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Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats.

Deborah J Clegg1, Lynda M Brown, Jeffrey M Zigman

  • 1Department of Psychiatry, University of Cincinnati, P.O. Box 670559, Cincinnati, OH 45267-0559, USA. debbie.clegg@uc.edu

Diabetes
|January 26, 2007
PubMed
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Estradiol inhibits the appetite-stimulating hormone ghrelin in female rats. Ovariectomy-induced weight gain is ghrelin-dependent, highlighting sex differences in appetite regulation.

Area of Science:

  • Endocrinology
  • Neuroscience
  • Reproductive Biology

Background:

  • Ghrelin, an orexigenic gut hormone, stimulates food intake.
  • Sex differences in appetite and body weight regulation are well-documented.
  • Estradiol's role in modulating ghrelin's effects is not fully understood.

Purpose of the Study:

  • To investigate sex differences in the orexigenic action of ghrelin.
  • To determine the influence of estradiol on ghrelin's effects.
  • To elucidate the mechanisms underlying ovariectomy-induced weight gain.

Main Methods:

  • Administered exogenous ghrelin to intact and ovariectomized (OVX) male and female rats.
  • Assessed the effects of estradiol (E2) treatment in OVX rats.
  • Examined plasma ghrelin levels, hypothalamic neuropeptide expression, and food intake in wild-type and ghrelin receptor knockout (Ghsr(-/-)) mice after OVX.

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Main Results:

  • Male and OVX female rats showed increased sensitivity to ghrelin's orexigenic effects compared to intact females.
  • Estradiol treatment attenuated ghrelin's action in OVX female and male rats.
  • OVX increased food intake and body weight in wild-type mice but not in Ghsr(-/-) mice, accompanied by elevated plasma ghrelin and hypothalamic orexigenic neuropeptide mRNA.

Conclusions:

  • Estradiol exerts an inhibitory effect on ghrelin's orexigenic action in females.
  • Weight gain following OVX is mediated by ghrelin signaling.
  • These findings reveal a critical endocrine interaction contributing to sex differences in appetite and body weight regulation.