Endocrine Physiology 袁东智 e-mail：sanzhimao402@163.com qq：136888706 Tel：13980500441 Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University

Topics Introduction Neuroendocrinology Functions of other endocrine glands Thyroid hormone Regulation of calcium and phosphorus metabolism Insulin Glucocorticoid Catecholamine

Part 1 Introduction BC2000 Castration 1. Empirical endocrinology BC2000 Castration 1543 Vesalius, “pituata” → “pituitary” 1835 Graves disease 1855 Claud Bernard, “endocrine” Addison's disease 1889 Brown-Squard,   “ Brown-Séquard Elixir”

2. experimental endocrinology 1902 Bayliss & Starling, “secretin” 1905 Hardy, “hormone”

3. neuroendocrinology 1928 Ernest Sharrer neurosecretion， neuroendocrine 1949 Bargmann 1955 Harris 1960 Yalow, Berson radio-immunoassay, RIA 1977 Guillemin、Schally Nobel Prize 1949年 德国科学家 Bargmann 用组织染色法清晰显示出连接下丘脑细胞和神经垂体的神经纤维束。

4. neuroendocrine-immune network 1977’ Besedovskyn Did you find common features of these three systems?

General Principles  Contrast the terms endocrine, paracrine, and autocrine. Define the terms hormone, target cell, and receptor. Compare and contrast hormone actions exerted via plasma membrane receptors with those mediated via intracellular receptors. Understand the role of hormone-binding proteins. Understand the feedback control mechanisms of hormone secretion. Explain the effects of secretion, degradation, and excretion on plasma hormone concentrations. Understand the basis of hormone measurements and their interpretation.

Endocrine glands

Ⅰ.Definition endocrine（内分泌 ） endocrine gland （内分泌腺） endocrine system （内分泌系统） hormone（激素） 内分泌的来由 Discussion： Which concept／concepts are not clear to you?

Ⅰ.Definition 内分泌（endocrine ）是内分泌腺或内分泌细胞 将所产生的生物活性物质——激素，直接释放到体液中发挥作用的一种功能 。 内分泌腺又称无管腺 导管 汗腺 汗液 激素 分子 内分泌 细胞 毛细血管 血流

Endocrine V.S Exocrine Classic endocrine gland Transport mode

Endocrine glands

Endocrine system Consists of endocrine glands and diffused endocrine cells; A information transfer system; Coordinates the functions of diverse organs with nervous system. ps：与书上定义有异议

内分泌系统由经典的内分泌腺与能产生激素的功能器 官及组织共同构成，是发布信息整合机体功能的调节 系统。 经典内分泌腺 松果体 垂体 甲状腺 甲状旁腺 肾上腺 胰岛 卵巢 睾丸 具有内分泌功能的器官 下丘脑 心 肺 肝 肾 胃肠道 脂肪组织 ……

Function of endocrine system What are the differences between the functions of neuroregulation and humoral regulation？ Function of endocrine system maintenance of homeostasis regulation of metabolism growth and development regulation of reproduction

Hormone Hormone is a chemical substance secreted into the extracellular fluid by one or a group of cells and has a physiological control effect on other cells of the body. 激素（hormone）是由机体一些特殊细胞所分泌， 以体液为媒介在细胞间递送信息的化学信使 （chemical messengers）。

II. Transport modes of hormones telecrine paracrine autocrine endocrine

II. Transport modes of hormones intracrine neurocrine solinocrine

II. Transport modes of hormones

II. Transport modes of hormones 血中激素的存在方式：大多数为结合态 如甲状腺结合球蛋白，胰岛素类生长因子结合蛋白，肾上腺皮质类固醇结合球蛋白等。 结合态的意义： 1. 加速在血中的转运； 2. 激素暂时贮存的方式，延缓激素的清除。 结合的激素一般生物效能较差。血中还有一定量的游离激素分子，其生物效能较高。

IⅡ. Chemical Classification of Hormones 1. Proteins and peptides (synthesized from amino acids) 2. Amines (derivatives of tyrosine) 3. Lipid hormones steroid hormones fatty acid derivatives

Chemical types of hormone molecules （缩宫素） 多肽类

激素对靶细胞的作用机制概要

IV. Characteristics of Hormone Action 1.Specificity（特异性） Hormones act through specific receptors that define tissue selectivity and response. Target cells (tissues,organs,glands) Receptor (membrane, cytoplasm, nucleus) 交叉现象 Regulation of receptors: affinity, number down regulation up regulation

2. Action as a messenger（信使作用） First messenger membrane plasma Rs H Gs b g a GDP GTP ATP cAMP AC Protein PKA PDE 5`AMP ADP P Physiological activities Ri Gi Second messenger

Intracellular Receptor Hormone-receptor Complex 激素经激活细胞内多条信号转导途径产生调节效应 Gene Transcription

3. High efficiency（高效能性） Concentration in the blood: pg/ml, ng/ml CRH (0.1μg) ACTH (1 μg) → Glucocorticoids (40 μg) → Glycogen (6000 μg) → 激素能激发细胞内的生物放大效应 60,000 times!

4. Interaction of hormones（激素间的相互作用） Synergistic action（协同作用） Glucocorticoids, Glucagon, Epinephrine， GH → blood glucose↑ 激素升高血糖的协同效应

Antagonistic action（拮抗作用） Insulin → blood glucose↓ PGI2 → cAMP↑ → Platelet aggregation - + TXA2 → cAMP↓ Permissive action（允许作用）: A hormone, which has no effect by itself but is necessary for the full expression of the effects of another hormone, is said to have a permissive action.

Competitive action（竞争作用） epinephrine + thyroid hormone thyroid hormone Hormones given epinephrine Adipocyte 醛固酮是一种强盐皮质激素，在低浓度时 就有作用;孕酮对醛固酮受体有低亲和性结合， 因此，当孕酮以低浓度存在时，有弱盐皮质激素 效应，当以高浓度存在时，可与醛固酮竞争同一 受体，从而减弱醛固酮的效应。 Amount of fatty acids released no small amount large amount Competitive action（竞争作用） 醛固酮 V.S 孕激素

V. Regulation of hormone secretion 1. Biorhythm pulsatile release circadian rhythm Circadian rhythm of cortisol secretion

昼夜时间 血浆激素水平的脉冲式和日周期性变化

2. Effectors action on hormone levels （直接反馈调节） Endocrine gland St. Hormone Target tissues Response + - parathyroid gland PTH kidney bone [Ca2+] ↑ + - [Ca2+]

激素 内分泌腺 内分泌细胞 靶 细 胞 外周效应 多种刺激信号 （代谢信息、神经冲动等） 激素分泌的反馈调控

3. Influence of other hormones hypothalamus-adenohypophysis-target gland axes CNS Short- loop - Long- loop - Hypothalamus Adenohypophysis Target gland Hormone + - Ultrashort-loop - negative feedback

Positive feedback ovulation estradiol + Hypothalamus GnRH Adenohypophysis Positive feedback LH ovary ovulation estradiol

Summary Definition of endocrine system and hormorne 内分泌系统和激素的概念 Transport modes of hormones 激素的转运方式 Characteristics of hormone action 激素作用的一般特征 Regulation of hormone secretion 激素分泌的调节

Part 2 Neuroendocrinology What do you know about Neuroendocrinology？

hypothalamus hypophysis Neuroendocrine system neurohypophsis adenohypophysis

Hypothalamus-neurohypophysis system Hypothalamus—adenohypophysis system

Ⅰ. Hypothalamus-neurohypophysis system Vasopressin(VP) Oxytocin(OT) (antidiuretic hormone, ADH) magnocellular neuroendocrine cells(MgC) hypothalamohypophyseal tract 简略讲ADH的作用及调节（肾脏讲） diabetes insipidus （尿崩症）

