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Thyroid gland The synthesis and release of thyroid hormone involves a number of steps 1. Uptake of iodide (ATP-dependent Na+, K+ATPase). 2. Activation and Organification of lodide (catalyzed by thyroperoxidase). 3. Coupling Reaction and Storage as Colloid (Iodide peroxidase or a "coupling enzyme" catalyzes the "coupling reaction). 4. Processing of TG and Release of Thyroid Hormone. Biological Actions of Thyroid Hormones Type bound to thyroxine-binding globulin (TBG) bound to transthyretin or "thyroxinebinding prealbumin" (TTR or TBPA) albumin unbound T4 (fT4) unbound T3 (fT3) Percent 70% 10-15% 15-20% 0.03% 0.3% Cardiovascular System Thyroid hormone enhances cardiac contractility and exerts a positive chronotropic effect on the heart, increasing heart rate by a mechanism that may involve more than a potentiation of the β-adrenergic effect. Intermediary Metabolism Thyroid hormone increases both lipolysis and lipogenesis, although lipogenesis is stimulated before lipolysis, due to early induction of malic enzyme (malate dehydrogenase), glucose-6phosphate dehydrogenase, and fatty acid synthase. Thyroid hormone lowers serum cholesterol levels. In liver, kidney, skeletal muscle, cardiac muscle, and adipose tissue, thyroid hormone stimulates Na+,K+ATPase gene expression and promotes thermogenesis. Growth and Maturation Thyroid hormone stimulates production of IGF-I directly (liver) and indirectly (via increased growth hormone, GH). Reproductive System Thyroid hormone increases total plasma androgen levels by increasing the production of testosteronebinding globulin (TeBG) by the liver. Video Thyroid Hormone Synthesis Vedieo Human Physiology - Thyroid Hormone Feedback and Function Calcitonin Calcitonin (also known as thyrocalcitonin) is a 32-amino acid linear polypeptide hormone that is produced in humans primarily by the parafollicular cells (also known as C-cells) of the thyroid. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH). More specifically, calcitonin lowers blood Ca2+ levels in two ways: Major effect: Inhibits osteoclast activity in bones Minor effect: Inhibits renal tubular cell reabsorption of Ca2+ and phosphate, allowing them to be excreted in the urine. The calcitonin receptor, found on osteoclasts, and in the kidney and regions of the brain, is a G protein-coupled receptor, which is coupled by Gs to adenylate cyclase and thereby to the generation of cAMP in target cells. Parathyroid gland Parathyroid hormone Parathyroid hormone parathyroid chief cells. secreted by Calcium: 1. Stimulates calcium release from bone, thereby increasing blood calcium 2. Stimulates osteoclasts, thus breaking down bone. 3. Stimulates calcium reabsorption in kidney 4. Stimulates activated vitamin D production in kidney Phosphate: 1. Stimulates Phosphate release from bones, thereby increasing blood Phosphate. 2. Inhibits Phosphate reabsorption in kidney, so more Phosphate excreted Overall, small net drop in serum Phosphate. Reproductive Hormones Testosterone Testosterone in plasma exists in two fractions: TeBG bound (44%) and nonTeBG-bound (56%). Biological Effects of Androgens The biological effects of androgenic hormones can be of two types: Reproductive (androgenic), i.e., promoting the primary and secondary sexual characteristics of a male. Non-reproductive, which includes anabolic effects. Reproductive (Androgenic) Effects 1. Testes At puberty, locally produced testosterone promotes spermatogenesis in the seminiferous tubules, although it is not known with certainty whether or not the Sertoli cells contain 5α-reductase. 2. Internal and External Genitalia In the fetus, testosterone causes differentiation of the Wolffian ducts into the male-type reproductive tract, and thereby rescues the tissue from pre-programmed destruction. The seminal vesicles, which differentiate from the Wolffian duct as a result of testosterone action, produce 5α-reductase2 from week 13-14 and become DHT-responsive after that; thus, development and function (but not appearance), may be regulated by DHT from the second trimester through adulthood. At puberty, however, the derivative of the genital tubercle (clitoris and penis) becomes responsive to testosterone, which enhances the male-type morphology by promoting growth of the existing structure. 3. Skin The hair follicles and sebaceous glands in the androgen sensitive areas of the skin and sebaceous glands throughout the body contain 5α-reductase type 1 and respond to DHT. At puberty, DHT stimulates the appearance and growth of terminal hair in certain androgen-sensitive regions of the body (face, chest, upper pubic triangle, nostrils, external ear). DHT stimulates the growth and secretory function (sebum production) of all sebaceous glands, and thus predisposes the skin to acne formation. Male pattern baldness 4. Voice Pitch Testosterone promotes enlargement of the larynx and thickening of the vocal folds (vocal cords), causing a lowering of the voice pitch. Non-reproductive Effects 1. Skeletal Muscle Testosterone promotes skeletal muscle growth by stimulating both hypertrophy and mitosis of myofibrils and increases the fast-twitch isoform of myosin heavy chain. The extent to which skeletal muscle mass can be increased is limited by the concentration of androgen receptors in the muscle that can be activated. . 2. Bone Androgens promote skeletal growth and maturation by a direct effect on bone tissue and by an indirect effect on growth hormone (GH) release. At puberty, the increasing levels of androgens stimulate the release of GH and result in accelerated endochondral growth of the epiphyses of long bones, which causes a doubling of height gain that is maximal at about mid- to late puberty. 3. Blood Volume Testosterone acts on the proximal tubule of the nephron to promote the reabsorption of K+, Na+, and Cl-, which, along with stimulated erythropoiesis, contributes to the androgenassociated increase in blood volume. 4. Erythropoiesis Androgens stimulate the production of erythropoietin by the kidney and, in part, cause an increase in hematocrit by this mechanism. This may explain why males have a higher hematocrit than females. 5. Adipose Tissue Androgens promote truncal-abdominal fat deposition and favor development of upper body obesity. 6. Liver Androgens cause a reduction in the plasma levels of testosterone-estradiol-binding globulin (TeBG), which results in an increased percentage of testosterone that is accessible for tissue uptake. Estrogen Estrogens are a group of compounds named for their importance in the estrous cycle of humans and other animals. Their name comes from the Greek words estrus = sexual desire and gen = to generate. The three major naturally occurring estrogens in women are estrone (E1), estradiol (E2), and estriol (E3). Estrone is produced during menopause, estradiol is the predominant form in nonpregnant females, and estriol is the primary estrogen of pregnancy. Structural function Promote formation of female secondary sex characteristics Accelerate metabolism Reduce muscle mass Increase fat stores Stimulate endometrial growth Increase uterine growth Increase vaginal lubrication Thicken the vaginal wall Maintenance of vessel and skin Reduce bone resorption, increase bone formation. Protein synthesis Increase hepatic production of binding proteins. Coagulation Increase circulating level of factors 2, 7, 9, 10, plasminogen. Decrease antithrombin III. Increase platelet adhesiveness. Lipid Increase HDL, triacylglycerol Decrease LDL, fat deposition Progesterone Progesterone also known as P4 (pregn-4-ene3,20-dione) is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis of humans and other species. Progesterone is sometimes called the "hormone of pregnancy", and it has many roles relating to the development of the fetus: Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female tract before fertilization occurs, though the receptor(s) as yet remain unidentified. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs. During implantation and gestation, progesterone appears to decrease the maternal immune response to allow for the acceptance of the pregnancy. Pancreatic hormones The pancreas is a glandular organ in the digestive system and endocrine system of vertebrates. It is an endocrine gland producing several important hormones including insulin, glucagon, somatostatin, and pancreatic polypeptide which circulate in the blood. Insulin Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans, specialized regions of the pancreas. Proinsulin is synthesized in the endoplasmic reticulum, where it is folded and its disulfide bonds are oxidized. It is then transported to the Golgi apparatus where it is packaged into secretory vesicles, and where it is processed by a series of proteases to form mature insulin. Mature insulin has 35 fewer amino acids; 4 are removed altogether, and the remaining 31 form the C-peptide. The C-peptide is abstracted from the center of the proinsulin sequence; the two other ends (the B chain and A chain) remain connected by disulfide bonds. Increased glycogen synthesis. Increased lipid synthesis. Increased esterification of fatty acids – forces adipose tissue to make fats (i.e., triglycerides) from fatty acid esters. Decreased proteolysis Decreased lipolysis Decreased gluconeogenesis Increased amino acid uptake – forces cells to absorbe circulating amino acids; lack of insulin inhibits absorption. Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1), which starts many protein activation cascades (2). These include translocation of Glut4 transporter to the plasma membrane and influx of glucose (3), glycogen synthesis (4), glycolysis (5) and triacylglycerol (6). Glucagon Glucagon, a peptide hormone secreted by the pancreas, raises blood glucose levels. The pancreas releases glucagon when blood sugar (glucose) levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream. Glucagon is a 29-amino acid polypeptide. Glucagon is generated from the cleavage of proglucagon secreted by pancreatic islet α cells. Glucagon generally elevates the amount of glucose in the blood by promoting gluconeogenesis and glycogenolysis. Glucose is stored in the liver in the form of glycogen, which is a polymer made up of glucose molecules. Liver cells (hepatocytes) have glucagon receptors. When glucagon binds to the glucagon receptors, the liver cells convert the glycogen polymer into individual glucose molecules, and release them into the bloodstream, in a process known as glycogenolysis. As these stores become depleted, glucagon then encourages the liver and kidney to synthesize additional glucose by gluconeogenesis. Glucagon turns off glycolysis in the liver, causing glycolytic intermediates to be shuttled to gluconeogenesis. Glucagon also regulates the rate of glucose production through lipolysis. Somatostatin Somatostatin (also known as growth hormone-inhibiting hormone (GHIH)) is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G proteincoupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin has two active forms produced by alternative cleavage of a single preproprotein: one of 14 amino acids, the other of 28 amino acids. In the anterior pituitary gland, the effects of somatostatin are: Inhibit the release of growth hormone (GH) (thus opposing the effects of Growth Hormone-Releasing Hormone (GHRH)) Inhibit the release of thyroid-stimulating hormone (TSH). Pineal body (epiphysis) Melatonin, chemically N-acetyl-5-methoxy tryptamine. In animals, melatonin is involved in the entrainment (synchronization) of the circadian rhythms of physiological functions including sleep timing, blood pressure regulation, seasonal reproduction, and many others. In addition, melatonin has antioxidant activity Stomach Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas. Causes chief cells to secrete pepsinogen, the zymogen (inactive) form of the digestive enzyme pepsin. Gastrin release is inhibited by: 1. The presence of acid (primarily the secreted HCl) in the stomach (a case of negative feedback). 2. Somatostatin also inhibits the release of gastrin, along with secretin, GIP (gastroinhibitory peptide), VIP (vasoactive intestinal peptide), glucagon and calcitonin. Ghrelin, the "hunger hormone", also known as lenomorelin (INN), is a peptide hormone produced by ghrelinergic cells in the gastrointestinal tract which functions as a neuropeptide in the central nervous system. Ghrelin regulating appetite. Ghrelin stimulates the release of growth hormone, increase in hunger, modulation of glucose and lipid metabolism, regulation of gastrointestinal motility and secretion, protection of neuronal and cardiovascular cells, and regulation of immune function. Neuropeptide Y (NPY) is a 36-amino acid neuropeptide that acts as a neurotransmitter in the brain and in the autonomic nervous system of humans; slight variations of the peptide are found in many other animals. In the autonomic system it is produced mainly by neurons of the sympathetic nervous system and serves as a strong vasoconstrictor and also causes growth of fat tissue. Increased food intake and decreased physical activity. It can be associated with obesity. Somatostatin is secreted at several locations in the digestive system: Delta cells in the pyloric antrum, the duodenum and the pancreatic islets Somatostatin released in the pyloric antrum travels via the portal venous system to the heart, then enters the systemic circulation to reach the locations where it will exert its inhibitory effects. In addition, somatostatin release from delta cells can act in a paracrine manner. Suppress release of gastrin, cholecystokinin (CCK), secretin, motilin, vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP), enteroglucagon. Lowers the rate of gastric emptying Reduces smooth muscle contractions and blood flow within the intestine. Histamine Enterochromaffin-like cells, located within the gastric glands of the stomach, release histamine that stimulates nearby parietal cells by binding to the apical H2 receptor. It stimulates gastric acid secretion Endothelins are 21-amino acid vasoconstricting peptides produced primarily in the endothelium having a key role in vascular homeostasis. Produced by X cells in the stomach and stimulates smooth muscle contraction of the stomach Duodenum (small intestine) Secretin is a peptide hormone produced in the S cells of the duodenum. Secretin helps regulate the pH of the duodenum by: (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate from the centroacinar cells and intercalated ducts of the pancreas. Secretin also stimulates bile production by the liver; the bile emulsifies dietary fats in the duodenum so that pancreatic lipase can act upon them. Meanwhile, in concert with secretin's actions, the other main hormone simultaneously issued by the duodenum, cholecystokinin, is stimulating the gallbladder to contract, delivering its stored bile for the same reason. The mature secretin peptide is a linear peptide hormone, which is composed of 27 amino acids and has a molecular weight of 3055. Cholecystokinin (CCK or CCK-PZ; from Greek chole, "bile"; cysto, "sac"; kinin, "move"; hence, move the bile-sac (gallbladder)) is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. Cholecystokinin, previously called pancreozymin, is synthesized and secreted by enteroendocrine cells (I cells) in the duodenum, the first segment of the small intestine. Its presence causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively, and also acts as a hunger suppressant.