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Chapter 11

Chapter 11. The Endocrine System. Section 1. Introduction. The endocrine system : A signals transmission system composing of classic endocrine glands and some tissues as well as cells which have endocrine functions.

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Chapter 11

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  1. Chapter 11 The Endocrine System

  2. Section 1 Introduction

  3. The endocrine system :A signals transmission system composing of classic endocrine glands and some tissues as well as cells which have endocrine functions. • Hormone:A chemical substance produced by various endocrine cells in the body that controls and regulates the activity of certain cells or organs. • Neurohormone: chemical secreted by neurons into the blood.

  4. Classification of hormones • Peptide or protein hormones • Protein hormones –PTH, growth hormone, prolactin, etc. • Peptides - hypothalamic regulatory peptides, insulin , glucagon , etc. Amine hormones - Adr, NA,thyroid hormones (T3 and T4). • Steroid hormones • Sex hormones from the gonads and placenta. - estrogen, progesteron,testosteron • All the adrenal cortex hormones - cortisol, aldosterone，DHEA •  1,25 dihydroxy-Vit D3

  5. Characteristics of hormone actions • To transmit biological messages. - first messenger,second messenger,third messenger,cascade reaction • To selectively act on the target glands (organs, tissues or cells.) (specificity) - Each receptor is usually high specific for a single hormone. Affinity.

  6. To function with biological amplification The concentration of hormones in blood is just pg/ml~ μg/ml. - 0.1 g CRH → 1. 0g ACTH → 40 g Cortisol → 400 × • Interaction of hormones – competition, antagonism, cooperation and permissiveness.

  7. Permissiveness ：one hormone must be present in adequate amounts for the full exertion of another hormone’s effect. - In essence, the first hormone, by enhancing a target cell’s responsiveness to another hormone, ‘permit’ this other hormone to exert its full effect. - e.g. Cortisol increases the contraction effect of catecholamines on cardic muscles and vascular smooth muscles.

  8. The styles of hormones action on the targets • Telecrine： glands or specialized cells release chemicals into circulating blood which binds to distant target cells. • Paracrine : a cells secrete hormones that diffuse into the extra cellular fluid and affect neighboring cells. • Autocrine: a cell secretes hormones that affect the function of the same cell. • Neuroendocrine: neurons secretehormones (neurohormones) that reach circulating blood and influence the function of cells at another location.

  9. Mechanisms of hormone action • All hormones act binding to specific receptors located in target cells reversibly. • Nitrogen-containing hormones(exceptforthyroidhormone) binding to cell surface receptors(G-pro coupling receptor). Second messenger hypothesis • Steroid hormones binding to intracellular receptors. Regulating the transcription process of DNA. Gene regulation mechanism. • - Steroid hormones: cytoplasm receptor • - thyroidhormone: neucleus receptor Second messengers: cAMP, IP3/DG, Ca2+, cGMP

  10. AC-cAMP-PKA pathway

  11. PLC-IP3/DG-CaM/PKC pathway

  12. Steroid hormones Gene regulation mechanism. Gene regulation mechanism The gene expression hypothesis

  13. Section 2 The Hypothalamus and the Pituitary

  14. Anatomical connections The pituitary gland (anterior and posterior) and the hypothalamus form one of the important functional links between the endocrine system and CNS. • Hypothalamus-hypophysis unit • Hypothalamo-adenohypophysis system • Hypothalamo-neurohypophysis system

  15. Hypothalamus-hypophysis unit

  16. Neuroendocrine cells in hypothalamus - Magnocellular neuroendocrine cell, MgC - Parvocellular neuroendocrine cell, PvC Hypothalamic regulatory peptides ( HRP)Definition: Hormones (Peptides) isolated from Hypophysiotrophic area of the hypothalamus which exercise control over the pituitary gland.

  17. 9 kinds of HRP TRH :thyrotropin-releasing hormone, GnRH: gonadotropin-releasing hormone, CRH: corticotropin releasing hormone, GHRH : growth hormone releasing hormone, GHRIH,or somatostatin : growth hormone release- inhibiting hormone, PRF: prolactin releasing factor, PIF: prolactin release-inhibiting factor, MRF : melanophore-stimulating hormone releasing factor, MIF : melanophore-stimulating hormone release- inhibiting factor

  18. Adenohypophysis = anterior pituitary • Thyroid stimulating hormone, TSH • Adrenocorticotropic hormone, ACTH • Follicle stimulating hormone, FSH • Luteinizing hormone, LH • Growth hormone, GH • Prolactin , PRL • Melanophore stimulation hormone, MSH

  19. Neurohypophysis = posterior pituitary • The Oxytocin and ADH are synthesized within the superaoptic nucleus and paraventricular nucleus in hypothalamus • ADH – be discussed in the Chapter of Kidney. • Oxytocin – to facilitate the ejection of milk and the contraction of uterus.

