Chonnam Med J.  2005 Dec;41(3):237-242.

Effects of Nitric Oxide on Cytochrome P450SCC Activity in Adrenal Cortical Cells

• Jung K
• Kang CG
• Choi IS
• Lee KY

Abstract

Nitric oxide (NO) modulates steroid hormone synthesis. However, the precise mechanism of the inhibitory action of NO on the hormone synthesis is not well clarified. Synthesis of pregnenolone from cholesterol by cytochrome P450 side chain cleavage enzyme (P450scc) is the first step and the regulatory site of steroid hormone synthesis. We checked the effects of NO on P450scc activity by 14C-pregnenolone synthesis from 14C-cholesterol in rat adrenal cortical cells. Sodium nitroprusside (SNP), a NO donor, inhibited pregnenolone synthesis in a dose-dependent manner, the IC50 being 70microM. Dibutyryl-cGMP (1 mM) also inhibited the pregnenolone synthesis by 15%. Guanylate cyclase activity of the adrenal cortical cells was increased by SNP dose-dependently. These data show that NO inhibits steroid hormone synthesis by both inhibition of P450scc and guanylate cyclase.

Keyword

NO; Cytochrome P450; Guanylate cyclase; Adrenocortical cells

MeSH Terms

Animals
Cholesterol
Cholesterol Side-Chain Cleavage Enzyme*
Cytochrome P-450 Enzyme System
Cytochromes*
Guanylate Cyclase
Humans
Inhibitory Concentration 50
Nitric Oxide*
Nitroprusside
Pregnenolone
Rats
Tissue Donors
Cholesterol
Cholesterol Side-Chain Cleavage Enzyme
Cytochrome P-450 Enzyme System
Cytochromes
Guanylate Cyclase
Nitric Oxide
Nitroprusside
Pregnenolone