Leptin down-regulates the steroid producing system in the adrenal

OB protein leptin inhibits the secretion of cortisol in primary cultures of bovine adrenocortical cells and down-regulates 17 alpha-hydroxylase cytoch rome P450 mRNA expression. To analyze if leptin regulates other major enzym es involved in adrenal steroidogenesis we tested its effect on mRNA express ion for two further key enzymes, C21-hydroxylase (P450C21) and side-chain c leavage enzyme (P450SCC). Cultured bovine cortical cells were stimulated fo r 24 hours with 10 nM ACTH, with 10 nM ACTH plus 100 ng/ml leptin or left u nstimulated as controls. Stimulation with ACTH led to a 1.75-fold increase of P450C21 mRNA and a 3.31-fold increase of P450SCC mRNA compared to unstim ulated controls. Addition of leptin led to a reduction of ACTH-stimulated m RNA accumulation of 73% for P450C21 and of 45% for P450SCC. We therefore su ggest that leptin reduces cortisol synthesis in the adrenal by down-regulat ing the steroid producing enzyme cascade in the cortical cell.