Mattson M P, Mrotek J J
Steroids. 1985 Jul;46(1):619-37. doi: 10.1016/0039-128x(85)90026-1.
Using cultured Y-1 mouse adrenal tumor cells which produce 20 alpha-hydroxy-4-pregnen-3-one (20-DHP), it was found that 0.01 mM corticosterone and deoxycorticosterone increased basal and inhibited ACTH-induced 20-DHP production during consecutive 30 and 120 min incubations. Steroid effects were concentration-dependent and reversible. Six other steroids tested did not stimulate 20-DHP production and varied in ability to inhibit ACTH-stimulated steroidogenesis. Experiments demonstrated that 20-DHP production following treatment with cholera toxin, N,0'-dibutyryl cyclic AMP (dbcAMP), or pregnenolone was not inhibited by exogenous steroids. Corticosterone (0.01 mM) increased basal and inhibited ACTH-induced intracellular cyclic AMP (cAMP) production. Cytochalasin D, a microfilament perturbing agent, inhibited steroid-stimulated 20-DHP production, suggesting that ACTH and steroid stimulation mechanisms were similar. These findings taken together suggest that exogenous steroids can alter steroidogenesis by modifying plasma membrane adenylate cyclase activity.
利用能产生20α-羟基-4-孕烯-3-酮（20-DHP）的培养Y-1小鼠肾上腺肿瘤细胞，发现在连续30分钟和120分钟的孵育过程中，0.01 mM的皮质酮和脱氧皮质酮增加了基础20-DHP的产生，并抑制了促肾上腺皮质激素（ACTH）诱导的20-DHP产生。类固醇的作用具有浓度依赖性且是可逆的。所测试的其他六种类固醇并未刺激20-DHP的产生，且在抑制ACTH刺激的类固醇生成的能力方面存在差异。实验表明，用霍乱毒素、N,0'-二丁酰环磷酸腺苷（dbcAMP）或孕烯醇酮处理后20-DHP的产生不受外源性类固醇的抑制。皮质酮（0.01 mM）增加了基础细胞内环状磷酸腺苷（cAMP）的产生，并抑制了ACTH诱导的cAMP产生。细胞松弛素D是一种微丝干扰剂，它抑制了类固醇刺激的20-DHP产生，这表明ACTH和类固醇的刺激机制相似。综合这些发现表明，外源性类固醇可通过改变质膜腺苷酸环化酶活性来改变类固醇生成。
