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

Deborah J. Clegg, Lynda M. Brown, Jeffrey M. Zigman, Christopher J. Kemp, April D. Strader, Stephen C. Benoit, Stephen C. Woods, Michela Mangiaracina, Nori Geary

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Abstract

Ghrelin, the only known orexigenic gut hormone, is secreted mainly from the stomach, increases with fasting and before meal initiation in humans and rats, and increases food intake after central or peripheral administration. To investigate sex differences in the action of ghrelin, we assessed the effects of exogenous ghrelin in intact male and female rats, the effects of exogenous ghrelin in ovariectomized (OVX) and estradiol (E2)-treated female rats, as well as the effects of OVX on plasma ghrelin and hypothalamic orexigneic neuropeptide expression in rats and on food intake and weight gain in transgenic mice lacking the ghrelin receptor (Ghsr-/- mice). Male and OVX female rats were significantly more sensitive than intact female rats to the orexigenic effects of both centrally (intra-third ventricular, i3vt, 0.01, 0.1, and 1.0 nmol) and systemically (ip, 3, 6, and 9 nmol) administered ghrelin. This difference is likely to be estradiol dependent because E2 attenuated the orexigenic action of ghrelin in OVX female and male rats. Furthermore, OVX increased food intake and body weight in wild-type mice, but not in Ghsr -/- mice, suggesting that OVX increases food intake by releasing ghrelin from a tonic inhibitory effect of estradiol. In addition, following OVX, there was an increase in plasma ghrelin that was temporally associated with increased food intake, body weight, and hypothalamic neuropeptide Y and Agoutirelated protein mRNA expression. Collectively, these data suggest that estradiol inhibits the orexigenic action of ghrelin in females, that weight gain associated with OVX is ghrelin mediated, and that this endocrine interaction may account for an important sex differences in food intake and the regulation of body weight.

Original languageEnglish (US)
Pages (from-to)1051-1058
Number of pages8
JournalDiabetes
Volume56
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

Ghrelin
Estradiol
Eating
Body Weight
Sex Characteristics
Weight Gain
Ghrelin Receptor
Appetite Regulation
Neuropeptide Y
Neuropeptides
Transgenic Mice
Meals
Fasting
Stomach
Hormones

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Clegg, D. J., Brown, L. M., Zigman, J. M., Kemp, C. J., Strader, A. D., Benoit, S. C., ... Geary, N. (2007). Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats. Diabetes, 56(4), 1051-1058. https://doi.org/10.2337/db06-0015

Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats. / Clegg, Deborah J.; Brown, Lynda M.; Zigman, Jeffrey M.; Kemp, Christopher J.; Strader, April D.; Benoit, Stephen C.; Woods, Stephen C.; Mangiaracina, Michela; Geary, Nori.

In: Diabetes, Vol. 56, No. 4, 04.2007, p. 1051-1058.

Research output: Contribution to journalArticle

Clegg, DJ, Brown, LM, Zigman, JM, Kemp, CJ, Strader, AD, Benoit, SC, Woods, SC, Mangiaracina, M & Geary, N 2007, 'Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats', Diabetes, vol. 56, no. 4, pp. 1051-1058. https://doi.org/10.2337/db06-0015
Clegg DJ, Brown LM, Zigman JM, Kemp CJ, Strader AD, Benoit SC et al. Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats. Diabetes. 2007 Apr;56(4):1051-1058. https://doi.org/10.2337/db06-0015
Clegg, Deborah J. ; Brown, Lynda M. ; Zigman, Jeffrey M. ; Kemp, Christopher J. ; Strader, April D. ; Benoit, Stephen C. ; Woods, Stephen C. ; Mangiaracina, Michela ; Geary, Nori. / Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats. In: Diabetes. 2007 ; Vol. 56, No. 4. pp. 1051-1058.
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abstract = "Ghrelin, the only known orexigenic gut hormone, is secreted mainly from the stomach, increases with fasting and before meal initiation in humans and rats, and increases food intake after central or peripheral administration. To investigate sex differences in the action of ghrelin, we assessed the effects of exogenous ghrelin in intact male and female rats, the effects of exogenous ghrelin in ovariectomized (OVX) and estradiol (E2)-treated female rats, as well as the effects of OVX on plasma ghrelin and hypothalamic orexigneic neuropeptide expression in rats and on food intake and weight gain in transgenic mice lacking the ghrelin receptor (Ghsr-/- mice). Male and OVX female rats were significantly more sensitive than intact female rats to the orexigenic effects of both centrally (intra-third ventricular, i3vt, 0.01, 0.1, and 1.0 nmol) and systemically (ip, 3, 6, and 9 nmol) administered ghrelin. This difference is likely to be estradiol dependent because E2 attenuated the orexigenic action of ghrelin in OVX female and male rats. Furthermore, OVX increased food intake and body weight in wild-type mice, but not in Ghsr -/- mice, suggesting that OVX increases food intake by releasing ghrelin from a tonic inhibitory effect of estradiol. In addition, following OVX, there was an increase in plasma ghrelin that was temporally associated with increased food intake, body weight, and hypothalamic neuropeptide Y and Agoutirelated protein mRNA expression. Collectively, these data suggest that estradiol inhibits the orexigenic action of ghrelin in females, that weight gain associated with OVX is ghrelin mediated, and that this endocrine interaction may account for an important sex differences in food intake and the regulation of body weight.",
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