Dose-dependent cortisol-induced increases in plasma leptin concentration in healthy humans

John W. Newcomer, Gregg Selke, Angela Kelly Melson, John Gross, George P. Vogler, Samuel Dagogo-Jack

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Background: Leptin is a hormone that regulates fat metabolism and appetite. The secretion of leptin is regulated by adiposity and, in the rodent, by factors such as insulin, β-adrenergic agonists, and glucocorticoids (GCs). Increased secretion o[ the endogenous human GC, cortisol, occurs during stress and in disorders such as major depression. Pharmacological GCs can robustly increase plasma leptin concentrations in humans, leading us to hypothesize that cortisol may serve as a physiological regulator of human leptin secretion. Methods: A randomized double-blind placebo-controlled comparison of 2 fixed oral dosages o[ cortisol (40 mg/d and 160 mg/d), given for 4 days to matched groups of healthy subjects (n = 47). Low-dose treatment approximated GC output during mild stress, while high-dose treatment approximated GC output during maximal stress, spanning a range of GC secretion relevant to physiological stress. Results: Cortisol produced dose-dependent and time-dependent increases in plasma leptin concentrations (time X treatment condition X body mass index; F6,123= 10.73; P<.001). Initial treatment-induced increases in plasma leptin concentration returned toward baseline values during 4 treatment days, suggesting tolerance to this GC effect in these healthy subjects. Conclusions: The results indicate an important role for GCs in the short- term regulation of human leptin secretion. Glucocorticoid-induced increases in leptin secretion suggest a mechanism that may contribute to anorexia and weight loss during stress and disease states such as major depression, if these conditions are associated with sustained increases in plasma leptin concentrations.

Original languageEnglish (US)
Pages (from-to)995-1000
Number of pages6
JournalArchives of General Psychiatry
Volume55
Issue number11
DOIs
StatePublished - Nov 17 1998

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Leptin
Glucocorticoids
Hydrocortisone
Healthy Volunteers
Depression
Therapeutics
Plasma
Dose
Cortisol
Secretion
Adrenergic Agonists
Physiological Stress
Adiposity
Anorexia
Appetite
Weight Loss
Rodentia
Body Mass Index
Research Design
Fats

All Science Journal Classification (ASJC) codes

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

Cite this

Dose-dependent cortisol-induced increases in plasma leptin concentration in healthy humans. / Newcomer, John W.; Selke, Gregg; Melson, Angela Kelly; Gross, John; Vogler, George P.; Dagogo-Jack, Samuel.

In: Archives of General Psychiatry, Vol. 55, No. 11, 17.11.1998, p. 995-1000.

Research output: Contribution to journalArticle

Newcomer, John W. ; Selke, Gregg ; Melson, Angela Kelly ; Gross, John ; Vogler, George P. ; Dagogo-Jack, Samuel. / Dose-dependent cortisol-induced increases in plasma leptin concentration in healthy humans. In: Archives of General Psychiatry. 1998 ; Vol. 55, No. 11. pp. 995-1000.
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