Steroidogenesis in guinea pig adrenal cortex: effects of ACTH on steroid secretion and steroidogenic enzyme activities and expression.
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.
CHUL Research Center and Laval University, Centre Hospitalier de l'Université Laval, Sainte-Foy, Quebec, Canada.
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Provencher
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Tremblay
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Bélanger
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Bélanger
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000735:Androstenedione / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006168:Guinea Pigs; D006727:Hormone Antagonists / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D006727:Hormone Antagonists; D012333:RNA, Messenger; D000735:Androstenedione; C003582:11-hydroxyandrostenedione; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase