Week 7 Endocrine System Lecture Notes PDF

Dr Yasser Abdel-Wahab (Module Coordinator) WEEK 7 Introduction to Anatomy and Physiology of the Endocrine System Aims: To give an overview of the Anatomy and Physiology of the Endocrine System Lecture Outlines: 1. The organisation of the endocrine system 2. Overview of the endocrine...

Dr Yasser Abdel-Wahab (Module Coordinator) WEEK 7 Introduction to Anatomy and Physiology of the Endocrine System Aims: To give an overview of the Anatomy and Physiology of the Endocrine System Lecture Outlines: 1. The organisation of the endocrine system 2. Overview of the endocrine system and classification of hormones 3. Hormones biosynthesis, secretion, action and regulation of secretion. 4. Thyroid gland 5. Parathyroid glands 6. The endocrine pancreas 7. Pituitary gland 8. Adrenal glands Intended Learning outcomes are: Give an overview of the anatomy of the endocrine glands Appreciate what hormones are, how they are classified and the three main types of hormone. Outline the regulation of hormone secretion, biosynthesis of hormones, stimulus secretion coupling, and the action of hormones on their target cells. Name the hormones produced by the thyroid gland, and outline the steps involved in synthesis and release of the main thyroid hormones. Describe the regulation of secretion of thyroid hormones, and the cellular and metabolic actions of these hormones. Discuss the importance of calcium in the body Outline the synthesis, secretion and actions of parathyroid hormone (PTH). Appreciate the importance of vitamin D, sources of Vit D and its metabolism. Give an overview of the endocrine portion of the pancreas, including the 4 main endocrine cells and their hormones Understand the counter-regulation (paracrine) of secretion within Islets of Langerhans. Outline the structure and biosythesis of insulin. Outline the actions of insulin and glucagon on carbohydrate, protein and lipid metabolism. Appreciate the actions of somatostatin and pancreatic polypeptide. Describe the neurosecretory system and its importance in linking the hypothalamus to the pituitary gland Describe the secretion, action and regulation of the two hormones released by the posterior pituitary gland. Give an overview of the 7 hormones secreted by the anterior pituitary gland, their functions and regulation of their secretion by inhibiting and releasing factors from the hypothalamus. Name the three types of hormone produced by the adrenal cortex, and describe the functions of the glucocorticoids. Outline the functions of the mineralocorticoid hormone aldosterone. 1  Dr Yasser Abdel-Wahab (Module Coordinator) Anatomy of the endocrine system The body contains two kinds of glands as shown below: Exocrine glands: secrete their products into ducts, and these ducts carry the secretions into body cavities and lumina of various organs. Endocrine glands: secrete their products (hormones) into the extracellular space around the secretory cells, rather than into ducts. These hormone secretions then diffuse into capillaries and are carried to their target cells in the blood. Structure of the endocrine system The endocrine glands of the body constitute the endocrine system (see diagram) and include:  The pituitary gland (hypophysis)  Thyroid and parathyroid glands  Adrenal glands  Pineal gland (Epiphsysis cerebri) In addition, several organs of the body contain endocrine tissues but are not endocrine glands exclusively; they include:  The hypothalamus  Thymus  Pancreas  Ovaries and Testes  Kidneys  Stomach  Liver  Small intestine  Skin  Heart  Placenta 2  Dr Yasser Abdel-Wahab (Module Coordinator) The Pituitary Gland (Hypophysis) The pituitary gland is pea-sized and measures about 1.3 cm in diameter. It lies in the Sella Turcica of the sphenoid bone and is attached to the hypothalamus via a stalk like structure called the infundibulum, as shown in the diagram below. It has two anatomically and functionally separate portions:  The anterior pituitary gland (anterior lobe)  The posterior pituitary gland (posterior lobe) Anterior pituitary gland:  Accounts for about 75% of the total weight of the pituitary gland. The anterior pituitary gland secretes hormones which regulate a wide range of bodily activities from growth to reproduction.  