Iwasaki Y, Aoki Y, Katahira M, Oiso Y, Saito H
First Department of Internal Medicine, Nagoya University School of Medicine, Showa-ku, Japan.
Biochem Biophys Res Commun. 1997 Jun 18;235(2):295-9. doi: 10.1006/bbrc.1997.6785.
We investigated non-genomic mechanisms of glucocorticoid negative feedback regulation on pituitary corticotroph cells using the AtT20 mouse corticotroph tumor cell line. A synthetic glucocorticoid dexamethasone (100 nM) potently suppressed forskolin-induced cAMP generation, adrenocorticotropin (ACTH) secretion, and proopiomelanocortin gene expression. When de novo gene expression was inhibited by actinomycin D (1 microM), dexamethasone still suppressed cAMP efflux and ACTH release, although less potently. Interestingly, under the same conditions, pretreatment of the cells with pertussis toxin (50 ng/ml) completely abolished the suppressive effect of dexamethasone on both parameters. These results suggest that non-genomic and genomic mechanisms are involved in the glucocorticoid negative regulation of ACTH expression, and a pertussis toxin-sensitive GTP-binding protein might, at least partly, participate in the non-genomic effect.
我们使用AtT20小鼠促肾上腺皮质激素瘤细胞系，研究了糖皮质激素对垂体促肾上腺皮质激素细胞负反馈调节的非基因组机制。合成糖皮质激素地塞米松（100 nM）能有效抑制福斯高林诱导的环磷酸腺苷（cAMP）生成、促肾上腺皮质激素（ACTH）分泌及阿黑皮素原基因表达。当放线菌素D（1 microM）抑制从头基因表达时，地塞米松仍能抑制cAMP外流和ACTH释放，尽管效力较弱。有趣的是，在相同条件下，用百日咳毒素（50 ng/ml）预处理细胞可完全消除地塞米松对这两个参数的抑制作用。这些结果表明，非基因组和基因组机制均参与了ACTH表达的糖皮质激素负调节，且一种对百日咳毒素敏感的GTP结合蛋白可能至少部分参与了非基因组效应。
