This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cherradi, N. Articles by Pralong, F. P. Search for Related Content PubMed PubMed Citation Articles by Cherradi, N. Articles by Pralong, F. P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Steroids

Decreased Expression of Steroidogenic Acute Regulatory Protein: A Novel Mechanism Participating in the Leptin-Induced Inhibition of Glucocorticoid Biosynthesis

Division of Endocrinology, Diabetology and Metabolism, University of Lausanne Medical School (R.C.G., F.P.P.), CH-1011 Lausanne, Switzerland; and Division of Endocrinology and Diabetology, University of Geneva Medical School (N.C., A.M.C.), CH-1211 Geneva 14, Switzerland

Address all correspondence and requests for reprints to: François P. Pralong, M.D., BH 19-707, University of Lausanne Medical School, CH-1011 Lausanne, Switzerland. E-mail: francois.pralong{at}chuv.hospvd.ch

The adipocyte-derived hormone leptin is a central modulator of food intake, metabolism and neuroendocrine functions. It is also involved in a physiological loop linking the activity of the hypothalamo-pituitary-adrenal axis and adipose tissue. At the adrenal level, leptin has been shown to antagonize the effects of ACTH on glucocorticoid biosynthesis by decreasing the expression of various enzymes of the steroid biosynthetic pathway. The steroidogenic acute regulatory protein regulates cholesterol delivery to the P450_scc enzyme, a process that is rate limiting in steroid hormone biosynthesis. We have demonstrated here that leptin significantly inhibits the expression of steroidogenic acute regulatory protein in primary cultures of rat adrenocortical cells. This inhibition was observed at both the protein and mRNA levels. In contrast, leptin was not found to interfere with the expression of the cytosolic enzyme cholesterol ester hydrolase or with that of the mitochondrial enzyme P450_scc. In addition, we observed the anticipated stimulation of cAMP production by ACTH in the presence of leptin, suggesting that it does not interfere with intracellular ACTH signaling. In summary, our data provide evidence that the interplay existing between leptin and ACTH in vivo is mediated at least partially via a direct and opposite modulation of steroidogenic acute regulatory protein, a key factor in the adrenal steroid biosynthetic pathway. This effect of leptin could also be relevant to other steroidogenic tissues.

This article has been cited by other articles:

				H.-T. Hsu, Y.-C. Chang, Y.-N. Chiu, C.-L. Liu, K.-J. Chang, and I.-C. Guo Leptin Interferes with Adrenocorticotropin/3',5'-Cyclic Adenosine Monophosphate (cAMP) Signaling, Possibly through a Janus Kinase 2-Phosphatidylinositol 3-Kinase/Akt-Phosphodiesterase 3-cAMP Pathway, to Down-Regulate Cholesterol Side-Chain Cleavage Cytochrome P450 Enzyme in Human Adrenocortical NCI-H295 Cell Line J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2761 - 2769. [Abstract] [Full Text] [PDF]

				A. Martin, R. de Vittoris, V. David, R. Moraes, M. Begeot, M.-H. Lafage-Proust, C. Alexandre, L. Vico, and T. Thomas Leptin Modulates both Resorption and Formation while Preventing Disuse-Induced Bone Loss in Tail-Suspended Female Rats Endocrinology, August 1, 2005; 146(8): 3652 - 3659. [Abstract] [Full Text] [PDF]

				B.S.J. Yuen, P.C. Owens, M.E. Symonds, D.H. Keisler, J.R. McFarlane, K.G. Kauter, and I.C. McMillen Effects of Leptin on Fetal Plasma Adrenocorticotropic Hormone and Cortisol Concentrations and the Timing of Parturition in the Sheep Biol Reprod, June 1, 2004; 70(6): 1650 - 1657. [Abstract] [Full Text] [PDF]

				C. Salzmann, M. Otis, H. Long, C. Roberge, N. Gallo-Payet, and C.-D. Walker Inhibition of Steroidogenic Response to Adrenocorticotropin by Leptin: Implications for the Adrenal Response to Maternal Separation in Neonatal Rats Endocrinology, April 1, 2004; 145(4): 1810 - 1822. [Abstract] [Full Text] [PDF]

				E. Charmandari, M. Weise, S. R. Bornstein, G. Eisenhofer, M. F. Keil, G. P. Chrousos, and D. P. Merke Children with Classic Congenital Adrenal Hyperplasia Have Elevated Serum Leptin Concentrations and Insulin Resistance: Potential Clinical Implications J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2114 - 2120. [Abstract] [Full Text] [PDF]

				G. E. Bergonzelli, F. P. Pralong, M. Glauser, C. Cavadas, E. Grouzmann, and R. C. Gaillard Interplay Between Galanin and Leptin in the Hypothalamic Control of Feeding via Corticotropin-Releasing Hormone and Neuropeptide Y Diabetes, December 1, 2001; 50(12): 2666 - 2672. [Abstract] [Full Text] [PDF]