The release of hormones from the anterior pituitary glands is stimulated by releasing hormones and suppressed by inhibiting hormones from the hypothalamus. There are five principal types of anterior pituitary cells, which produce and secrete several hormones as listed below: 1 2 3 4 5 Posterior pituitary gland:  Unlike the anterior region, the posterior pituitary does not synthesize hormones  It does store and release two hormones: o Oxytocin (OT) – which stimulates smooth muscle contraction of uterus or mammary glands in females and prostate gland in males 3  Dr Yasser Abdel-Wahab (Module Coordinator) o Antidiuretic hormone (ADH) – acts on distal convoluted tubules and collecting ducts of the kidney to regulate water reabsorption  It consists of cells called pituicytes These two hormones are synthesized in the supraoptic and paraventricular nuclei of the hypothalamus before being transported along the nerves for storage at the nerve endings and release by the posterior pituitary gland. The anatomy, blood supply and nerve link between the pituitary gland and hypothalamus are shown in the diagram right. Thyroid Gland  Located just below the larynx (voice box) (see diagram right).  It has 2 lobes, a right and left lobe which lie on each side of the trachea.  The lobes are connected by a mass of tissue called the isthmus which lies in front of the trachea. The gland contains microscopic spherical sacs called thyroid follicles which are surrounded by follicular cells. Follicular cells produce two hormones: 1. T4 (thyroxine) 2. T3 (triiodothyronine) Other cells called parafollicular cells produce the hormone: 1. calcitonin Parathyroid glands These are attached to the posterior surface of the thyroid gland as shown in the diagram below. Microscopically the parathyroid glands two types of epithelial cells: The most numerous are the and the other cell type is 4  Dr Yasser Abdel-Wahab (Module Coordinator) Adrenal glands (suprarenal) The adrenal glands lie superior to the kidney and are differentiated into 2 main regions as shown in the diagram below:  Outer adrenal cortex – makes up the main bulk of the gland  Inner adrenal medulla – contains blood vessels Adrenal cortex is subdivided into 3 zones:  Zona glomerulosa (outer zone) – cells in this region secrete hormones called mineralocorticoids  Zona fasciculata (middle zone) – widest of the three zones and the cells in this zone mainly secrete glucocorticoids  Zona reticularis (inner zone) – cells in this zone synthesize and secrete minute amounts of sex hormones called gonadocorticoids. Adrenal medulla – contains two populations of secretory cells which produce and secrete epinephrine (adrenaline) and norepinephrine (noradrenaline) Pineal gland This endocrine gland is attached to the roof of the third ventricle in the brain. It contains secretory cells known as pinealocytes which produce and secrete melatonin. The Pancreas The pancreas is both an exocrine and endocrine gland. The endocrine portion of the pancreas is known as the Islets of Langerhans (Islets), with about 1 million Islets scattered throughout the exocrine tissue of the pancreas. The Islets contain 4 types of cells:  Alpha cells – secrete glucagon  Beta cells – secrete insulin  Delta cells – secrete somatostatin  F cells or PP-cells – secrete pancreatic polypeptide 5  Dr Yasser Abdel-Wahab (Module Coordinator) The Thymus The thymus is located in the mediastinum just under the sternum as shown in the diagram below. Hormones produced by the thymus are: The Ovaries and Testes The endocrine actions of the ovaries and testes are highlighted in the flow diagram below. Physiology of the endocrine system The endocrine glands produce and secrete hormones which are distributed to the target cells by circulation in the blood. These hormones then interact with receptors on the target cells to bring about a biological response. Hormones are essentially chemical messengers, similar to electrical messages being sent by nerves to target cells to elicit a biological response. 6  Dr Yasser Abdel-Wahab (Module Coordinator) The principle endocrine glands of the body are:  Pituitary gland (anterior and posterior)  Thyroid gland and Parathyroid glands  Adrenal glands (cortex and medulla)  Pancreas (Islets of Langerhans)  Testes and Ovaries (and also placenta)  Gastrointestinal tract What is the criteria for classification as a hormone? 