Adrenaline stimulates cholesterol side-chain cleavage cytochrome P450 mRNA accumulation in bovine adrenocortical cells.
The effect of adrenaline on the accumulation of mRNA encoding cholesterol side-chain cleavage cytochrome P450 (P450scc) and cortisol secretion was studied in bovine adrenocortical cells in primary culture. Treatment of cultured cells with adrenaline resulted in a 2-fold increase in mRNA encoding P-450scc, as revealed by Northern blot analysis. Under these conditions the maximal stimulation with ACTH resulted in a 6-fold accumulation of mRNA encoding P450scc. The effect of adrenaline on the expression of P450scc was abolished by the beta-blocker propranolol, while propranolol had no effect on ACTH-induced P450scc mRNA accumulation. Adrenaline stimulated the secretion of cortisol in a dose-dependent manner with a median effective dose of 0.5 mumol/l. The adrenaline-stimulated cortisol secretion amounted to 42% of the effect of ACTH (0.1 nmol/l). Upon adrenaline treatment, cAMP concentration in the culture medium increased about 50-fold over the basal value. It is concluded that the stimulatory action of adrenaline upon cortisol formation requires beta-adrenergic receptors and is due, at least in part, to a cAMP-mediated increases in the accumulation of mRNA encoding P450scc.
Ehrhart-Bornstein
M
M
Department of Internal Medicine, University of Ulm, Germany.
Bornstein
S R
SR
Trzeclak
W H
WH
Usadel
H
H
Güse-Behling
H
H
Waterman
M R
MR
Scherbaum
W A
WA
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006854:Hydrocortisone / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D013268:Stimulation, Chemical
D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D011433:Propranolol; D000242:Cyclic AMP; D002786:Cholesterol Side-Chain Cleavage Enzyme; D006854:Hydrocortisone; D004837:Epinephrine