MECHANISMS OF NEUROENDOCRINE REGULATION

调查的重点是其性质和监管 促肾上腺皮质激素释放因子受体及其作用机制 CRF和其他ACTH分泌调节因子之间的相互作用。 A. CRF受体特性： 与1251-Tyr-oCRF交联的去污剂溶解的CRF受体 表明受体是一种单一的蛋白质， 分子量为67 kDa。 CRF受体的特征是 在不同的靶组织中相似，包括前部和 垂体和皮质的中间叶，杏仁核和 大脑的嗅球 B。 CRF受体调节：先前的研究表明， 垂体促肾上腺皮质激素释放因子受体下调伴随着 肾上腺切除术后血浆ACTH增加依赖于 下丘脑因素，如CRF和VP。 强制降解期间研究 显示在慢性炎症后血浆促肾上腺皮质激素一过性升高， 固定化。 随后的血浆ACTH下降， 持续存在的压力伴随着CRF受体下降- 垂体的调节和脱敏。 然而，在这方面， 体内垂体反应性以及增强效应 VP对CRF体外作用的影响， 监管机构之间互动的重要性 ACTH分泌的生理控制。 促肾上腺皮质激素释放因子受体 中间垂体和大脑在慢性 制动应激 C. ACTH调节剂的作用机制：先前的研究 表明VP对CRF作用的协同作用 涉及CRF刺激的cAMP产生的增强，表明 蛋白激酶C的激活是 的VP。 对分离的垂体细胞的研究表明， 内源性蛋白激酶C的作用消除了VP在 促肾上腺皮质激素 此外，VP显示刺激肌醇 磷酸盐形成和诱导蛋白激酶易位 C从胞质到膜室。

Investigation has focused on the properties and regulation of the corticotropin releasing factor receptors and the mechanism of interaction between CRF and other regulators of ACTH secretion. A. CRF receptor properties: Gel electrophoresis analysis of detergent-solubilized CRF receptors crosslinked with 1251-Tyr-oCRF indicated that the receptor is a single protein with a molecular weight of 67 kDa. The characteristics of the CRF receptor are similar in the different target tissues, including anterior and intermediate lobes of the pituitary and the cortex, amygdala and olfactory bulb of the brain. B. CRF receptor regulation: Previous studies have shown that pituitary CRF receptor down regulation that accompanies the increase in plasma ACTH following adrenalectomy is dependent on hypothalamic factors, such as CRF and VP. Studies during stress showed transient increases in plasma ACTH following chronic immobilization. The subsequent decrease in plasma ACTH in the continuous presence of stress is accompanied by CRF receptor down- regulation and desensitization of the pituitary. However, pituitary responsiveness in vivo as well as the potentiating effect of VP on CRF action in vitro are maintained emphasizing the importance of the interaction between regulators during physiological control of ACTH secretion. CRF receptors in the intermediate pituitary and brain are unchanged during chronic immobilization stress. C. Mechanism of action of ACTH regulators: Previous studies demonstrated that the synergistic effect of VP on CRF action involves potentiation of CRF-stimulated cAMP production suggesting that protein kinase C activation is part of the mechanism of action of VP. Studies in isolated pituitary cells showed that inhibition of endogenous protein kinase C abolishes the effects of VP in the corticotroph. In addition VP was shown to stimulate inositol phosphate formation and to induce translocation of protein kinase C from cytosol to the membrane compartment.