1. The Endocrine System Introduction to Endocrinology

5. Adrenal glands Divided into 2 regions; secrete hormones that influence the body's metabolism, blood chemicals, and body characteristics, as well as influence the part of the nervous system that is involved in the response and defense against stress. Hypothalamus Activates and controls the part of the nervous system that controls involuntary body functions, the hormonal system, and many body functions, such as regulating sleep and stimulating appetite. Ovaries and testicles Secrete hormones that influence female and male characteristics, respectively. Pancreas Secretes a hormone (insulin and glucagon ) that controls the use of glucose by the body. Parathyroid glands Secrete a hormone that maintains the calcium level in the blood. Pineal body Involved with daily biological cycles. Pituitary gland Produces a number of different hormones that influence various other endocrine glands. Thymus gland Plays a role in the body's immune system. Thyroid gland Produces hormones that stimulate body heat production, bone growth, and the body's metabolism.

6. Evolution of Endocrine Systems Most animals with well-developed nervous and circulatory systems have an endocrine system. The vertebrate endocrine system consists of glands and diffuse cell groups scattered in epithelial tissues . More than fifty different hormones are secreted. Endocrine glands arise during development for all three embryologic tissue layers (endode rm, mesoderm, ectoderm). The type of endocrine product is determined by which tissue layer a gland originated in. Glands of ectodermal and endodermal origin produce peptide and amine hormones; mesodermal-origin glands secrete hormones based on lipids.

7. Types of secretion Endocrine secretion – substance released by cell into blood stream that affects distant cells Exocrine secretion – substance released by cell into a duct that leads to epithelial surface (onto skin or into gut). Action doesn’t depend on receptors in target tissue. Endocrine and exocrine secretions are glandular secretions ; they come from specialized secretory cells that are clumped together to form a gland. Secretion may have several sites of action simultaneously .

8. Distinguish different communication pathways Paracrine: Cell produces hormone that stimulates or inhibits itself Cell produces hormone that stimulates or inhibits its neighbor Cells sit side by side. One has hormone on surface, the other has the receptor. Juxtacrine :

9. The term hormone is derived from Greek verb which means to excite First was used by William Bayliss and Ernest Starling in 1902 to describe the action of secretin (hormone of duodenum) Based more on physiological effects hormones are signal molecules, products of glandular cells, which are secreted into the the internal medium, mostly into the blood. Acting target cells and in turn they respond with changing of functional and nutritional status

11. H Gland (secretory cell) M Metabolic organ R Target tissue (target cell) effects Receptor Our endocrine system is a collection of glands that produce hormones that regulate our body's growth, metabolism, and sexual development and function. The hormones are released into the bloodstream and transported to tissues and organs throughout your body.

13. The endocrine system establishes as adequate hormone concentration at the level of receptors on target cells.

14. Functions Structure Hormone acts on thyroid follicle cells to stimulate throid hormone synthesis 2 proteins:  is 96 amino acids;  is 112 Thyrotropin (TSH) stimulates cells of adrenal gland to increase steroid synthesis and secretion polypeptide = 39 amino acids Corticotropin (ACTH) pigmentation  polypeptide = 13 amino acids  polypeptide = 18 amino acids  polypeptide = 12 amino acids Melanocyte-stimu- lating hormone (MSH) general anabolic stimulant, increases release of insulin-like growth factor-I (IGF-I), cell growth and bone sulfation protein of 191 amino acids Growth hormone (GH) responds to osmoreceptor which senses extracellular [Na + ], blood pressure regulation, increases H 2 O readsorption from distal tubules in kidney polypeptide of 9 amino acids CYFQNCPRG (C's are disulfide bonded) Vasopressin uterine contraction, causes milk ejection in lactating females, responds to suckling reflex and estradiol, lowers steroid synthesis in testes polypeptide of 9 amino acids CYIQNCPLG (C's are disulfide bonded) Oxytocin Pituitary Hormones

