Regulation of adrenal steroidogenesis by adrenaline: expression of cytochrome P450 genes.
The effect of adrenaline on the secretion of cortisol and cyclic AMP (cAMP) and on the accumulation of four different mRNAs encoding cholesterol side-chain cleavage cytochrome P450 (P450scc), 17 alpha-hydroxylase cytochrome P450 (P450(17 alpha)), 21-hydroxylase cytochrome P450 (P450c21) and 11 beta-hydroxylase cytochrome P450 (P450(11 beta)) was studied in bovine adrenocortical cells in primary culture and compared with the effects of ACTH. Treatment of cultured cells with adrenaline (1-100 mumol/l) showed a biphasic response in cortisol release over 1-24 h. Concentration of cAMP in the culture media increased from a basal level of < 0.06 pmol/dish to a maximal level of 40.14 +/- 8.9 pmol/dish with a half-maximal release of 20.07 pmol cAMP/dish in the medium reached 1.2 h after treatment with 10 mumol adrenaline/l. This stimulation resulted in an uniform increase in the levels of all four P450 mRNAs as revealed by Northern blot analysis. Increasing doses of adrenaline produced a maximal mRNA accumulation at a concentration of 10 mumol adrenaline/l. Incubation of the cells with 10 mumol adrenaline/l for 1-24 h produced a biphasic time-course with a half-maximal stimulation after about 5-6 h. Maximal stimulation with ACTH (100 nmol/l) caused different accumulations of the four mRNAs: P450sec mRNA increased twice as much and P450(17 alpha) mRNA six times as much as the accumulation of P450c21 mRNA and P450(11 beta) mRNA, which was about ten-fold over basal values. Propranolol totally blocked the stimulatory effect of adrenaline but not the effect of ACTH.(ABSTRACT TRUNCATED AT 250 WORDS)
Güse-Behling
H
H
Department of Internal Medicine, University of Ulm, Germany.
Ehrhart-Bornstein
M
M
Bornstein
S R
SR
Waterman
M R
MR
Scherbaum
W A
WA
Adler
G
G
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004837:Epinephrine / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006854:Hydrocortisone / Q000096:biosynthesis; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D013268:Stimulation, Chemical
D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; D006854:Hydrocortisone; D004837:Epinephrine