MECHANISMS OF NEUROENDOCRINE REGULATION

调查的重点是监管和行动 促肾上腺皮质激素释放因子受体及其相互作用 CRF与其他ACTH监管机构。 A.CRF受体调节。我们之前已经表明， 垂体受体下调和脱敏 伴随着血浆ACTH的增加，肾上腺切除术经常是 部分原因是下丘脑CRF分泌增加。研究项目： 大鼠下丘脑损伤实验表明，黄连素对大鼠下丘脑损伤的影响 肾上腺切除完全取决于下丘脑的因素。 糖皮质激素缺乏本身并不涉及，因为 生理剂量的皮质酮会减少CRF受体。 长期应激对血浆ACTH反应的脱敏作用 伴随着CRF受体下调和 CAMP反应对CRF的脱敏作用。然而，脑下垂体 体内反应性的维持或增强可能是由于 Saved/CRF受体和其他调节因子，主要是VP。脑区 糖皮质激素治疗期间CRF受体未发生变化 管理和压力。 B.ACTH的作用机制和相互作用 监管者。先前的研究表明，慢性肾衰的影响是 CAMP依赖而其他刺激增加ACTH分泌和 通过钙/磷脂增强CRF的模拟作用 依赖机制，蛋白激酶C的激活。 进一步的研究表明，促肾上腺皮质激素释放激素的作用 VP涉及CRG刺激的cAMP水平升高，这是由于 磷酸二酯酶抑制与蛋白激酶C依赖 腺苷酸环化酶组分的磷酸化。监管 促肾上腺皮质激素功能的改变也涉及花生四烯酸的双重作用 含有脂氧合酶和环氧合酶产物的酸性代谢物 分别具有刺激性和抑制性。中国的动力学研究 体外培养的垂体细胞表现出ACTH分泌的两个时相 CRF和cAMP非依赖性刺激；早期阶段 ACTH释放率增加，这独立于 细胞外钙，以及恒定分泌速度的晚期 CRF部分钙依赖，完全钙 对非cAMP依赖刺激的依赖性。

Investigation has focused on the regulation and actions of cortiocotropin releasing factor receptors and the interactions of CRF with other ACTH regulators. A. CRF receptor regulation. We have previously shown that pituitary receptor downregulation and desensitization that accompany the increase in plasma ACTH often adrenalectomy is partially due to increased hypothalamic CRF secretion. Studies in rats with hypothalamic lesions demonstrated that the effect of adrenalectomy is completely dependent on hypothalamic factors. Glucocorticoid deficiency per se is not involved since physiological amounts of corticosterone decrease CRF receptors. Desensitization of plasma ACTH responses during prolonged stress is accompanied by CRF receptor downregulation and desensitization of cAMP responses to CRF. However, pituitary responsiveness in vivo is maintained or increased probably due to spared/CRF receptors and other regulators, mainly VP. Brain CRF receptoors were unchanged during glucocorticoid administration and stress. B. Mechanisms of action and interaction between ACTH regulators. Previous studies have shown that the effect of CRF is cAMP dependent while other stimuli increase ACTH secretion and potentiate the simulation by CRF through calcium/phospholipid dependent mechanisms, with activation of protein kinase C. Further studies demonstrated that potentiation of CRF action by VP involves enhancement of CRG stimulated cAMP levels due to inhibition of phosphodiesterase, and protein kinase C dependent phosphorylation of a component of adenylate cyclase. Regulation of corticotroph function also involves dual effects of arachidonic acid metabolites, with lipooxygenase and cyclooxygenase products being stimulatory and inhibitory, respectively. Kinetic studies in cultured pituitary cells showed two phases of ACTH secretion by CRF and cAMP independent stimuli; an early phase with a rapid increase in ACTH release rate which is independent of extracellular calcium, and a late phase of constant secretion rate with partial calcium dependence for CRF, and complete calcium dependence for non-cAMP dependent stimuli.