Leptin Inhibits Directly Glucocorticoid Secretion by Normal Human and Rat Adrenal Gland**This work was supported by a grant from the Swiss National Science Foundation (No. 3100–050748.97/1).
Abstract
Different interactions have been described between glucocorticoids and the product of the ob gene leptin. Leptin can inhibit the activation of the hypothalamo-pituitary-adrenal axis by stressful stimuli, whereas adrenal glucocorticoids stimulate leptin production by the adipocyte. The present study was designed to investigate the potential direct effects of leptin to modulate glucocorticoid production by the adrenal. Human adrenal glands from kidney transplant donors were dissociated, and isolated primary cells were studied in vitro. These cells were preincubated with recombinant leptin (10(-10)-10(-7) M) for 6 or 24 h, and basal or ACTH-stimulated cortisol secretion was subsequently measured. Basal cortisol secretion was unaffected by leptin, but a significant and dose-dependent inhibition of ACTH-stimulated cortisol secretion was observed [down by 29 +/- 0.1% of controls with the highest leptin dose, P < 0.01 vs. CT (unrelated positive control)]. This effect of leptin was also observed in rat primary adrenocortical cells, where leptin inhibited stimulated corticosterone secretion in a dose-dependent manner (down by 46 +/- 0.1% of controls with the highest leptin dose, P < 0.001 vs. CT). These effects of leptin in adrenal cells are likely mediated by the long isoform of the leptin receptor (OB-R), because its transcript was found to be expressed in the adrenal tissue and leptin had no inhibitory effect in adrenal glands obtained from db/db mice. Therefore, leptin inhibits directly stimulated cortisol secretion from human and rat adrenal glands, and this may represent an important mechanism to modulate glucocorticoid levels in various metabolic states.
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Cortisol increases or stimulates production of leptin in adipose tissue.
“Cortisol increases or stimulates production of leptin in adipose tissue (44).”
From Sparse System Identification of Leptin Dynamics in Women With Obesity (2022) · cites this paper as [44]
Leptin inhibits the HPA axis, which via neuroendocrine hormones like ACTH results in a reduction in cortisol.
“leptin inhibits the HPA axis, which, via neuroendocrine hormones like ACTH, results in a reduction in cortisol (43, 44).”
From Sparse System Identification of Leptin Dynamics in Women With Obesity (2022) · cites this paper as [44]
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- Authors
- Pralong, F. P., Roduit, R., Waeber, G., Castillo, E., Mosimann, F., Thorens, B., & Gaillard, R. C.
- Affiliations
- Division of Endocrinology, Diabetology and Metabolism (F.P.P., E.C., R.C.G.), University Hospital, 1011 Lausanne, Switzerland
- Institute of Pharmacology and Toxicology (R.R., B.T.), University Hospital, 1011 Lausanne, Switzerland
- Service of Internal Medicine B (G.W.) University Hospital, 1011 Lausanne, Switzerland
- Centre Hospitalier Universitaire Vaudois (CH)
- Department of Surgery (F.M.), University Hospital, 1011 Lausanne, Switzerland
- ORCID
- Thorens, Bernard
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1998-10-01
- Volume
- 139
- Issue
- 10
- Pages
- 4264-4268
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2050930379
- Cited by
- 202
- References
- 40
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 6 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 2 · 2015: 2 · 2014: 11 · 2013: 5 · 2012: 7
- FWCI
- 6.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- leptin, glucocorticoid secretion, adrenal cortex, cortisol, ACTH stimulation test, corticosterone, adrenocortical cells, leptin receptor, hypothalamic-pituitary-adrenal axis, db/db mice, adipokines
- MeSH terms
- Adrenal Glands, Adrenocorticotropic Hormone, Animals, Corticosterone, Dose-Response Relationship, Drug, Female, Humans, Hydrocortisone, Proteins, Rats, Wistar, Leptin, Rats
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