15. acts on lactotrope to release prolactin this may be TRH Prolactin-releasing factor (PRF) acts on gonadotrope to release LH and FSH polypeptide of 10 amino acids Gonadotropin-releasing factor (GnRF) acts on corticotrope to release ACTH and  -endorphin (lipotropin) protein of 41 amino acids Corticotropin-releasing factor (CRF) Hypothalamic Hormones acts on lactotrope to inhibit prolactin release may be derived from GnRH precursor, 56 amino acids Prolactin-releasing inhibiting factor (PIF) ovarian follicle development and ovulation, increases estrogen production; acts on Sertoli cells of semiferous tubule to increase spermatogenesis 2 proteins:  is 96 amino acids;  is 120 Follicle-stimulating Hormone (FSH) increases ovarian progesterone synthesis, luteinization; acts on Leydig cells of testes to increase testosterone synthesis and release and increases interstitial cell development 2 proteins:  is 96 amino acids;  is 121 Luteinizing hormone (LH) protein of 197 amino acids protein of 197 amino acids Prolactin

16. acts as a vasodilator protein of 37 amino acids, product of the calcitonin gene derived by alternative splicing of the precursor mRNA in the brain Calcitonin gene-related peptide (CGRP) produced in parafollicular C cells of the thyroid, regulation of Ca 2+ and P i metabolism protein of 32 amino acids Calcitonin responds to TSH and stimulates oxidations in many cells iodinated dityrosin derivatives Thyroxine and triiodothyronine Thyroid Hormones stimulates TSH and prolactin secretion polypeptide of 3 amino acids Thyrotropin-releasing factor (TRF) inhibits GH and TSH secretion polypeptide of 14 and 28 amino acids Somatostatin stimulates GH secretion protein of 40 and 44 amino acids Growth hormone releasing factor (GRF)

17. secreted from duodenum at pH values below 4.5, stimulates pancreatic acinar cells to release bicarbonate and H 2 O 27 amino acids Secretin produced by stomach antrum, stimulates acid and pepsin secretion, also stimulates pancreatic secretions 17 amino acids Gastrin inhibits secretion of gastric acid, enhances insulin secretion polypeptide of 42 amino acids Glucose-dependent insulinotropic polypeptide (GIP) originally called gastric inhibitory polypeptide potentiates glucose-dependent insulin secretion, inhibits glucagon secretion, inhibits gastric emptying Two forms: 31 amino acids, GLP-1(7-37) and 30 amino acids, GLP-1(7-36)amide Glucagon-like peptide 1 (GLP-1) formerly called enteroglucagon Hormones and Peptides of the Gut regulation of Ca 2+ and P i metabolism, stimulates bone resorption thus increasing serum [Ca 2+ ], stimulates P i secretion by kidneys protein of 84 amino acids Parathyroid hormone (PTH) Parathyroid Hormone

18. suppresses glucose-induced insulin secretion, inhibits bicarbonate and protein secretion from pancreas 36 amino acids Pancreatic Polypeptide, PP CNS function in pain (nociception), involved in vomit reflex, stimulates salivary secretions, induces vasodilation antagonists have anti-depressant properties 11 amino acids Substance P a member of the tachykinin family that includes neurokinin A (NKA) and neurokinin B (NKB) inhibits release and action of numerous gut peptides, e.g. CKK, gastrin, secretin, motilin, GIP; also inhibits insulin and glucagon secretion from pancreas 14 amino acid version Somatostatin produced by hypothalamus and GI tract, relaxes the GI, inhibits acid and pepsin secretion, acts as a neurotransmitter in peripheral autonomic nervous system, increases secretion of H 2 O and electrolytes from pancreas and gut 28 amino acids Vasoactive intestinal peptide (VIP) controls gastrointestinal muscles 22 amino acids Motilin stimulates gallbladder contraction and bile flow, increases secretion of digestive enzymes from pancreas 33 amino acids Cholecystokinin, CCK

19. increases glycogenolysis, regulation of gastrointestinal activity polypeptide of 36 amino acids Pancreatic polypeptide produced by  -cells of the pancreas, increases lipid mobilization and glycogenolysis in order to increase blood glucose levels polypeptide of 29 amino acids Glucagon inhibition of glucagon and somatotropin release 14 amino acid version Somatostatin produced by  -cells of the pancreas, increases glucose uptake and utilization, increases lipogenesis, general anabolic effects disulfide bonded dipeptide of 21 and 30 amino acids Insulin Pancreatic Hormones homology to EGF and binds to the EGF receptor (EGFR) 2 peptides: 78 amino acid truncated form and 84 amino acid form with 6 additional N-terminal amino acids Amphiregulin effects on hypothalamic function in appetite, controls feeding behavior and energy homeostasis, levels increase during starvation to induce food intake 36 amino acids 6 receptors Neuropeptide Tyrosine, NPY inhibits gastric motility by inhibiting cholinergic neurotransmission, inhibits gastric acid secretion 36 amino acids Peptide Tyrosine Tyrosine, PYY

20. maturation and function of male secondary sex organs steroid; testosterone Androgens (testicular) implantation of ovum and maintenance of pregnancy steroid; progesterone Progestins (ovarian) maturation and function of female secondary sex organs steroids; estradiol and estrone Estrogens (ovarian) Gonad Hormones produced in ovarian corpus luteum, inhibits myometrial contractions, secretion increases durin g gestation 2 proteins of 22 and 32 amino acids Relaxin inhibition of FSH secretion 1 protein (  is 134 amino acids;  is 115 and 116 amino acids Inhibins A and B acts like prolactin and GH protein of 191 amino acids Placental lactogen activity similar to LH 2 proteins:  is 96 amino acids;  is 147 Chorionic gonadotropin mimic action of progesterone steroids Progestins maintenance of pregnancy steroids Estrogens Placental Hormones

21. responsible for essential hypertension through stimulated synthesis and release of aldosterone from adrenal cells polypeptide of 8 amino acids derived from angiotensinogen (present in the  2 -globin fraction of plasma) which is cleaved by the kidney enzyme renin to give the decapeptide, angiotensin I, the C-terminal 2 amino acids are then released (by action of angiotensin-converting enzyme, ACE) to yield angiotensin II Angiotensin II Liver Hormones lipid mobilization, arteriole contraction tyrosine derivative Norepinephrine (noradrenalin) glycogenolysis, lipid mobilization, smooth muscle contraction, cardiac function derived from tyrosine Epinephrine (adrenalin) Adrenal Medullary Hormones maintenance of salt balance steroids; aldosterone Mineralocorticoids diverse effects on inflammation and protein synthesis steroids; cortisol and corticosterone Glucocorticoids Adrenal Cortical Hormones

22. regulation of circadian rhythms N -acetyl-5-methoxytryptamine Melatonin Pineal Hormones released from heart atria in response to hypovolemia, acts on outer adrenal cells to decrease aldosterone production; smooth muscle relaxation several active peptides cleaved from a 126 amino acid precursor Atrial natriuretic peptide (ANP) Cardiac Hormones responsible for maintenance of calcium and phosphorous hoemostasis, increases intestinal Ca 2+ uptake, regulates bone mineralization derived from 7-dehydrocholesterol Calcitriol [1,25-(OH) 2 -vitamin D 3 ] Kidney Hormones

24. Hormones are grouped into three classes based on their structure: Steroids P eptides A mines

25. Steroids Steroids are lipids derived from cholesterol. Steroid hormones are secreted by the gonads, adrenal cortex, and placenta.

26. Structure of some steroid hormones and their pathways of formation

27. Peptides and Amines Peptides are short chains of amino acids; most hormones are peptides. They are secreted by the pituitary, parathyroid, heart, stomach, liver, and kidneys. Amines are derived from the amino acid tyrosine and are secreted from the thyroid and the adrenal medulla. Solubility of the various hormone classes varies.

