Insulin receptor signaling in the GnRH neuron plays a role in the abnormal GnRH pulsatility of obese female mice

PloS One
Sara A DivallAndrew Wolfe

Abstract

Infertility associated with obesity is characterized by abnormal hormone release from reproductive tissues in the hypothalamus, pituitary, and ovary. These tissues maintain insulin sensitivity upon peripheral insulin resistance. Insulin receptor signaling may play a role in the dysregulation of gonadotropin-releasing hormone (GnRH) secretion in obesity, but the interdependence of hormone secretion in the reproductive axis and the multi-hormone and tissue dysfunction in obesity hinders investigations of putative contributing factors to the disrupted GnRH secretion. To determine the role of GnRH insulin receptor signaling in the dysregulation of GnRH secretion in obesity, we created murine models of diet-induced obesity (DIO) with and without intact insulin signaling in the GnRH neuron. Obese control female mice were infertile with higher luteinizing hormone levels and higher GnRH pulse amplitude and total pulsatile secretion compared to lean control mice. In contrast, DIO mice with a GnRH specific knockout of insulin receptor had improved fertility, luteinizing hormone levels approaching lean mice, and GnRH pulse amplitude and total secretion similar to lean mice. Pituitary responsiveness was similar between genotypes. These res...Continue Reading

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Citations

Dec 31, 2015·Human Reproduction Update·Roberto MaggiPatrizia Limonta
Dec 23, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Laverne Camille Melón, Jamie Maguire
Oct 21, 2015·Journal of Neuroendocrinology·Maggie C EvansGreg M Anderson
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Oct 18, 2019·Frontiers in Endocrinology·Anastasia DimakopoulouWaljit S Dhillo
Jun 7, 2017·Endocrinology·Natalie M Hohos, Malgorzata E Skaznik-Wikiel
Sep 13, 2019·Endocrinology·Nancy M Lainez, Djurdjica Coss
Feb 2, 2021·Journal of Neuroendocrinology·Maggie C EvansGreg M Anderson
Aug 5, 2020·Molecular and Cellular Endocrinology·Emma K McIlwraith, Denise D Belsham

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Methods Mentioned

BETA
genotyping
sedation
Assay
PCR

Software Mentioned

GraphPad4
AxioVision

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