What do they do, ADH and Oxytocin? -secreted in response to osmolarity pressure and to blood volume -kidney, to increase water reabsorption Oxytocin -released when an infant is suckling -mammary, to activate milk ejection -uterus, to stimulate contraction

Ⅱ. Hypothalamus—adenohypophysis system

1. Functional relationship between hypothalamus and adenohypophysis parvocellular neuroendocrine cells PvC MgC hypophysiotropic area HRP median eminence hypophyseal portal system HRP VP,OXT

下丘脑促垂体区： 肽能神经元 视前区、弓状核、腹内侧核、视交叉上核及室周核等 AL:垂体前叶；ARC:弓状核；BA:基底动脉；CRH:促肾上腺皮质激素释放激素；DA :多巴胺；GnRH:促性腺激素释放激素；GRH:生长激素释放激素；IC:颈内动脉；IL:垂体中间叶；MC:大脑中动脉；ME:正中隆起；PC:大脑中动脉；Peri:室周核；PL:垂体后叶；PV:室旁核；SO:视上核；SS:生长抑素

2. hypothalamic regulatory peptides ( HRP) HRP are secreted into the hypophyseal portal system by peptidergic neurons in hypophysiotrophic area of hypothalamus and control the secretion of anterior pituitary hormones. 下丘脑调节肽: 由下丘脑促垂体区肽能神经元 （小细胞神经元）分泌的肽类激素，主要作用 是调节腺垂体的分泌活动。 releasing hormone release-inhibiting hormone HRP

调节腺垂体功能的下丘脑调节肽 ____________________________________________________________ 种类 英文缩写 化学性质 主要作用 促甲状腺激素释放激素 TRH 3肽 促进TSH释放，也能刺激PRL释放 促性腺激素释放激素 GnRH 10肽 促进LH与FSH释放（以LH为主） 促肾上腺皮质激素释放激素CRH 41 肽 促进ACTH释放 生长素释放激素 GHRH 44肽 促进GH释放 生长素释放抑制激素 GHRIH 14肽 抑制GH释放，对LH、FSH 、 （生长抑素 ） TSH 、PRL及ACTH的分泌也有 抑制作用 促黑(素细胞)激素释放因子 MRF 促进MSH释放 促黑(素细胞)激素释放抑制因子 MIF 抑制MSH释放 催乳素释放因子 PRF 促进PRL释放 催乳素释放抑制因子 PIF 抑制PRL释放 __________________________________________________________

下丘脑-腺垂体激素与靶腺及外周器官的关系 请指出其中的促激素

Extrahypothalamic CNS 3. Regulation on hormones secreted by hypothalamus 1）Nervous regulation peripheral sensory inputs Extrahypothalamic CNS (monamines, peptides, ACh) neurotransmitter + or - peptidergic neurons 复杂、多样 Monamine TRH GnRH GHRH CRH PRF NE ↑ ↑ ↑ ↓ ↓ DA ↓ ↓ (-) ↑ ↓ ↓ 5-HT ↓ ↓ ↑ ↑ ↑

2) Humoral regulation hypothalamus-adenohypophysis-thyroid axes hypothalamus-adenohypophysis-adrenal cortex axes hypothalamus-adenohypophysis-gonad axes Long- loop - Short- Hypothalamus Anterior pituitary Target gland Hormone + Ultrashort-loop

hypothalamus-adenohypophysis-target gland axes 下丘脑-腺垂体-甲状腺轴 下丘脑-腺垂体-肾上腺轴 下丘脑-腺垂体-性腺轴

Summary （小细胞神经分泌系统） 下丘脑—腺垂体系统 垂体门脉系统 下丘脑 腺垂体 下丘脑调节肽 下丘脑调节肽 下丘脑—神经垂体系统 下丘脑—垂体束 VP、OXT 下丘脑—神经垂体系统 （大细胞神经分泌系统）

排卵前后雌激素对高位激素分泌的反馈调节