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  • Title: Induction of cultured bovine adrenocortical zona glomerulosa cell 17-hydroxylase activity by ACTH.
    Author: Crivello JF, Gill GN.
    Journal: Mol Cell Endocrinol; 1983 Apr; 30(1):97-107. PubMed ID: 6301909.
    Abstract:
    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.
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