Induction of cultured bovine adrenocortical zona glomerulosa cell 17-hydroxylase activity by ACTH.
The induction of steroid 17-hydroxylase activity was examined in primary cultures of bovine adrenocortical zona glomerular cells. 17-Hydroxylase activity was determined by assaying the metabolism of [3H]pregnenolone to [3H]17-hydroxypregnenolone by high performance liquid chromatography (HPLC). Conversion of [3H]pregnenolone to [3H] progesterone and [3H]17-hydroxypregnenolone to [3H]17-hydroxyprogesterone was prevented by the addition of cyanoketone, an inhibitor of 3 beta-hydroxysteroid dehydrogenase. ACTH increased adrenal zona glomerulosa 17-hydroxylase activity 55-fold to 1750 pmoles/10(4) cells/2 h, an activity equivalent to that of ACTH-treated zona fasciculata cells. Maximal induction was seen after 4 days exposure to ACTH. The dose of ACTH which gave half-maximal induction was 0.25 nM. Previously, ACTH had been demonstrated to suppress bovine glomerulosa conversion of deoxycorticosterone to aldosterone by a steroid-induced oxygen-derived free radical process that was prevented by antioxidants. This process resulted in loss of the terminal cytochrome P-450 enzyme involved in aldosterone biosynthesis. However, induction of 17-hydroxylase activity is not affected by antioxidants or the addition of steroids, e.g. cortisol. ACTH-mediated induction of bovine zone glomerulosa 17-hydroxylase activity and suppression of glomerulosa aldosterone production results in effective conversion of functional glomerulosa cells to functional fasciculata cells. The actions of ACTH on glomerulosa 17-hydroxylase activity support the hypothesis of a steroid-induced functional zonation of the adrenal cortex.
D000302:Adrenal Cortex / Q000201:enzymology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D008054:Lipid Peroxides / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000096:biosynthesis*; D013250:Steroid Hydroxylases / Q000096:biosynthesis*
D008054:Lipid Peroxides; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase