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Cell Metab. 2010 Sep 8;12(3):295-305. doi: 10.1016/j.cmet.2010.06.010.

Rescue of obesity-induced infertility in female mice due to a pituitary-specific knockout of the insulin receptor.

Author information

1
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

Abstract

Obesity is associated with insulin resistance in metabolic tissues such as adipose, liver, and muscle, but it is unclear whether nonclassical target tissues, such as those of the reproductive axis, are also insulin resistant. To determine if the reproductive axis maintains insulin sensitivity in obesity in vivo, murine models of diet-induced obesity (DIO) with and without intact insulin signaling in pituitary gonadotrophs were created. Diet-induced obese wild-type female mice (WT DIO) were infertile and experienced a robust increase in luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) or insulin stimulation. By contrast, both lean and obese mice with a pituitary-specific knockout of the insulin receptor (PitIRKO) exhibited reproductive competency, indicating that insulin signaling in the pituitary is required for the reproductive impairment seen in DIO and that the gonadotroph maintains insulin sensitivity in a setting of peripheral insulin resistance.

PMID:
20816095
PMCID:
PMC2935812
DOI:
10.1016/j.cmet.2010.06.010
[Indexed for MEDLINE]
Free PMC Article

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