1. Cut Out Gland → Abnormality 2. Extract Gland/Reinject → Abnormality 3. Reimplant Gland → Abnormality 4. Synthesise Hormone/Inject → Abnormality This is because the endocrine glands secrete hormones which act on target cells, and without the hormone, normal homeostasis would be disturbed. Nature of hormones There are 3 main types of hormone: 1 and 2 above bind to their specific receptors on the cell membrane of target cells, whereas 3 (steroids) are able to enter the cells by crossing the lipid rich plasma membrane to interact with intracellular receptors. Regulation of hormone secretion Hormones are released when a biological effect is required.  Negative feedback loops act to inhibit hormone secretion  Hormone A can act on the gland to inhibit it own secretion. 7  Dr Yasser Abdel-Wahab (Module Coordinator)  It can stimulate the release of other hormones (B and C) which will counteract its biological effect.  The biological effect will feedback to the gland to reduce secretion of the hormone A. E.g. When blood sugar levels are raised insulin is secreted from Islets of Langerhans in the pancreas. Insulin acts of target cells, such as skeletal muscle cells, to increase glucose uptake into these cells. This reduces the blood sugar level, which in turn causes a decrease in insulin secretion. Hormone biosynthesis is highlighted in the chart below  Steroid hormones like testosterone are synthesized from cholesterol and can diffuse out of the cells across the cell membrane.  Polypeptides and amines are synthesized from amino acids in the cells, and are then packaged in membrane-bound vesicles.  When required, these granules fuse with the cell membrane and release the hormones by exocytosis. Biosynthesis of polypeptide hormones  The polypeptides are genetically coded in the DNA, and transcription of DNA into messengerRNA (mRNA) allows the cell to read the code and synthesize the hormone.  RNA is translated by ribosomes in the rough endoplasmic reticulum (RER) which joins amino acids together to form a chain of amino acids (peptide or polypeptide).  The polypeptides are then transported to the Golgi apparatus for packaging into secretory granules, which are then stored in the cytoplasm of the cell prior to exocytosis. Stimulus-secretion coupling Stimulus-secretion coupling occurs when a stimulus acts on the endocrine cell, but the secretion of the hormone needs the coupling of other factors to aid/finalise exocytosis of the hormone from the cell. 8  Dr Yasser Abdel-Wahab (Module Coordinator) For example, insulin secretion is stimulated by increased blood glucose. The glucose enters the insulin secreting cells, is metabolized and generates ATP. ATP causes closure of KATP channels and leads to membrane depolarization. This in turn opens voltage-dependent calcium channels, allowing calcium to enter the cells. The calcium is essential for the exocytosis of insulin. Thus calcium is the coupling factor. Mechanisms of hormone action Hormones travel to target cells to elicit a biological response. Hormones either:  bind to their specific receptors on the cell membrane (e.g. G-protein-coupled receptors) if they are lipid insoluble (amines and peptide hormones)  or they are absorbed into the cell across the cell membrane and can enter the cell nucleus to bind to intracellular receptor if they are lipid soluble (steroid hormones).  Bind to cell membrane receptors causes release of second messenger within the cytoplasm (such as cyclic AMP) which cause a cascade of other reactions within the cells to elicit the desired response.  Those that bind to nuclear receptors can alter gene expression (mRNA), to increase or decrease levels of specific proteins which will have long-term effects. Thyroid gland physiology The thyroid gland produces and secretes three hormones.  Calcitonin – produced by parafollicular cells is a small peptide/protein hormone, which regulate blood Ca2+ levels.  Triiodothyronine (T3) and Thyroxine are amine derived from the amino acid tyrosine, and they regulate metabolism, growth and development. The thyroid gland usually weighs about 20g and has an extensive blood supply with flow of 4 – 6ml/g/min which is similar to that of the kidneys (3ml/g/min). Nerve supply: The thyroid is innervated by the Autonomic Nervous System (both parasympathetic and sympathetic). 9  Dr Yasser Abdel-Wahab (Module Coordinator) Thyroid glands contains numerous follicles lined with follicular cells (epithelial cells), surrounding a cavity filled with viscous fluid called colloid which contains large amounts of proteins. Follicular cells – synthesize the globular protein thyroglobulin and secrete it into the colloid Thyroglobulin is used for the synthesis of T3 and T4 and contains the amino acid tyrosine Synthesis, storage, release of T3 and T4 There are 6 main steps in the synthesis and release of T3 and T4 1. Uptake of iodide 2. Oxidation of iodide 3. Iodination of tyrosine on thyroglobulin 4. Coupling of iodotyrosines 5. Proteolytic cleavage of thyroglobulin 6. Release of T3 and T4 1. Uptake of iodide Iodide ions are transported from the circulation into the follicular cells by active transport (requires ATP), as iodide concentrations in the follicular cells are high compared to surrounding fluid. 2. Oxidation of iodide Iodide ions (I-) are oxidized by thyroid peroxidase to either iodinium ion I+ or iodide free radical. This occurs near the colloid surface of the follicular cells. 10  Dr Yasser Abdel-Wahab (Module Coordinator) 3. Iodination of tyrosine Thyroid peroxidase also aids the attachment of the iodinium ion to the tyrosine ring of tyrosines within the thyroglobulin. This process is known as iodination. Either one or two iodinium ions will bind to the tyrosine to give either 3- moniodotyrosine (T1) or 3,5-Diiodotyrosine (T2) 4. Coupling of iodotyrosines These iodotyrosine (T1 and T2) are paired by covalent bonds as shown below to give either Thyroxine (T4) or Triiodothryonine (T3) and these thyroid hormones remain attached to the thyroglobulin molecule. There can be 4 – 8 molecules of T3, T4 or both on each thyroglobulin. Steps 2-4 occur in colloid. 5. Proteolytic release of thyroglobulin & 6. Release of T3 and T4 Iodinated thyroglobulin enters the follicular cells from the colloid by pinocytosis (enfolded by plasma membrane to form vesicle which enters cytoplasm). The colloid droplet containing the thyroglobulin fuses with a lysosome. Lysosomal enzymes breakdown the thyroglobulin molecule, releasing the T3 and T4 (plus any T1 and T2). T1 and T2 and their iodides can be recycled. T3 and T4 are lipophilic and can diffuse across the cell membrane out of the follicles and enter the circulation. 11  Dr Yasser Abdel-Wahab (Module Coordinator)  T4 is the main hormone secreted (~90%) with much less T3 being secreted.  T3 is about 4 times more potent than T4 on target tissues.  T3 an T4 are mostly transported in the circulation bound to carrier molecules Regulation of T3 and T4 secretion The synthesis and release of T3 and T4 is controlled by the actions of thyroid-stimulating hormone (TSH) released from the anterior pituitary gland. Stimulus arriving at the hypothalamus to suggest increased need of T3 and T4 causes release of Thyrotropin- releasing hormone (TRH) TRH acts on the anterior pituitary to increase TSH secretion. TSH – binds to TSH receptors in the follicular cells to increases iodide uptake, thyroglobulin synthesis and the increases levels of thyroid peroxidase. T3 and T4 – when circulating levels increase, they give negative feedback to hypothalamus and anterior pituitary to decrease TRH and TSH release. Some circulating T4 is converted to T3 by the liver. In children cold stimulates TRH release which helps them adapt to changes in environmental temperature such as that at birth. Actions of T3 and T4 T3 and T4 have multiple actions in the body as summarised in this flow chart, including increased protein synthesis (eg building or repairing muscle, which requires more energy and more oxygen). They cause and increase in basal metabolic rate: increased oxygen consumption and energy expenditure at rest, which also generate more heat. 12  Dr Yasser Abdel-Wahab (Module Coordinator) Effects of T3 / T4 on carbohydrate, lipid and vitamin metabolism T3 and T4 also alter metabolism: They increase vitamin demand and the conversion of beta carotene to vitamin A. They enhance the lipolytic actions of adrenaline and glucagon to release lipids for energy. They also increase insulin-dependent glucose utilization in target tissue (e.g. skeletal muscle) by help meet increased energy demand, and also glycogen synthesis thus increasing cellular energy reserves. Cellular actions of T3 and T4  T3 and T4 are lipohilic, so they can cross the cell membrane freely.  They bind to receptors in the nucleus of the cells.  This increases DNA-dependent RNA polymerase which increases gene transcription and thus mRNA.  This causes increased protein synthesis of enzymes (e.g. respiratory enzymes).  These proteins then cause the desired long-lasting biological effect. They increase the production of sodium-potassium ATPase which forms part of the pump which expels sodium ions from cells in exchange of potassium ions. This then increases the use of ATP, which burn increases metabolism. The Parathyroid Glands Physiology Roles of Calcium Calcium is important for normal cell function.  It is essential for muscle contraction.  It is main component of bone and teeth  Is essential for normal blood clotting  It triggers exocytosis and stimulates secretion of hormones and other chemical messengers from cells. 13  Dr Yasser Abdel-Wahab (Module Coordinator) Ca2+ homeostasis The plasma levels of Ca2+ are tightly controlled by the actions of parathyroid hormone (PTH), Vitamin D and calcitonin (CT, from parafollicular cells of thyroid gland). They regulate plasma Ca2+ levels by acting on bone, kidneys and the intestines to change absorption, secretion and storage of Ca2+. Calcium in body This flow chart summarizes the distribution of calcium in the body. Regulation of extracellular Ca2+ If plasma and extracellular concentrations of Ca2+ are low:  PTH secretion is stimulated and CT secretion inhibited  PTH increases bone resorption of Ca2+ so that Ca2+ is released from bone into the extracellular fluid and plasma.  PTH increases the reabsorption of Ca2+ from the kidney tubules so less is lost in the urine.  And PTH stimulates the conversion of inactive Vit D3 to active Vit D3 (calcitriol) which then increases intestinal absorption of Ca2+. When plasma calcium levels increase bone resorption is inhibited. Parathyroid/Thyroid Glands The 4 parathyroid glands are embedded in the posterior surface of the thyroid gland (see anatomy above). They contain:  Chief cells – which produce and secrete PTH. 14  Dr Yasser Abdel-Wahab (Module Coordinator)  Oxyphil cell – function unknown.  Stromal fat cells – make up 60-70% of the gland in older people. The Chief cells monitor the plasma concentrations of Ca2+ and secrete PTH when Ca2+ levels are low. Structure of Parathyroid hormone (PTH) PTH is an 84 amino acid polypeptide hormone as shown below. The 34 amino acids of the N-terminal of PTH make up the biologically active part of the hormone. Biosynthesis of PTH Like many other polypeptide hormones, PTH is synthesized as a pre-pro-PTH containing 115 amino acids. The pre-pro hormone is cleaved to a pro-hormone of 90 amino acids and is packaged into secretory granules. Pro-PTH is further cleaved to the active PTH of 84 amino acids, and makes up 93% of the content of the secretory granules. Secretion of PTH Secretion of PTH is dependent on the extracellular Ca2+ concentration. If extracellular/plasma Ca2+ is low then secretion of PTH increases and vice versa. 15  Dr Yasser Abdel-Wahab (Module Coordinator) Actions of PTH The actions of PTH are predominantly to increase the levels of extracellular and plasma Ca2+. PTH acts on three main organs to elicit this effect. 1. Actions of PTH on bone to increase bone resorption  Bone tissue acts as a store of Ca2+  Requires active Vit D3  PTH increases the activity and formation of osteoclasts which increase Ca2+ release from bone tissue.  PTH also decreases the activity and number of osteoblast, thereby decreasing bone formation and the rate of Ca2+ incorporation into bone. 2. Actions of PTH on kidney to increase Ca2+ retention  PTH increases the reabsorption of Ca2+ from the ascending limb of the loop of Henle and the distal tubules of nephrons in the kidney.  Thus the amount of Ca2+ excreted in urine decreases.  The reabsorbed Ca2+ enters the blood capillaries surrounding the kidney tubules and raises plasma Ca2+. PTH also increase the activity of enzymes in the kidney which convert Vitamin D3 to calcitriol (1,25(OH)2D3. Calcitriol also stimulates Ca2+ reabsorption in the kidneys. 3. Actions of PTH on intestine to increase Ca2+ absorption  PTH activates enzymes (1-hydroxylase) in the kidney which increase the formation of calcitriol  Plasma calcitriol levels increase and stimulates the increased absorption of Ca2+ from the intestines.  PTH also causes small increase in intestinal absorption, but the main effect is due to the actions of increased calcitriol. 16  Dr Yasser Abdel-Wahab (Module Coordinator) Vitamin D and the metabolism of vitamin D The two major sources of Vitamin D (cholecalciferol) include:  dietary intake and  conversion of 7-dehydrocholesterol in the skin to vitamin D by UV light. Cholecalciferol is largely inactive and is metabolized in the liver to 25-hydroxy- cholecalciferol. 25-hydroxy-cholecalciferol: is the main form of vitamin D3 in the circulation and is stored in the liver. It can be excreted in bile and reabsorbed from the small intestine. The active metabolic form of vitamin D is 1,25-dihydroxy-cholecacliferol (Calcitriol) The levels of calcitriol are increased when PTH increases expression of the enzyme 1- hydroxylase in the kidney tubules, which convert 25(OH)D3 to 1,25(OH)D3. Another enzyme (24-hydroxylase) found in the kidney tubules also converts 25(OH)D3 to another inactive form (24,25(OH)D3). The source and metabolism is summarized in the flow diagrams below. DIET SKIN The hormone calcitonin (released from parafollicular cells of the thyroid gland) has the opposite effects to PTH, and is released only when plasma Ca2+ is high. The Endocrine Pancreas Physiology The pancreas has both an exocrine portion (see digestive system lecture) and also contains endocrine units known as Islets of Langerhans. 17  Dr Yasser Abdel-Wahab (Module Coordinator) The endocrine cells of the pancreas release hormones which determine the fate of nutrients and regulate nutrient homestasis. The pancreatic endocrine hormones are:  Insulin from B-cells  Glucagon from A-cells  Somatostatin from D-cells  Pancreatic polypeptide from PP- cells (also known as F-cells) Glucose is the main nutrient whose plasma concentrations and fate is regulated by the endocrine pancreatic hormones. When plasma glucose levels are increased (i.e. after a meal)  insulin secretion increases and  glucagon secretion decreases Insulin – stimulates tissues to take up, and use or store glucose, thereby lowering plasma glucose levels Glucagon – stimulates glycogen breakdown in liver and release of glucose from liver into blood. Thus the decrease in glucagon, decrease glucose input into the blood. This allow restoration of normal plasma glucose levels (~3-6 mM). If glucose levels are low then insulin secretion is reduced and glucagon secretion increased. Islets of Langerhans The Islets of Langerhans are small roughly circular clusters of about 3000 – 5000 hormone secreting cells. There are approx 1 million Islets scattered throughout the exocrine tissue of the adult pancreas. 18  Dr Yasser Abdel-Wahab (Module Coordinator) They have a good blood supply and are innervated by the autonomic nervous system (both sympathetic and parasympathetic). The B-cells (secrete insulin) make up the core of the islet and account for approx 75% of the total cell number. The A-cells (secrete glucagon) are the next most abundant cell (~20%) and are found in the islet periphery. The D-cells (secrete somatostatin) account for approx 5% of the cell number in the islet and are also found in the islet periphery. PP-cells are much less abundant but are also found in the periphery. Paracrine effects of islet hormones The islet hormones also regulate the secretion of hormones from the other islet cells as highlighted in this diagram.  Insulin inhibits A-cell glucagon secretion and D-cell somatostatin secretion.  Glucagon stimulates B-cell insulin secretion and D-cell somatostatin secretion.  Somatostatin inhibits B-cell insulin secretion and A-cell glucagon secretion. Insulin Insulin is a 51 amino acid peptide hormones with a molecular weight of 5800 Daltons. It consists of an A-chain (21 amino acids) and a B- chain (30 amino acids). The A and B chains are joined by two disulfide bridges between the amino acid cysteine as shown. Insulin acts to lower blood glucose. Insulin biosynthesis Insulin is synthesized by translation of mRNA on ribosomes of the rough endoplasmic reticulum of B-cells as a single chain of 109 amino acids known as preproinsulin Preproinsulin is cleaved to proinsulin which contains 86 amino acids 19  Dr Yasser Abdel-Wahab (Module Coordinator) Proinsulin is packaged into secretory granules by the Golgi apparatus. Proinsulin is then cleaved by endopeptidases into insulin and c-peptide. C-peptide is released with insulin and exist in equimolar concentrations to insulin in the blood. The diagram to the right shows the structure of preproinsulin. Glucagon Glucagon is a 29 amino acid single chain peptide hormone with a molecular weight of 3485 Daltons. Glucagon acts to increase blood glucose Actions of insulin and glucagon on Carbohydrate metabolism The table/diagram below summarizes the actions of insulin and glucagon on carbohydrate metabolism. FACTOR AFFECTED 20  Dr Yasser Abdel-Wahab (Module Coordinator) Actions of insulin and glucagon on Protein metabolism The table/diagram below summarizes the actions of insulin and glucagon on protein metabolism. FACTOR AFFECTED Actions of insulin and glucagon on Lipid metabolism The table/diagram below summarizes the actions of insulin and glucagon on lipid metabolism. FACTOR AFFECTED Somatostatin Somatostatin is a 14 amino acid cyclic tetradecapeptide. Somatostatin is not only produced and secreted in islets but also in the gastrointestinal tract and the brain. 21  Dr Yasser Abdel-Wahab (Module Coordinator) Actions of somatostatin The main actions of somatostatin are Other hormones inhibited include: From GIT: Gastrin, secretin, motilin, VIP, GIP, CCK, enteroglucagon From thyroid/parathyroid: PTH and calcitonin From Pituitary: Growth hormone (GH) and TSH Other actions of somatostatin include:  Slows rate of gastric empyting,  reduces intestinal smooth muscle contraction,  decreases intestinal blood flow,  reduces pancreatic exocrine secretions Pancreatic polypeptide Pancreatic polypeptide is a 36 amino acid single chain peptide hormone with a molecular weight of approx 4200 Daltons, secreted by the PP cells. Its secretion is increased following exercise, fasting, acute hypoglycaemia and also following a protein rich meal. Actions of pancreatic polypeptide include: The pituitary Gland Physiology There are 9 hormones synthesized and released by the pituitary gland. The pituitary gland has excellent blood supply allowing cells to release their hormones into the circulation. 22  Dr Yasser Abdel-Wahab (Module Coordinator)  The cells of the anterior pituitary gland synthesize and release: growth hormone, prolactin, thyroid stimulating hormone (Thyrotropin or TSH), luteinizing hormone (LH), and adrenocortictropic hormone (ACTH).  The cells of the Pars intermedia (part of anterior pituitary gland lying close to posterior pituitary) portion of the anterior pituitary gland secrete melanocyt- stimulating hormone (MSH) and are not normally active in adults.  The axons of the supraoptic nucleus and paraventricular nucleus extend from the hypothalamus through the infundibulum into the posterior pituitary gland.  ADH and Oxytocin are synthesized in the cell body of the supraoptic nucleus and paraventricular nucleus, respectively. They then travel along the axons to nerve terminals in the posterior pituitary gland and are released into the circulation upon depending on arrival of appropriate stimulus. Neurosecretory system linking the hypothalamus/pituitary gland. The neurosecretory system is shown in this diagram and links the hypothalamus with the anterior and posterior pituitary gland.  ADH and oxytocin are synthesized in the cell bodies of neurons located in the suparoptic and paraventricular nuclei (neurosecretory centre), and packaged into secretory granules.  The secretory granules are transported along the axon on microtubules at about a distance of 190 mm/day until they reach the nerve terminals (synapses) in the posterior pituitary gland.  They are released from the synapses into the pericapillary space and diffuse into the capillaries to be carried to target organs in the blood. Inhibiting hormones and releasing hormones from the hypothalamus which control the release of the hormones of the anterior pituitary gland are also synthesized in this manner and released at the nerve terminals and are transported to the endocrine cells of the anterior pituitary via the hypophyseal portal system. Hormones of the posterior pituitary ANTIDIURETIC HORMONE (ADH)  ADH is a 9 amino acid cyclic peptide hormone secreted when blood volume decreases. This decrease in volume causes increased electrolyte concentration, which increases osmotic 23  Dr Yasser Abdel-Wahab (Module Coordinator) pressure which also stimulates ADH secretion.  