Regulation of ACTH secretion from corticotrophs: the interaction of vasopressin and CRF.
Regulation of ACTH secretion from corticotrophs: the interaction of vasopressin and CRF.
复制标题
促肾上腺皮质激素分泌 ACTH 的调节：加压素和 CRF 的相互作用。
DOI：
10.1111/j.1749-6632.1987.tb24952.x
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发表时间：
1987
影响因子：
5.2
通讯作者：
Vale,WW
中科院分区：
文献类型：
--
作者：
Bilezikjian,LM;Vale,WW
促肾上腺皮质激素的分泌受下丘脑合成和分泌因子的多重调节。促肾上腺皮质激素释放因子（CRF）对ACTH的分泌和合成都有作用，是主要的调节因子。其他因子是弱促分泌素或对CRF介导的分泌具有促进作用。后者包括血管加压素（AVP）、催产素、血管紧张素I1和猫回声。此外，外周来源的糖皮质激素对ACTH的分泌和合成起负反馈控制作用。在培养的大鼠垂体前叶细胞和垂体前叶原代细胞中均发现了CRF的特异性高亲和力受体。现有数据表明CRF的作用是由cAMP依赖性途径介导的。这种激素刺激完整细胞中cAMP的产生16 * 1 - 20和与垂体前叶质膜相关的腺苷酸环化酶活性。'^.在一个分泌ACTH的克隆细胞系AtT20细胞中，CRF显示出刺激cAMP依赖性蛋白激酶，21并且插入该蛋白激酶的抑制剂抑制ACTH分泌和POMC基因表达。[22]另一方面，AVP的作用还没有得到很好的描述。垂体前叶AVP受体的特性与肝细胞类似，AVP通过增强磷脂酶C催化的磷脂酰肌醇二磷酸（PIP2）的水解，刺激磷脂酰肌醇（PI）的更新。此外，在培养的大鼠垂体前叶细胞中，32P的刺激、PI的标记响应于AVP 2 '表明该激素在两种组织中的共同机制。PIP2的水解导致产生双重胞内信号：三磷酸肌醇（IP3）和甘油二酯（DAG），分别升高胞内Ca~（2+）和激活蛋白激酶C（PKC）。外源性添加的佛波醇酯，如佛波醇肉豆蔻酸酯乙酸酯（TPA）和合成的DAG，如二辛酰甘油（DiC8），直接激活PKC。33这些药物对ACTH分泌也有刺激作用。因此，它们已被用作确定AVP对促肾上腺皮质激素细胞的作用是否可能由PLC催化的P1P2水解途径介导的工具。
The secretion of ACTH is multihormonally regulated by factors synthesized and secreted by the hypothalamus. The primary control is mediated by corticotropin releasing factor (CRF), which has both secretory and synthetic effects on ACTH.'-9 Other factors are either weak secretagogues or have facilitatory actions on CRF-mediated secretion. Among the latter are vasopressin (AVP), oxytocin, angiotensin I1 and the cat echo la mine^.^*^ In addition, glucocorticoids of peripheral origin exert a negative feedback control on both ACTH secretion and synthe~ is.~.~*'" Specific high-affinity receptors for CRF have been demonstrated both in cultured rat anterior pituitary cells and anterior pituitary h~ mogenates."-'~ Available data suggest that the actions of CRF are mediated by the CAMP-dependent pathway.'" 20 This hormone stimulates CAMP generation in intact cells16* 1'-20 and adenylate cyclase activity associated with anterior pituitary plasma membrane^.'^.'^ In a clonal ACTH-secreting cell line, the AtT20 cells, CRF was shown to stimulate CAMP-dependent protein kinases, 21 and the insertion of the inhibitor of this protein kinase inhibited ACTH secretion and POMC gene expression. 22 The action of AVP, on the other hand, has not been so well characterized. Anterior pituitary receptors for AVP appear to have characteristics similar to those found in hepatocyte~~~-~~ where AVP stimulates phosphatidylinositol (PI) turnover by enhanc-ing phospholipase C-catalyzed phosphatidylinositol bisphosphate (PIP2) hydroly~ is.~~ Furthermore, the stimulation of 32P, labeling of PI in response to AVP in cultured rat anterior pituitary cells2'suggests a common mechanism for this hormone in both tissues. The hydrolysis of PIP2 results in the generation of dual intracellular signals, inositol trisphosphate (IP3) and diacylglycerol (DAG), which elevate intracellular Ca2+ and activate protein kinase C (PKC), re~ pectively.~~-~* Exogenously added phorbol esters, such as phorbol myristate acetate (TPA), and synthetic DAG, such as dioctanoylglycerol (DiC8), activate PKC directly. 33 These agents also have stimulatory effects on ACTH secretion. 34s35 Therefore, they have been used as tools to determine if the action of AVP on corticotrophs might be mediated by the PLC-catalyzed PI P2 hydrolysis pathway.