Chang F H, Bourne H R
Department of Pharmacology, University of California, San Francisco 94143.
Endocrinology. 1987 Nov;121(5):1711-5. doi: 10.1210/endo-121-5-1711.
Glucocorticoids regulate responsiveness of many different cells and tissues to hormones that act by stimulating adenylyl cyclase. In a rat pituitary cell line, GH3, exposure to dexamethasone (150 mM for 72 h) doubled the specific activity of adenylyl cyclase in membrane extracts, whether the enzyme was stimulated by guanine nucleotides, vasoactive intestinal peptide, or forskolin. Dexamethasone treatment of GH3 cells also caused a 5-fold increase in RNA encoding the alpha-chain of Gs (alpha s) as well as a 2-fold increase in membrane-bound alpha s-polypeptide, measured by either of two assays: 1) Biochemical complementation of the alpha s deficiency of S49 lymphoma cyc- membranes in vitro; 2) Cholera toxin-catalyzed ADP ribosylation of 45- and 52-kilodalton alpha s-polypeptides. These observations suggest that glucocorticoid-induced enhancement of adenylyl cyclase activity in GH3 cells is mediated, at least in part, by increased expression of alpha s.
糖皮质激素调节许多不同细胞和组织对通过刺激腺苷酸环化酶起作用的激素的反应性。在大鼠垂体细胞系GH3中,暴露于地塞米松(150 mM,持续72小时)使膜提取物中腺苷酸环化酶的比活性增加了一倍,无论该酶是由鸟嘌呤核苷酸、血管活性肠肽还是福斯可林刺激。用地塞米松处理GH3细胞还导致编码Gsα链(αs)的RNA增加了5倍,以及膜结合的αs多肽增加了2倍,这是通过两种测定方法之一测量的:1)体外对S49淋巴瘤cyc-膜的αs缺陷进行生化互补;2)霍乱毒素催化的45千道尔顿和52千道尔顿αs多肽的ADP核糖基化。这些观察结果表明,糖皮质激素诱导的GH3细胞中腺苷酸环化酶活性增强至少部分是由αs表达增加介导的。