  20. GH(hGH), somatotropin • To promote fission ( 分裂）and proliferation（ 增殖）of bone tissue, muscle tissue and the other tissues. • Protein metabolism:stimulates protein anabolism in many tissues. Fat metabolism:stimulates triglyceride breakdown and oxidation in adipocytes.Carbohydrate metabolism:increases the blood glucose. (GH is often said to have anti-insulin activity.)

  21. ▪In early life, GH↑↑→Gigantism ( 巨人症 ） GH↓↓→Dwarfism （侏儒症）or growth retardation ▪ In adults, GH↑↑→acromegaly( 肢端肥大症) Controlled by GHRH and GHRIH, and the negative feed back.

  22. PRL – to promote the growth of mammary glands and maintain milk production. • MSH- to promote synthesis of melanin(黑色素）in melanocytes ( 黑素细胞）.

  23. Section 3 Thyroid

  24. Thyroid gland–composed of follicles lined by simple cuboidal epithelium. - Follicular cells produce T4 (thyroxine ）& T3 ( tri-iodothyronine) - Parafollicular cells (C cells) produce calcitonin . The two principle raw materials for making thyroid hormones : - Tyrosines are provided from a large glycoprotein called thyroglobulin, which is synthesized by thyroid epithelial cells and secreted into the lumen of the follicle. - Iodine, or more accurately iodide (I-), is taken up from food.

  25. Hormonogenesis and Metabolism • Follicular cells actively transport iodide (I-) into cells. • I- diffuses across the apical surface into the follicle. • These cells also produce and store a glycoprotein called thyroglobulin.. • Inside the follicle an enzyme called thyroid peroxidase (TPO) catalyzes the conversion of iodide into active iodine (I2) for iodinating thyroglobulin

  26. I2 + thyroglobulin → MIT + DIT MIT + DIT → T3 DIT + DIT → T4 • In response to TSH, thyroglobulin is taken back into the follicular cell from the apical surface.. • T3 & T4 Thyroglobulin is then hydrolyzed into aa, MIT, DIT, T4, & T3. • T4, & T3 diffuse out of the follicular cell at the basal surface and into the tissue fluid. • Inside the target cell, T4 is converted to T3 by cytoplasmic deiodinase.

  27. Biological Functions of thyroid hormone • The mechanism of thyroid hormone act on the target cell • Thyroid gland secretes thyroxine (T4) and tri-iodothyronine (T3). • T3 enters the nucleus and binds to the receptor to turn on protein synthesis.

  28. Metabolic functions 1.Heat production (calorigenesis, 产热效应) – O2 consumption and BMR of target tissues are increased by administration of thyroid hormone, especially in liver,cardiac muscle and kidneys. It is related to high activity of Na+ - K+ pump. e.g.Hyperthyroidism: prefer cool and hate hot. Hypothyroidism: cold-intolerance

  29. 2.Substance metabolism • Proteins–THs act on nucleus receptor to activate DNA transcription and synthesis of mRNA, hence to promote the synthesis of proteins and enzymes. Positive nitrogen balance - Hyperthyroidism → Negative nitrogen balance. - Hypothyroidism →mucoprotein↑→myxedema • Carbohydrate–promote the absorption of glucose at small intestine, and glycogenolysis. As well as to inhibit glycogenesis, and to activate Ad, Glucagon ， cortisol and GH for the action of elevating glucose level in blood. So the action iselevating glucose level in blood.

  30. 4.Fat metabolism–to promote the oxidization of fatty acid and strengthen the effects of catecholamines and glucagon on lipolysis. • Plasma concentrations of cholesterol and triglycerides are inversely correlated with thyroid hormone levels • - one diagnostic indication of thyroid functions. • arteriosclerosis

  31. Effect on growth and development - Are essential for mental and physical development in human, especially for developing brain and bone tissues. e.g. cretinism (Congenital thyroid deficiency ). - In children, thyroid hormones ↓ →mental retardationand lower skeletal growth. - Newborn screening for congenital hypothyroidism. - To treat the cretinism by supplement of thyroid hormones just in the 3 months postnatal.

