Saez J M, Evain D, Gallet D
J Cyclic Nucleotide Res. 1978 Aug;4(4):311-21.
The role of the cyclic AMP-protein kinase system in mediating the steroidogenic effect of ACTH, prostaglandin E1 and dibutyryl cyclic AMP, induced similar stimulations of protein kinase activity, cyclic AMP was studied using human adrenal cells isolated from normal and adrenocortical secreting tumors. At high concentrations of ACTH, complete activation of protein kinase of normal adrenal cells was observed within 3 min, at the time when cyclic AMP production was slightly increased and there was still no stimulation of steroidogenesis. At supramaximal concentrations, ACTH, PGE1 and dibutyryl cyclic AMP and cortisol productions in adrenal cells isolated from normal and from one adrenocortical tumor. In one tumor in which the adenylate cyclase activity was insensitive to ACTH, the hormone was unable to stimulate protein kinase or steroidogenesis, but the cells responded to both PGE1 and dibutyryl cyclic AMP. In another tumor in which the adenylate cyclase was insensitive to PGE1, this compound also did not increase protein kinase activity or steroidogenesis, but both parameters were stimulated by ACTH and dibutyryl cyclic AMP. After incubation of normal adrenal cells with increasing concentrations of ACTH (0.01-100 nM) marked differences were found between cyclic AMP formation and cortisol production. However at the lowest concentrations of ACTH exerting an effect on steroid production a close linked correlation was found between protein kinase activation and cortisol production, but half-maximal and maximal cortisol production occurs at lower concentration of ACTH than was necessary to induce the same stimulation of protein kinase. Similar findings were found after incubating the adrenal cells with dibutyryl cyclic AMP (0.01-10 mM). The results implicate an important role of the cyclic AMP-protein kinase system during activation of adrenal cell steroidogenesis by low concentrations of steroidogenic compounds.
环磷酸腺苷 - 蛋白激酶系统在介导促肾上腺皮质激素（ACTH）、前列腺素E1和二丁酰环磷酸腺苷的类固醇生成作用方面发挥的作用，这些物质诱导了类似的蛋白激酶活性刺激，使用从正常肾上腺和肾上腺皮质分泌肿瘤中分离出的人肾上腺细胞对环磷酸腺苷进行了研究。在高浓度的ACTH作用下，正常肾上腺细胞的蛋白激酶在3分钟内完全激活，此时环磷酸腺苷的产生略有增加，且类固醇生成仍未受到刺激。在超最大浓度下，ACTH、前列腺素E1和二丁酰环磷酸腺苷以及从正常肾上腺和一个肾上腺皮质肿瘤中分离出的肾上腺细胞中的皮质醇生成情况。在一个腺苷酸环化酶活性对ACTH不敏感的肿瘤中，该激素无法刺激蛋白激酶或类固醇生成，但细胞对前列腺素E1和二丁酰环磷酸腺苷均有反应。在另一个腺苷酸环化酶对前列腺素E1不敏感的肿瘤中，该化合物也未增加蛋白激酶活性或类固醇生成，但这两个参数均受到ACTH和二丁酰环磷酸腺苷的刺激。用浓度不断增加的ACTH（0.01 - 100 nM）孵育正常肾上腺细胞后，发现环磷酸腺苷形成和皮质醇生成之间存在显著差异。然而，在对类固醇生成产生影响的最低浓度的ACTH作用下，发现蛋白激酶激活与皮质醇生成之间存在密切的关联，但半最大和最大皮质醇生成所需的ACTH浓度低于诱导相同蛋白激酶刺激所需的浓度。用二丁酰环磷酸腺苷（0.01 - 10 mM）孵育肾上腺细胞后也发现了类似的结果。这些结果表明，在低浓度类固醇生成化合物激活肾上腺细胞类固醇生成过程中，环磷酸腺苷 - 蛋白激酶系统起着重要作用。
