Wu Y W, Chik C L, Albertson B D, Linehan W M, Knazek R A
Developmental Endocrinology Branch, NICHD, NIH, Bethesda, Maryland.
Acta Endocrinol (Copenh). 1991 Jun;124(6):672-8. doi: 10.1530/acta.0.1240672.
Gossypol, an antifertility agent, has inhibitory actions on many membrane-associated enzymes, suggesting that this agent might have a generalized effect on cell membranes. This hypothesis was examined in the present study using membranes and dispersed cells prepared from human and rat adrenal glands. Four parameters were determined: microviscosity as measured by fluorescence polarization of human adrenal microsomal- and mitochondrial-enriched membranes, adrenal steroidogenic enzymes; and cAMP and cortisol responses to ACTH. It was found that gossypol increased the polarization constants of microsomes and mitochondria in a dose-dependent manner. Of the three adrenal enzymes tested, both 3 beta-hydroxysteroid dehydrogenase delta 5-delta 4 isomerase and 11-hydroxylase were inhibited by gossypol, but not 21-hydroxylase. Using intact human adrenocortical cells, high doses of gossypol also inhibited the ACTH-stimulated cAMP and cortisol levels. The in vivo corticosterone response to ACTH in rats subjected to chronic gossypol treatment was also found to be reduced. These findings suggest that gossypol has multiple effects on adrenal function. Its effects on membrane microviscosity, adrenal steroidogenesis, cAMP and corticosterone responses to ACTH stimulation probably occur through a generalized membrane effect.
棉酚是一种抗生育药物，对许多与膜相关的酶具有抑制作用，这表明该药物可能对细胞膜有广泛的影响。本研究使用从人和大鼠肾上腺制备的膜和分散细胞对这一假说进行了检验。测定了四个参数：通过人肾上腺富含微粒体和线粒体的膜的荧光偏振测量的微粘度、肾上腺类固醇生成酶；以及对促肾上腺皮质激素（ACTH）的环磷酸腺苷（cAMP）和皮质醇反应。结果发现，棉酚以剂量依赖的方式增加了微粒体和线粒体的偏振常数。在所测试的三种肾上腺酶中，3β-羟基类固醇脱氢酶δ5-δ4异构酶和11-羟化酶均受到棉酚的抑制，但21-羟化酶未受抑制。使用完整的人肾上腺皮质细胞，高剂量的棉酚也抑制了ACTH刺激的cAMP和皮质醇水平。还发现，接受慢性棉酚治疗的大鼠体内对ACTH的皮质酮反应降低。这些发现表明，棉酚对肾上腺功能有多种影响。其对膜微粘度、肾上腺类固醇生成、cAMP以及对ACTH刺激的皮质酮反应的影响可能是通过广泛的膜效应发生的。
