The crucial role of glucocorticoids in obesity and insulin resistance and the actions of the OB protein leptin on the hypothalamic-pituitary-adrenal (HPA) axis suggest that there is an important interaction of leptin with the glucocorticoid system. Therefore, we designed a study to test the effect of leptin directly on adrenocortical steroidogenesis. Primary cultures of bovine adrenocortical cells were incubated with increasing concentrations (10–1,000 ng/ml) of recombinant mouse leptin for 24 h, and the effects of leptin on basal and ACTH-stimulated cortisol secretion were determined. The accumulation of P450 17α mRNA following incubation with ACTH (10 nmol/1) and leptin (10–1,000 ng/ml) was analyzed by Northern blot. Adrenocortical cells were characterized by immunohistochemical staining for 17α-hydroxyprogesterone. Leptin (10–1,000 ng/ml) inhibited basal and ACTHstimulated cortisol release. At a concentration that occurs in obese individuals in vivo (100 ng/ml), it reduced basal cortisol secretion to 52.7 ± 37% (mean ± SE). The rise in cortisol secretion following maximal ACTH stimulation (10 nmol/1) was blunted to 55.2 ± 27%. At more physiological concentrations of ACTH (0.1 nmol/1), the inhibition of cortisol release by coincubation with low doses of leptin (10 ng/ml) was even more pronounced, leading to a reduction to 32.8% (1,248 ± 134 vs. 410 ± 157 nmol/1). Addition of OB protein (10–1,000 ng/ml) led to a dose-dependent reduction of ACTH-stimulated cytochrome P450 17α mRNA accumulation (from 80 to 45%), suggesting that leptin regulates adrenal steroidogenesis at the transcriptional level. These data clearly demonstrate that leptin inhibits cortisol production in adrenocortical cells and therefore appears to be a metabolic signal that directly acts on the adrenal gland.
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July 01 1997
Evidence for a Novel Peripheral Action of Leptin as a Metabolic Signal to the Adrenal Gland: Leptin Inhibits Cortisol Release Directly Free
Stefan R Bornstein;
Stefan R Bornstein
Department of Internal Medicine III, University of Leipzig
Leipzig
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Katja Uhlmann;
Katja Uhlmann
Department of Internal Medicine III, University of Leipzig
Leipzig
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Andrea Haidan;
Andrea Haidan
Department of Internal Medicine III, University of Leipzig
Leipzig
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Monika Ehrhart-Bornstein;
Monika Ehrhart-Bornstein
Department of Internal Medicine III, University of Leipzig
Leipzig
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Werner A Scherbaum
Werner A Scherbaum
Diabetes Research Institute at the University of Diisseldorf
Diisseldorf, Germany
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Address correspondence and reprint requests to Dr. Stefan R. Bornstein, Department of Internal Medicine III, University of Leipzig, Phillip-Rosenthal-Str. 27, 04103 Leipzig, Germany.
1
CRH, corticotropin-releasing hormone; HPA, hypothalamic-pituitaryadrenal; NPY, neuropeptide Y.
Diabetes 1997;46(7):1235–1238
Article history
Received:
March 24 1997
Revision Received:
April 30 1997
Accepted:
April 30 1997
PubMed:
9200662
Citation
Stefan R Bornstein, Katja Uhlmann, Andrea Haidan, Monika Ehrhart-Bornstein, Werner A Scherbaum; Evidence for a Novel Peripheral Action of Leptin as a Metabolic Signal to the Adrenal Gland: Leptin Inhibits Cortisol Release Directly. Diabetes 1 July 1997; 46 (7): 1235–1238. https://doi.org/10.2337/diab.46.7.1235
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