Klein N A, Andersen R N, Casson P R, Buster J E, Kramer R E
Department of Obstetrics and Gynecology, University of Tennessee, Memphis 38163.
J Steroid Biochem Mol Biol. 1992 Jan;41(1):11-20. doi: 10.1016/0960-0760(92)90219-9.
Results of previous studies indicated that insulin at levels comparable to those in humans during hyperinsulinemia decreased ACTH-stimulated cortisol and androstenedione secretion by bovine adrenal fasciculata-reticularis cells in primary culture. In the present studies this inhibitory action was examined further by comparing the effects of insulin on ACTH-stimulated corticosteroid secretion with its effects on 8-(4-chlorophenylthio)-cAMP (cpt-cAMP), forskolin- and [5val]angiotensin II (Ang II)-stimulated corticosteroid secretion. Effects on corticosteroid secretion were correlated with effects on cAMP accumulation and rates of cAMP production. Monolayers were incubated for 24 h in the absence or presence of each agonist alone or in combination with insulin. Insulin (1.7 x 10(-9) or 17.5 x 10(-9) M) caused about a 50% decrease in cortisol and androstenedione secretion in response to ACTH (10(-11) or 10(-8) M). Insulin also decreased ACTH-stimulated aldosterone secretion by cultured glomerulosa cells. Cpt-cAMP (10(-4) or 10(-3) M)-stimulated increases in cortisol and androstenedione secretion were inhibited by insulin, but to a lesser extent than those in response to ACTH. The inhibition of cpt-cAMP-stimulated steroid secretion was not related to increased degradation of the cyclic nucleotide. Increases in cortisol and androstenedione secretion caused by a submaximal concentration (10(-6) M) of forskolin were decreased 50-70% by insulin. In contrast, insulin failed to significantly affect cortisol or androstenedione secretion caused by a maximal concentration (10(-5) M) of forskolin. The secretory responses to Ang II (10(-8) M) were also unaffected by insulin. The effect of insulin to inhibit ACTH-stimulated steroid secretion was accompanied by a reduction in cAMP accumulation as well as an apparent inhibition of adenylate cyclase activation. These data indicate that the effect of insulin to attenuate ACTH-stimulated corticosteroid secretion results from both an inhibition of ACTH-stimulated adenylate cyclase activity and an antagonism of the intracellular actions of cAMP.
以往研究结果表明，在高胰岛素血症期间，与人类体内水平相当的胰岛素可降低原代培养的牛肾上腺束状带 - 网状带细胞中促肾上腺皮质激素（ACTH）刺激的皮质醇和雄烯二酮分泌。在本研究中，通过比较胰岛素对ACTH刺激的皮质类固醇分泌的影响及其对8 - （4 - 氯苯硫基） - 环磷酸腺苷（cpt - cAMP）、福斯可林和[5缬氨酸]血管紧张素II（Ang II）刺激的皮质类固醇分泌的影响，进一步研究了这种抑制作用。对皮质类固醇分泌的影响与对环磷酸腺苷（cAMP）积累和cAMP产生速率的影响相关。单层细胞在不存在或存在每种激动剂单独或与胰岛素联合的情况下孵育24小时。胰岛素（1.7×10⁻⁹或17.5×10⁻⁹ M）可使对ACTH（10⁻¹¹或10⁻⁸ M）反应的皮质醇和雄烯二酮分泌减少约50%。胰岛素还可降低培养的球状带细胞中ACTH刺激的醛固酮分泌。胰岛素可抑制cpt - cAMP（10⁻⁴或10⁻³ M）刺激的皮质醇和雄烯二酮分泌增加，但程度小于对ACTH反应的抑制程度。对cpt - cAMP刺激的类固醇分泌的抑制与环核苷酸降解增加无关。胰岛素可使次最大浓度（10⁻⁶ M）的福斯可林引起的皮质醇和雄烯二酮分泌增加减少50 - 70%。相比之下，胰岛素对最大浓度（10⁻⁵ M）的福斯可林引起的皮质醇或雄烯二酮分泌无显著影响。对Ang II（10⁻⁸ M）的分泌反应也不受胰岛素影响。胰岛素抑制ACTH刺激的类固醇分泌的作用伴随着cAMP积累的减少以及腺苷酸环化酶激活的明显抑制。这些数据表明，胰岛素减弱ACTH刺激的皮质类固醇分泌的作用源于对ACTH刺激的腺苷酸环化酶活性的抑制以及对cAMP细胞内作用的拮抗。