This stimulates release of ADH from nerve endings in the posterior pituitary which enter the blood.  ADH acts on the kidney tubules to increase water reabsorption from the tubular fluid.  This then increases blood volume and decreases osmotic pressure. OXYTOCIN Oxytocin is a small peptide hormone which:  Plays a key role in promoting contraction of the smooth muscles lining the uterus to induce labour at the end of pregnancy.  Causes contraction of myoepithelial cells around mammary glands and ducts to secrete milk for suckling infants. Hypothalamic releasing hormones / factors This flow diagram shows the hypothalamic releasing/inhibiting hormones and their actions on the hormone release from cells of the anterior pituitary gland (APG). There are 7 releasing/inhibiting hormones synthesised in the hypothalamus. AFFECTING RELEASE OF HYPOTHALAMUS APG HYPOTHALAMIC FACTORS + increases the release of the hypothalamic releasing/inhibiting hormone/factor. - inhibits the release of the hypothalamic releasing/inhibiting hormone/factor. LH/FSH-RH is also known as Gonadotropin-releasing hormone (GnRH). As mentioned earlier, somatostatin can also inhibit the release of TSH and GH. 24  Dr Yasser Abdel-Wahab (Module Coordinator) These releasing hormones/factors are synthesized in the cell bodies of neurosecretory cells of the hypothalamus, packaged into secretory granules and transported along the axon to the nerve terminals (synapses) and released into the hypophyseal portal system (blood) which carry them to the cells of the anterior pituitary gland Hormones of the anterior pituitary and their function There are 7 hormones synthesized and secreted from the endocrine cells of the anterior pituitary gland. These are: This diagram summarizes the main function of each of these hormones. Area affected Widespread Female mammary glands Thyroid gland Testes/Ovaries Testes/Ovaries Adrenal gland Melanocytes Regulatory pathways for hormones of anterior pituitary The regulation of secretion of the hypothalamic releasing/inhibiting hormones and the release of anterior pituitary (AP) hormones is highlighted in this flow diagram. The AP hormones which act on endocrine target tissues, cause increase in synthesis and release of endocrine hormones from these target tissue. E.g. TSH increases the production of T3 and T4 from thyroid gland. 25  Dr Yasser Abdel-Wahab (Module Coordinator) The increase in the circulating level of these hormones (like T3, T4) will cause negative feedback to either decrease the release of the hypothalamic releasing factors, or increase the release of inhibiting factors which will inhibit the release of the anterior pituitary hormone causing the effect (TSH). The endocrine hormones may also act directly on the anterior pituitary gland to inhibit secretion. GH can inhibits its own release by negative feedback on the AP gland and the hypothalamus. Also increased GH causes increased synthesis and release of Insulin-like growth factors (IGFs) from the liver. These IGFs feedback on the hypothalamus and anterior pituitary to increase GHRIH and decrease GRH thus inhibiting GH release. Prolactin feedback to increase PIH release from the hypothalamus to inhibit its release from the AP gland. Neural input can also alter the secretion of releasing and inhibiting factors from the hypothalamus, thereby regulating AP gland secretions. The Adrenal Glands The pyramid shaped adrenal glands are located on the top of each kidney and weigh about 7.5g. Their size can increase to meet adrenal hormone demand. They contain an outer region called the cortex which is rich in lipids, including cholesterol and fatty acids.  The hormones synthesized and secreted from the adrenal cortex are called adrenocorticoids or corticosteroids.  These corticosteroids include: o Mineralocorticoids (mainly aldosterone) o Glucocorticoids (mainly cortisol) o Sex hormones or gonadocorticoids (mainly androgens) The inner region of the adrenal gland is known as the medulla. The medulla contains cells called chromaffin cells which produce and secrete catecholamines (epinephrine (~80%), norepinephrine (~20%) and dopamine (