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 17alpha-hydroxylase cytochrome P450 mRNA expression. To analyze if leptin regulates other major enzymes involved in adrenal steroidogenesis we tested its effect on mRNA expression for two further key enzymes, C21-hydroxylase (P450C21) and side-chain cleavage enzyme (P450SCC). Cultured bovine cortical cells were stimulated for 24 hours with 10 nM ACTH, with 10 nM ACTH plus 100 ng/ml leptin or left unstimulated 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 unstimulated controls. Addition of leptin led to a reduction of ACTH-stimulated mRNA accumulation of 73% for P450C21 and of 45% for P450SCC. We therefore suggest that leptin reduces cortisol synthesis in the adrenal by down-regulating the steroid producing enzyme cascade in the cortical cell.
Kruse
M
M
Diabetes Research Institute at the University of Duesseldorf, Clinical Department, Germany.
Bornstein
S R
SR
Uhlmann
K
K
Paeth
G
G
Scherbaum
W A
WA
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D020738:Leptin; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000235:genetics
D000305:Adrenal Cortex Hormones; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D013255:Steroid 21-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme