Dexamethasone inhibits corticotropin-induced accumulation of CYP11A and CYP17 messenger RNAs in bovine adrenocortical cells.

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Trzeciak WH, LeHoux JG, Waterman MR, Simpson ER

Dexamethasone inhibits corticotropin-induced accumulation of CYP11A and CYP17 messenger RNAs in bovine adrenocortical cells.

Mol Endocrinol. 1993 Feb;7(2):206-13. doi: 10.1210/mend.7.2.8385739.

PubMed ID

8385739 [ View in PubMed

]

Abstract

The effect of dexamethasone on ACTH-induced accumulation of CYP11A and CYP17 mRNAs was studied in bovine adrenocortical cells in primary culture. The cells were treated with either ACTH (1 microM) or the adenylate cyclase activator forskolin (25 microM) and/or dexamethasone (100 nM). The accumulation of CYP11A and CYP17 mRNAs was evaluated by Northern blot analysis with the use of [alpha-32P]deoxy-CTP-labeled bovine CYP11A and CYP17 cDNAs. Chloramphenicol acetyltransferase (CAT) activity was monitored in bovine adrenocortical cells transfected with recombinant plasmids containing either CYP11A or CYP17 regulatory regions coupled to the CAT reporter gene and treated with forskolin and/or dexamethasone. Dexamethasone treatment of the cells cultured in the presence of ACTH or forskolin resulted in about 50% suppression of both CYP11A and CYP17 mRNA accumulation, with a concomitant fall in cortisol secretion to about 60% of the stimulated value. The effects of dexamethasone on accumulation of CYP11A and CYP17 mRNAs and cortisol secretion were blocked by pretreatment of the cells with RU 486 (100 nM), while RU 486 had no effect on forskolin-induced accumulation of either mRNA or cortisol secretion. Dexamethasone also inhibited the forskolin-induced expression of the transfected CYP11A- or CYP17-CAT constructs in bovine adrenocortical cells. The inhibitory effect of dexamethasone was greatly reduced by cotreatment of the transfected cells with RU 486. It is concluded that dexamethasone inhibits the ACTH-induced accumulation of CYP11A and CYP17 mRNAs at a transcriptional level and that the effect of dexamethasone is mediated by the glucocorticoid receptor.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Dexamethasone	Steroid 17-alpha-hydroxylase/17,20 lyase	Protein	Humans	Unknown	Inhibitor	Details
Dexamethasone acetate	Steroid 17-alpha-hydroxylase/17,20 lyase	Protein	Humans	Unknown	Inhibitor	Details