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Endocrine Physiology

Yuhong Tang (1471117590@qq.com) Department of Physiology, School of

Basic Medicine and Forensic Medicine, SCU

Topics n  Introduction

n  Neuroendocrinology

n  Functions of other endocrine glands •  Thyroid hormone •  Regulation of calcium and phosphorus metabolism •  Insulin •  Glucocorticoid •  Catecholamine

Schedule: 5-session lectures n  Introduction of endocrinology 1-session n  Neuroendocrinology 1.5-session n  Endocrine of thyroid hormone 0.5-session n  Regulation of calcium and phosphorus metabolism 0.5-session n  Endocrine of Insulin 0.5-session n  Endocrine of glucocorticoid 0.5-session n  Endocrine of adrenal gland 0.5-session

Part 1 Introduction

n  History

•  1543’ Vesalius, “pituata” → “pituitary”

•  1855’ Claud Bernard, “endocrine”

•  1889’ Brown-Squard

•  1902’ Bayliss & Starling

What is the first discovered hormone？

jejunum

HCl 1 2

4

atropine

vena

secretin

(no nerve)

•  1905’: Hardy, “hormone”

•  Discuss：实验项目1、2、3分别说明了什么？从实验项目4你可以得到什么结论？

3

1. experimental endocrinology 2. neuroendocrinology

n  Several stages of development

•  1928’ Ernest Sharrer neurosecretion， neuroendocrine

•  1949’ Bargmann • 1955’ Harris, •  1960’ Yalow, Berson radio-immunoassay, RIA •  1977’ Guillemin、Schally Nobel Prize for physiology and medicine

3. neuroendocrine-immune network

•  1977’ Besedovskyn

Did you find common features of these three systems?

Ⅰ.Definition（p528）

•  endocrine（内分泌 ）

•  endocrine gland （内分泌腺）

•  endocrine system （内分泌系统）

•  hormone（激素）

•  Discussion：

Which concept／concepts are not clear to you?

导管

汗腺

汗液

激素 分子

内分泌 细胞

毛细血管

血流

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

n  Endocrine glands 下丘脑是不是内分泌腺？

p530-531

n  Endocrine system

•  Consists of endocrine glands and diffused endocrine cells; •  A information transfer system; •  Coordinates the functions of diverse organs with nervous system.

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

……

•  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。（《生理学》，第3版，p530）

n  Function of endocrine system

•  maintenance of homeostasis •  regulation of metabolism •  growth and development •  regulation of reproduction

What are the differences between the functions of neuroregulation and humoral regulation？

n  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）。

n  Transport modes of hormones

telecrine paracrine autocrine neurocrine

neurohormone

solinocrine

intracrine 内在分泌

腔分泌

3. Lipid hormones

Ⅱ. Chemical Classification of Hormones

•  steroid hormones

•  sterol hormones

•  fatty acid derivatives

1. Proteins and peptides (synthesized from amino acids)

2. Amines (derivatives of tyrosine)

Chemical types of hormone molecules

（缩宫素）

多肽类

激素对靶细胞的作用机制概要

•  Target cells (tissues,organs,glands) •  Receptor (membrane, cytoplasm, nucleus)

Ⅲ. Characteristics of Hormone Action

•  Regulation of receptors: affinity, number

1.Specificity（特异性）

•  Hormones act through specific receptors that define tissue selectivity and response.

down regulation up regulation

2. Action as a messenger（信使作用）

membrane

plasma

Rs

H

Gs β γ α

GDP

GTP GDP ATP cAMP

β γ

α GTP

AC

Protein

PKA

PDE 5`AMP

ATP ADP

P Physiological activities

H

Ri

β γ Gi α

GDP

β γ

α GTP

GDP GTP

First messenger

Second messenger

Intracellular Receptor

Hormone-receptor Complex

Gene Transcription

3. High efficiency（高效能性）

•  Concentration in the blood: pg/ml, ng/ml CRH

(0.1ug)

Glucocorticoids (40ug)

→ ACTH (1ug) →

Glycogen

(6000ug) →

4. Interaction of hormones（激素间的相互作用）

•  Synergistic action（协同作用）

Glucocorticoids, Glucagon, Epinephrine， GH → 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.

• Antagonistic action（拮抗作用） Insulin → blood glucose↓

thyroid hormone

epinephrine +

thyroid hormone epinephrine

no small amount large amount

Hormones given

Adipocyte

Amount of fatty acids released

•  Competitive action（竞争作用）

Circadian rhythm of cortisol secretion

• pulsatile release 1. Biorhythm Ⅳ. Regulation of hormone secretion

• circadian rhythm

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+]

激素分泌的直接反馈调控

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）

3. Influence of other hormones •  hypothalamus-adenohypophysis-target gland axes

Long- loop

-

-

Short- loop

- Hypothalamus

Adenohypophysis

Target gland

Hormone

+

+

- Ultrashort-loop -

CNS

negative feedback

Hypothalamus

Adenohypophysis

ovary

estradiol

LH

GnRH

+

+ Positive

feedback

•  ovulation

排卵前后雌激素对高位激素分泌的反馈调节

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

hypothalamus-adenohypophysis-target gland axes

• 下丘脑—腺垂体—甲状腺轴

• 下丘脑—腺垂体—肾上腺皮质轴

• 下丘脑—腺垂体—性腺轴

n  hypothalamus-adenohypophysis-thyroid axes n  hypothalamus-adenohypophysis-adrenal

cortex axes n  hypothalamus-adenohypophysis-gonad axes

下丘脑—腺垂体—靶腺轴

4. Regulation by nervous system

ANS

adrenal medulla

+

hormone endocrine

gland

+ or -

autonomic ganglion

hormone

+

adeno -hypophysis

hypothalamus

. . .

target gland

. . .

