Regulation of adrenal steroidogenesis by adrenaline: expression of cytochrome P450 genes

J Endocrinol. 1992 Nov;135(2):229-37. doi: 10.1677/joe.0.1350229.

Abstract

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)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex / cytology
  • Adrenal Cortex / drug effects
  • Adrenal Cortex / metabolism*
  • Adrenocorticotropic Hormone / pharmacology
  • Animals
  • Blotting, Northern
  • Cattle
  • Cells, Cultured
  • Cyclic AMP / biosynthesis
  • Cytochrome P-450 Enzyme System / genetics*
  • Epinephrine / pharmacology*
  • Gene Expression Regulation
  • Hydrocortisone / biosynthesis
  • Male
  • RNA, Messenger / analysis
  • Stimulation, Chemical

Substances

  • RNA, Messenger
  • Adrenocorticotropic Hormone
  • Cytochrome P-450 Enzyme System
  • Cyclic AMP
  • Hydrocortisone
  • Epinephrine