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

First Author  Brothers KJ Year  2010
Journal  Cell Metab Volume  12
Issue  3 Pages  295-305
PubMed ID  20816095 Mgi Jnum  J:166365
Mgi Id  MGI:4844199 Doi  10.1016/j.cmet.2010.06.010
Citation  Brothers KJ, et al. (2010) Rescue of obesity-induced infertility in female mice due to a pituitary-specific knockout of the insulin receptor. Cell Metab 12(3):295-305
abstractText  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.
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