•  hypothalamus integrates endocrine system with nerve centers

•  Innervation

•  Discussion：根据图示，请指出NS对ES的调节方式

神经支配

交感神经支配：甲状腺腺泡

肾上腺髓质

肾近球小体

胰岛A细胞

迷走神经支配： 胰岛B细胞

双重神经支配：胃肠道内分泌细胞

Summary

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

Part 2 Neuroendocrinology

What do you know about Neuroendocrinology？

Neuroendocrine system

hypothalamus

hypophysis neurohypophsis

adenohypophysis

n  Hypothalamus-neurohypophysis system n  Hypothalamus—adenohypophysis system

(antidiuretic hormone, ADH) Ⅰ. Hypothalamus-neurohypophysis system

hypothalamohypophyseal tract

•  magnocellular neuroendocrine cells(MgC)

n  Vasopressin(VP) n  Oxytocin(OXT)

n  diabetes insipidus （尿崩症）

下丘脑-神经垂体系统

•  ADH -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

n  What do they do, ADH and Oxytocin?

Ⅱ. Hypothalamus—adenohypophysis system

VP,OXT

MgC

PvC

1. Functional relationship between hypothalamus and adenohypophysis

•  1947’ Green & Harris

hypophyseal portal system

median eminence

HRP

HRP

parvocellular neuroendocrine cells

•  1955’ Harris 《垂体的神经控制》

颈内动脉发出垂体上动脉 ↓

正中隆起形成初级毛细血管网 ↓

汇合为垂体门静脉沿垂体柄向下 ↓

腺垂体形成次级毛细血管网

•  哺乳类动物的垂体门静脉系统:

•  初级血管网血管壁附近有丰富的神经末梢

•  1968’ Halasz hypophysiotrophic area

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

•  下丘脑促垂体区： 视前区、弓状核、腹内侧核、

视交叉上核及室周核等

•  肽能神经元

下丘脑-腺垂体系统

2. hypothalamic regulatory peptides ( HRP)

n  HRP are secreted into the hypophyseal portal system by peptidergic neurons in hypophysiotrophic area of hypothalamus and control the secretion of anterior pituitary hormones.

n  下丘脑调节肽: 由下丘脑促垂体区肽能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

adenohypophysis GH PRL MSH

TSH

thyroid

FSH LH ACTH

adrenal cortex

gonad

tropic hormone （促激素）

n  hormones secreted by adenohypophysis

n  thyrotropin-releasing hormone, TRH n  gonadotropin-releasing hormone, GnRH n  growth hormone release-inhibiting hormone, GHRIH, or somatostatin, SS n  corticotropin-releasing hormone, CRH n  growth hormone releasing hormone, GHRH n  pituitary adenylate cyclase activating

polypeptide, PACAP (垂体腺苷酸环化酶促多肽) n  ghrelin, ( 生长素/生长激素释放肽)

Ronger Guillemin vs Andrew Schally

HRP structure (peptides)

main functions

TRH 3 TSH↑, PRL ↑ GnRH 10 FSH ↑, LH ↑ CRH 41 ACTH ↑ GHRH GHRIH

44 14

GH ↑ GH↓,TSH↓,LH↓,FSH↓ ACTH↓,PRL↓, insulin↓

PIH PRF

dopamine

PRL ↓ PRL ↑

MRF MIF

MSH ↑ MSH ↓

____________________________________________________________

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

__________________________________________________________

调节腺垂体功能的下丘脑调节肽

HRP Structure (peptides)

Main functions

TRH 3 TSH↑, PRL↑ GnRH 10 FSH↑, LH↑ CRH 41 ACTH↑ GHRH GHRIH

44

14

GH↑ GH↓, TSH↓, LH↓, FSH↓ ACTH↓, PRL↓, insulin↓

PIH PrRP / PRF

dopamine 31

PRL↓ PRL↑

PACAP 27/38 LH↑, PRL↑, GH↑, ACTH↑

Ghrelin 28 GH↑

peptidergic neurons

3. Regulation on hormones secreted by hypothalamus

1）Nervous regulation

peripheral sensory inputs (monamines,

peptides, ACh)

Extrahypothalamic CNS

neurotransmitter + or -

Monamine TRH GnRH GHRH CRH PRF

NE ↑ ↑ ↑ ↓ ↓ DA ↓ ↓ (-) ↑ ↓ ↓ 5-HT ↓ ↓ ↑ ↑ ↑

复杂、多样

2) Humoral regulation

Long- loop

-

-

Short- loop

- Hypothalamus

Anterior pituitary

Target gland

Hormone

+

+

- Ultrashort-loop -

n  hypothalamus-adenohypophysis-thyroid axes n  hypothalamus-adenohypophysis-adrenal cortex axes n  hypothalamus-adenohypophysis-gonad axes

• 下丘脑—腺垂体系统

垂体门脉系统

下丘脑调节肽 下丘脑 腺垂体

Summary （小细胞神经

分泌系统）

下丘脑 神经垂体 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）

下丘脑调节肽

References n  Basic concepts in physiology Charles Seidel ，北京大学医学出版社，2002 n  Physiology, 6th Berne RM et al, 北京大学医学出版社, 2013 n  Textbook of Medical Physiology Guyton & Hall, 12th , 2011 n 人体生理学（上、下册），第3版，姚泰主编， 人民卫生出版社 2001 n  近代生理学发展简史

吴襄编著 高等教育出版社 1996