28. Mechanisms of Hormone Action The endocrine system acts by releasing hormones that in turn trigger actions in specific target cells. Receptors on target cell membranes bind only to one type of hormone. More than fifty human hormones have been identified; all act by binding to receptor molecules. The binding hormone changes the shape of the receptor causing the response to the hormone. There are two mechanisms of hormone action on all target cells. Nonsteroid Hormones or Hormones with Cell Surface Receptors Steroid Hormones or Hormones with Intracellular Receptors

29. Nonsteroid Hormones (water-soluble) or Hormones with Cell Surface Receptors Protein and peptide hormones, catecholamines and prostaglandins find their receptors decorating the plasma membrane of target cells. Binding of hormone to receptor initiates a series of events which leads to generation of so-called second messengers within the cell (the hormone is the first messenger ). The second messengers then trigger a series of molecular interactions that alter the physiologic state of the cell. Synonym signal transduction .

31. Several distinctive variations in receptor structure

32. Second Messenger Systems Consider what would happen if, late at night, you noticed a building on fire … Second messenger Examples of hormones which utilize this system Cyclic AMP Epinephrine and norepinephrine, luteinizing hormone, follicle stimulating hormone, thyroid – stimulating hormone, calcitonin, parathyroid hormone, antidiuretic hormone Protein kinase activity Insulin, growth hormone, prolactin, oxytocin, erythropoietin, several growth factors Calcium and/or phosphoinositides Epinephrine and norepinephrine, angiotensin II, antidiuretic hormone, gonadotropin-releasing hormone, thyroid-releasing hormone Cyclic GMP Atrial naturetic hormone, nitric oxide.

33. Second messengers activate other intracellular chemicals to produce the target cell response

37. Steroid Hormones or Hormones with Intracellular Receptors Receptors for steroid and thyroid hormones are located inside target cells, in the cytoplasm or nucleus, and function as ligand-dependent transcription factors . T he hormone-receptor complex binds to promoter regions of responsive genes and stimulate or inhibit transcription from those genes. T he mechanism of action of steroid hormones is to modulate gene expression in target cells

40. Steroid hormones bind, once inside the cell, to the nuclear membrane receptors, producing an activated hormone-receptor complex. The activated hormone-receptor complex binds to DNA and activates specific genes, increasing production of proteins.

41. Endocrine Systems and Feedback Cycles The endocrine system uses cycles , negative feedback and a ntagonistic pairs of hormones to regulate physiological functions. Negative feedback regulates the secretion of almost every hormone. Cycles of secretion maintain physiological and homeostatic control. These cycles can range from hours to months in duration.

44. Biological Cycles Cycles involve hibernation, mating behavior, body temperature and many other physiological processes. Rhythms or cycles that show cyclic changes on a daily (or even a few hours) basis are known as circadian rhythms . Many hormones, such as ACTH-cortisol, TSH, and GH show circadian rhythms. The menstrual cycle is controlled by a number of hormones s ecreted in a cyclical f ashion. Thyroid secretion is usually higher in winter than in summer. Childbirth is hormonally controlled, and is highest between 2 and 7 AM. Internal cycles of hormone production are controlled by the hypothalamu s , specifically the suprachiasmic nucleus (SCN). According to one model, the SCN is signaled by messages from the light-detecting retina of the eyes. The SCN signals the pineal gland in the brain to signal the hypothalamus, etc.

45. The Nervous and Endocrine Systems There is a stalk links the pituitary to the hypothalamus, which controls r elease of pituitary hormones. The hypothalamus contains neurons that control releases from the anterior pituitary. Seven hypothalamic hormones are released into a portal system connecting the hypothalamus and pituitary, and cause targets in the pituitary to release eight hormones.

46. The location and roles of the hypothalamus and pituitary glands