocrine System WEEK 16 Slide 62 of 85 The HPA Feedback System MPharm PHA112 The Endocrine System WEEK 16 The Anti-inflammatory & Immunosuppressive Actions of Cortisol Slide 63 of 85 MPharm PHA112 The Endocrine System WEEK 16 The Adrenocortical Hormones Sex hormones (‘androgenic’ DHEA) supplement sex hormones secreted by gonads exert minor effects on reproductive function physiologically significant in females Growth of pubic & axillary hair Enhancement of pubertal growth spurt Development & maintenance of female sex drive promote protein anabolism & growth Slide 64 of 85 MPharm PHA112 The Endocrine System WEEK The Adrenal Medulla 16 A modified sympathetic postganglionic neuron Innervated by preganglionic sympathetic axons Secretes Adrenaline & Noradrenaline (& dopamine) Main functions Reinforce “fight-or-flight” responses Maintenance of arterial blood pressure  heart rate, cardiac output & respiratory rate  glycogenolysis   glucose mobilisation  lipolysis   mobilisation of free fatty acids Slide 65 of 85 MPharm PHA112 The Endocrine System WEEK The Endocrine Pancreas 16 Consists of clusters or ‘islands’ of secretory cells, called islets of Langerhans Comprise 3 types of secretory cells  (alpha) cells Secrete glucagon  (beta) cells Secrete insulin D (delta) cells Secrete somatostatin Secretions regulated by changes in blood glucose concentration Slide 66 of 85 MPharm PHA112 The Endocrine System WEEK 16 The Pancreas & Secretory Cells Slide 67 of 85 MPharm PHA112 The Endocrine System Pancreas Hormones WEEK 16 Insulin Important anabolic hormone – regulates fuel metabolism Promotes cellular uptake & storage of glucose, fatty acids & amino acids   blood levels Enhances their conversion into glycogen, triglycerides & proteins  glycogenesis,  glycogenolysis & gluconeogenesis  triglyceride synthesis and  lipolysis  protein synthesis and  protein degradation Effects mediated via insulin receptors (TK-linked) Slide 68 of 85 MPharm PHA112 The Endocrine System WEEK 16 Slide 69 of 85 Main Actions of Insulin MPharm PHA112 The Endocrine System WEEK 16 Insulin – Control of Release & Actions Slide 70 of 85 MPharm PHA112 The Endocrine System WEEK Pancreas Hormones 16 Glucagon Generally opposes actions of insulin Mobilizes energy-rich molecules from storage sites into blood stream   blood levels  glycogenesis,  glycogenolysis & gluconeogenesis   hepatic glucose production & release  lipolysis & ketogenesis,  triglyceride synthesis  protein synthesis and  protein degradation Secreted in response to a direct effect of a fall in blood glucose concentration Slide 71 of 85 MPharm PHA112 The Endocrine System WEEK 16 Complementary Interactions of Glucagon and insulin Slide 72 of 85 MPharm PHA112 The Endocrine System WEEK 16 Hormones Involved in Calcium Homeostasis Parathyroid hormone (PTH) Secreted by parathyroid glands (4 rice grain-sized glands located on dorsal surface of thyroid glands) Single most important regulator of blood Ca++ levels ([Ca++]) Raises plasma Ca++ levels via 3 mechanisms:  bone resorption   release of Ca++ into blood  renal reabsorption of Ca++   blood [Ca++]  renal activation of vitamin D   intestinal absorption of Ca++   blood [Ca++] Secretion regulated by blood Ca++ levels Slide 73 of 85 MPharm PHA112 The Endocrine System WEEK 16 Regulation of Plasma [Ca++] by PTH Slide 74 of 85 MPharm PHA112 The Endocrine System Hormones Involved in Calcium Homeostasis WEEK 16 Vitamin D (cholecalciferol) Synthesized by the skin & activated in the liver & kidneys Supplemented by dietary intake Second most important regulator of blood [Ca++] Controls plasma Ca++ levels via 3 mechanisms:  intestinal absorption of Ca++   blood [Ca++]  bone resorption   release of Ca++ into blood  PTH synthesis Slide 75 of 85 MPharm PHA112 The Endocrine System WEEK 16 Activation & Actions of Vitamin D Slide 76 of 85 MPharm PHA112 The Endocrine System WEEK 16 Actions & Interactions of PTH & Vit D Slide 77 of 85 MPharm PHA112 The Endocrine System WEEK 16 Hormones Involved in Calcium Homeostasis Calcitonin Secreted by parafollicular or C cells of thyroid gland Exerts opposite effects to PTH Lowers plasma Ca++ levels via 2 mechanisms:  bone resorption   release of Ca++ into blood  renal reabsorption of Ca++   blood [Ca++] Minor physiological regulator of blood [Ca++] Secretion regulated by blood Ca++ levels Slide 78 of 85 MPharm PHA112 The Endocrine System WEEK 16 Control of PTH & calcitonin secretion Slide 79 of 85 MPharm PHA112 The Endocrine System WEEK The Gonads 16 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) Slide 80 of 85 MPharm PHA112 The Endocrine System WEEK 16 The Male Sex Hormones (Androgens) Testosterone Secreted by Leydig cells of the testes Converted into dihydrotestosterone (DHT) in target tissues Production increases rapidly at puberty Key functions: Promotes development of the male reproductive organs Promotes development & maintenance of male secondary sexual characteristics – facial hair, deeper voice, etc Increases & maintains sexual drive & desire Increases bone thickness & periosteal bone formation Increases basal metabolic rate & muscle mass Promotes RBC formation & protects against anaemia Slide 81 of 85 MPharm PHA112 The Endocrine System WEEK 16 Regulation of Testosterone Production Slide 82 of 85 MPharm PHA112 The Endocrine System WEEK The Female Sex Hormones 16 Oestrogens (Oestradiol) Secreted by granulosa cells of the ovarian follicle Production increases rapidly at puberty Key functions: Promotes maturation & maintenance of the reproductive organs in their mature functional state Promotes development & maintenance of female secondary sexual characteristics – breasts, pubic hair, fat distribution Plays critical roles, along with progesterone, in the normal female reproductive cycle (menstruation, pregnancy & childbirth) Reduces bone resorption & increases bone density Mediates important cardio- and vaso-protective effects Slide 83 of 85 MPharm PHA112 The Endocrine System The Female Sex Hormones WEEK 16 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: 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 Inhibits Na+-retaining activity of aldosterone   natriuresis   fluid retention Slide 84 of 85 MPharm PHA112 The Endocrine System WEEK 16 Mean Sex Hormone Levels in Plasma in Males and Females Slide 85 of 85 MPharm PHA112 The Endocrine System