MECHANISMS OF NEUROENDOCRINE REGULATION

调查的重点是以下机构的规章和行动： 促皮质激素释放因子受体及其相互作用 CRF与其他ACTH调节剂。 A. CRF受体调节。 我们之前已经证明， 垂体受体下调和脱敏， 伴随着血浆ACTH的增加，肾上腺切除术往往是 部分原因是下丘脑CRF分泌增加。 研究 下丘脑损伤的大鼠表明， 肾上腺切除术完全依赖于下丘脑因素。 糖皮质激素缺乏症本身并不涉及， 生理量的皮质酮降低CRF受体。 长期应激时血浆ACTH反应的脱敏 伴有CRF受体下调， cAMP对CRF反应的脱敏。 然而，垂体 体内反应性维持或增加可能是由于 备用/CRF受体和其他调节剂，主要是VP。 大脑 CRF受体在糖皮质激素治疗期间无变化 管理和压力。 B。 ACTH的作用机制和相互作用 监管部门 以前的研究表明，CRF的作用是 cAMP依赖性，而其他刺激增加ACTH分泌， 通过钙/磷脂增强CRF的模拟作用 依赖机制，与蛋白激酶C的激活。 进一步的研究表明， VP涉及CRG刺激的cAMP水平的增强， 磷酸二酯酶和蛋白激酶C依赖性抑制 腺苷酸环化酶组分的磷酸化。 调控 促肾上腺皮质激素功能也涉及花生四烯酸的双重作用， 酸性代谢物，含脂加氧酶和环氧合酶产物 分别是刺激性的和抑制性的。 动力学研究 培养的垂体细胞表现出两个阶段的ACTH分泌， CRF和cAMP非依赖性刺激;早期阶段， 促肾上腺皮质激素释放速率增加， 细胞外钙和恒定分泌速率的晚期阶段 CRF部分钙依赖，完全钙依赖 对非cAMP依赖性刺激的依赖。

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.