CHUL Research Center and Laval University, Centre Hospitalier de l'Université Laval, Sainte-Foy, Quebec, Canada.
J Steroid Biochem Mol Biol. 1992 Dec;43(8):855-62. doi: 10.1016/0960-0760(92)90312-7.
In this study, we investigated guinea pig adrenal steroidogenesis, specially, C19 steroid production. Analysis of adrenal steroids by high performance liquid chromatography and gas chromatography indicated the presence of androstenedione and 11β-hydroxyandrostenedione. Adrenal androstenedione and 11β-hydroxyandrostenedione levels were stimulated by ACTH administration while only 11β-hydroxyandrostenedione was increased in plasma. In vitro studies using adrenal cortex cells in primary culture confirmed that 11β-hydroxyandrostenedione is the major C19 steroid secreted. The chronic treatment of guinea pig with ACTH stimulated all adrenal post-pregnenolone enzyme activities and decreased P 450c17 mRNA levels while P 450scc, 3β-hydroxysteroid dehydrogenase and P450c11 mRNAs remained unaffected. Treatment of adrenal cells in primary culture with ACTH for 72 h changed the distribution of steroids secreted and decreased 21-hydroxylase activity while 17α-hydroxylase and 17,20-lyase activities were increased favoring C19 steroid production. In ACTH-treated cells, the mRNA levels for P450c21 and P450c17 increased and reached a peak at 18 h. Our data indicate that treatment with ACTH stimulates adrenal steroidogenic capacity by increasing steroid secretion and causes transcriptional and post-transcriptional effects on steroidogenic enzymes gene expression. Finally, the direct action of steroids on steroid production by adrenal cells in primary culture was investigated. Our data indicate that steroids themselves increase C19 steroid synthesis and inhibit glucocorticoid production without affecting gene expression for steroidogenic enzymes.
在这项研究中，我们研究了豚鼠肾上腺类固醇生成，特别是 C19 类固醇的产生。高效液相色谱和气相色谱分析肾上腺类固醇表明存在雄烯二酮和 11β-羟雄烯二酮。ACTH 给药后，肾上腺雄烯二酮和 11β-羟雄烯二酮水平升高，而血浆中仅 11β-羟雄烯二酮增加。使用原代培养的肾上腺皮质细胞的体外研究证实，11β-羟雄烯二酮是主要的 C19 类固醇分泌物。ACTH 对豚鼠的慢性治疗刺激了所有肾上腺孕烯醇酮后酶的活性，并降低了 P450c17mRNA 水平，而 P450scc、3β-羟甾脱氢酶和 P450c11mRNA 不受影响。用 ACTH 处理原代培养的肾上腺细胞 72 小时改变了分泌类固醇的分布，并降低了 21-羟化酶活性，而 17α-羟化酶和 17,20-裂合酶活性增加，有利于 C19 类固醇的产生。在 ACTH 处理的细胞中，P450c21 和 P450c17 的 mRNA 水平增加，并在 18 小时达到峰值。我们的数据表明，ACTH 治疗通过增加类固醇分泌刺激肾上腺类固醇生成能力，并对类固醇生成酶基因表达产生转录和转录后效应。最后，研究了类固醇对原代培养的肾上腺细胞类固醇生成的直接作用。我们的数据表明，类固醇本身增加了 C19 类固醇的合成，并抑制了糖皮质激素的产生，而不影响类固醇生成酶的基因表达。