  32. Effects on CNS–THs s the number of receptors for E in E’s target cells, thereby increasing the effectiveness of E (permissive action),s the excitability of CNS. • Effect on cardiovascular system –THs s heart rate, cardiac contractility and cardiac output. They also promote vasodilation, which leads to enhanced blood flow to many organs. (permissive action)

  33. Symptoms of hyperthyroidism • Intolerance to heat. • Increased sweating. • high BMR • Mild to extreme weight loss. • Muscle weakness. Extreme fatigue. • Nervousness, irritability, insomnia • Anxiety and other psychic disorders. • Tremor of the hands • exophthalmos

  34. Hypothyroidism–too little hormone secreted. Symptoms of the hypothyroidism: – low BMR, lethargy, fatigue, hair loss, weight gain, little cold tolerance. - Myxedema – accumulation of mucoproteins and fluid in subcutaneous tissue • Cretinism – children

  35. Hypothalamic-pituitary-thyroid axis. Hypothalamus secretes TRH→ pituitary gland secretes TSH → thyroid gland secretes T4 and T3→ induce physiological functions • Auto-regulation of thyroid hormones - higher level of iodine inhibits uptake of iodine that is called Wolff-Chaikoff effect. • Autonomic nervous systemregulates the secretion of thyroid hormone. Control of thyroid hormone secretion

  36. Section 4 Calcium Homeostasis

  37. Regulation of serum Ca2+ level is achieved through the coordinated actions of following three hormones. • Parathyroid hormone, PTH - ↑Ca2+ and ↓Phosphate in blood. osteoclast - osteoblast • Calcitonin, CT –secreted by parafollicular cell C , ↓ Ca2+and ↓Phosphate in blood. • 1,25-(OH)-D3

  38. VD3 - a steroid hormone synthesized in the skin by the ultraviolet radiation, or available in diet. By hydroxylation in liver and kidney, VD3 is transformed to be the active 1,25(OH)2D3. • To promote the absorption of Ca 2+ at intestine. • To activate the osteoclast, ↑Ca2+ and in blood. • To activate the osteoblsat to calcificate bone tissue. • In concert with parathyroid hormone, vitamin D also enhances fluxes of calcium out of bone. acts also to increase blood concentrations of calcium.

  39. Section 5 The Adrenal Gland

  40. mineralocorticoid (aldosterone) glucocorticoid (cortisol) androgens( DHEA,dehydroepiandrosterone) The Adrenal Glandis composed of an outer layer of cortex and an inner core of medulla.

  41. ADRENAL CORTEX Hormones - Corticosteroids – Mineralocorticoids / aldosterone /salt balance  Essential to life – Glucocorticoids / cortisol/ fuel metabolism; response to injury  Long term protection against stress  Drugs – Androgens

  42. Biosynthesis • Cholesterol is the precursor for all of the steroids. • Different biosynthetic pathways and enzymatic systems are necessary.

  43. Physiological Effects of Glucocorticoids (GCs, cortisol) • Mechanism of Action – Cytoplasm receptor - gene expression

  44. Cellular mechanism of Glucocorticoid action Cytoplasm receptor - gene expression

  45. The most prevalent disorder involving glucocorticoids Cushing'sdisease or hyperadrenocorticism – Excessive levels of glucocorticoids. Addison's disease or hypoadrenocorticism – Insufficient production of cortisol, often accompanied by an aldosterone deficiency.

  46. Effectsonmetabolismofglucose -Stimulate glyconeogenesis, particularly in the liver. - Inhibite glucose uptake in muscle and adipose tissue. - Decrease the responsiveness of the muscles and adipose tissue to insulin. Increase the blood glucose Addisonism(hypocorticism):hypoglycemia Cushing’s disease:hyperglycemia

  47. Effectsonlipidmetabolism • In liver, GCs increase the activities of enzymes involved in fatty acid synthesis (lipogenic effect) and promote the secretion of lipoproteins. • In adipose tissue, GCs promote the mobilization of fatty acid,lipolysis or lipid oxidation . • hypercorticism:adipo-redistribution full-moon face and buffalo shoulder

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