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1、Neuroendocrine system The HPG axisThe HPT axisThe HPA axisThe endocrine system differs from most of the other organ systems of the body - the various glands are not anatomically connected; however, they do form a system in the functional sense. Nervous system performs short term crisis managementEnd
2、ocrine system regulates long term ongoing metabolic Endocrine communication is carried out by endocrine cells releasing hormonesAlter metabolic activities of tissues and organs Target cellsParacrine communication involves chemical messengers between cells within one tissueEndocrine versus Nervous sy
3、stem“Here in this well-concealed spot, almost to be covered with a thumbnail, lies the very main spring of primitive existence vegetative, emotional, reproductive on which with more or less success, man has come to superimpose a cortex of inhibitions.”Cushing (1932) rostal caudalBoth human PVN and S
4、ON contain about 50.000 neurons. Almost all vasopressinergic SON neurons project to the posterior pituitary thus influencing plasma levels. In the PVN there are 3 different types of vasopressin producing neurons. Some take part in the HPA-axis, some project to the neuropituitary, some to other brain
5、 areas. HypothalamusParvocellular neurosecretory cell (PvC)神经内分泌小细胞 Hypophysiotrophic area, HTA下丘脑促垂体区 调节腺垂体内分泌活动Magnocellular neurosecretory cell (MgC)神经内分泌大细胞 视上核、室旁核 神经垂体激素催产素、血管加压素 神经垂体激素运载蛋白I, II (Neurophysin I, II) 神经肽:脑啡肽、内啡肽、神经肽YThe Hypothalamus - Hormones and Releasing FactorsProlactin Rele
6、asing Hormone (PRH)Prolactin Inhibiting Hormone (PIH)Thyrotropin Releasing Hormone (TRH)Corticotropin Releasing Hormone (CRH)Gonadotropin Releasing Hormone (GnRH)Growth Hormone Releasing Hormone (GHRH)Growth Hormone Inhibiting Hormone (GHIH)促黑素细胞激素释放促黑素细胞激素释放/ /抑制因子抑制因子(melanophore-stimulating hormo
7、ne releasing factor, MRF; melanophore-stimulating hormone release-inhibiting factor, MIF)可能是可能是催产素催产素裂解出来的两裂解出来的两种小分子肽种小分子肽Regulation of hypothalamic hormones神经调节神经调节: 单胺类递质: DA, NE, 5-HT 肽类物质: 脑啡肽、-内啡肽、神经降压素、P物质、VIP下级激素的反馈效应下级激素的反馈效应Releases 9 important peptide hormonesAll 9 bind to membrane recept
8、ors and use cyclic AMP as a second messengerAnterior pituitary originates from epithelium; posterior pituitary from neural tissueHypophysis = pituitarySubdivided into the pars distalis, pars intermedia and pars tuberalisThe anterior lobe (adenohypophysis) At the median eminence, neurons release regu
9、latory factors through fenestrated capillaries- Releasing hormones- Inhibiting hormonesThe Pituitary Gland - Anterior Pituitary HormonesMSH (pars intermedia )The Pituitary Gland - Anterior Pituitary Hormones The Pituitary Gland - Posterior Pituitary HormonesContains axons of hypothalamic nervesneuro
10、ns of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) manufacture antidiuretic hormone (ADH = vasopressin, AVP), oxytocin (OXT) and Neurophysin (NP) ADH decreases the amount of water lost at the kidneys, elevates blood pressureOXT stimulates contractile cells in mammary glands, stimul
11、ates smooth muscle cells in uterusTransportation:NP-1 + OT; NP-2 + VPin axoplasm of the neurons fibersRelease: ExocytosisPosterior Pituitary and hormones The structural and chemical characteristics of AVP and OXT The cyclical peptides differ in only 2 amino acid positions Both contain disulphide bri
12、dges between Cysteine residues (半胱氨酸残基) at positions 1 and 6.Regulation of ADH secretionosmolality secretionIncreased extracellular fluid osmolarity reduces size of osmoreceptors located in hypothalamus, which in turn stimulates ADH secretion blood volume secretionADH release is also controlled by c
13、ardiovascular reflexes in response to blood volume (atrial receptors) /pressure changesOXTSynthesis: SON, PVNSecretion: Parturition, lactation, coitionFunction:- Contraction of the uterus* induces labor contraction* reduces postpartum bleeding- Contraction of myoepithelial cells in the breast stimul
14、ates milk let-downRegulation- Neuroendocrine reflex (Milk ejection reflex) * Suckling- Positive feedback- Acute stress (-) OTX secretion * Levels of sex steroidsReview: Regulation by Negative FeedbackHormone Effects on Gene ActivityThree Methods of Hypothalamic Control over the Endocrine SystemThyro
15、id stimulating hormone (TSH)Triggers the release of thyroid hormonesThyrotropin releasing hormone promotes the release of TSHAdrenocorticotropic hormone (ACTH)Stimulates the release of glucocorticoids by the adrenal glandCorticotrophin releasing hormone causes the secretion of ACTHFollicle stimulati
16、ng hormone (FSH)Stimulates follicle development and estrogen secretion in females and sperm production in malesLeutinizing hormone (LH)Causes ovulation and progestin production in females and androgen production in malesGonadotropin releasing hormone (GnRH) promotes the secretion of FSH and LHHormon
17、es of the adenohypophysisProlactin (PRL)Stimulates the development of mammary glands and milk productionGrowth hormone (GH or somatotropin)Stimulates cell growth and replication through release of somatomedins or IGFGrowth-hormone releasing hormone (GH-RH)Growth-hormone inhibiting hormone (GH-IH)Hor
18、mones of the adenohypophysisMelanocyte-stimulating hormone (MSH)May be secreted by the pars intermedia during fetal development, early childhood, pregnancy or certain diseasesStimulates melanocytes to produce melaninTypes -MSH, -MSH(人), -MSHEffect 黑素细胞 (melanophores) 黑色素生成,使黑色素颗粒在细胞内分散 可能参与调节GH、醛固酮、
19、CRH、胰岛素、LH等分泌Regulation MIF MRFPro-opiomelanocortin (POMC,阿黑皮素原阿黑皮素原)a precursor hormone with 241 amino acid residues from corticotrophs in anterior pituitary,also synthesized by other tissues, e.g. placenta, GIprecursor for ACTH, -lipotropin (-LPH), -lipotropin (-LPH), -endorphin, N-terminal peptide, MSH (-MSH within ACTH, -MSH within -LPH, and -MSH within N-Peptide)Pro-opiomelanocortin (POMC) - a precursor polypeptide, synthesized from the 285-aa polypeptide precursor, pre-pro-opiomelanocortin (pre-POMC), by the removal of a 44-aa signal peptide sequence during translation.