Darbeida H, Durand P
INRA, URA CNRS 1291, Mønnaie, France.
Biochem Biophys Res Commun. 1990 Feb 14;166(3):1183-91. doi: 10.1016/0006-291x(90)90991-u.
The present studies were undertaken to precise the mechanism through which glucocorticoids enhance the responsiveness of ovine adrenocortical cells to ACTH. Experiments using intact cells and crude adrenal membranes have shown that, at the level of the adenylate cyclase system, dexamethasone increases the number of ACTH receptors without modification of the catalytic subunit or of the GTP binding regulatory components Gs and Gi. Cells cultured with dexamethasone secreted more pregnenolone and more corticosteroids in response to 8-BrcAMP than did control cells. By contrast, dexamethasone did not increase corticosterone secretion by cells incubated in the presence of 22-(R)-hydroxycholesterol or of exogenous pregnenolone. Dexamethasone neither affected the incorporation of [14C] acetate into cellular cholesterol nor the amount of cholesterol present in mitochondria of unstimulated cells. However, dexamethasone-treated cells incubated in the presence of both 8-BrcAMP and aminoglutethimide exhibited higher amounts of mitochondrial cholesterol than control cells. These data indicate that dexamethasone enhances the number of cellular ACTH receptors together with increasing the cAMP-induced translocation of cholesterol from the cytoplasm into mitochondria and/or mitochondrial storage of cholesterol.
本研究旨在明确糖皮质激素增强绵羊肾上腺皮质细胞对促肾上腺皮质激素（ACTH）反应性的机制。使用完整细胞和粗制肾上腺膜进行的实验表明，在地塞米松作用下，腺苷酸环化酶系统层面上，地塞米松增加了促肾上腺皮质激素受体的数量，而催化亚基或GTP结合调节成分Gs和Gi未发生改变。与对照细胞相比，用地塞米松培养的细胞对8-溴环磷腺苷（8-BrcAMP）反应时分泌了更多的孕烯醇酮和皮质类固醇。相比之下，在22-(R)-羟基胆固醇或外源性孕烯醇酮存在的情况下，地塞米松并未增加细胞的皮质酮分泌。地塞米松既不影响[14C]乙酸盐掺入细胞胆固醇，也不影响未受刺激细胞线粒体中胆固醇的含量。然而，在8-溴环磷腺苷和氨鲁米特存在的情况下，经地塞米松处理的细胞线粒体胆固醇含量高于对照细胞。这些数据表明，地塞米松增加了细胞促肾上腺皮质激素受体的数量，同时增加了环磷腺苷诱导的胆固醇从细胞质向线粒体的转运和/或线粒体中胆固醇的储存。
