Regulation of Glucose Transporter 1 (Slc2a1) in the Pituitary Gonadotrope of Mice after Puberty

Francina Gonzalez De Los Santos

doi:10.4172/2157-7536.1000138

Abstract

Glucose provides fuel for cell metabolism and plays an important role in normal reproductive function. Glucose transporters such as (SLC2A1) facilitate entry of glucose into cells. We have previously shown that gonadotropin releasing hormone (GnRH) stimulates Slc2a1 expression in Li¢T2 gonadotrope cells and in the pituitary gland of pre-pubertal mice. In this study we examined changes in Slc2a1 expression in the pituitary gland of mice after puberty and in Li¢T2 gonadotrope cells treated with sex steroids. There were no detectable changes in Slc2a1 gene expression in the pituitary gland of pre-pubertal and adult male and female mice using real-time PCR analysis. In contrast, Western blot analysis detected higher levels of SLC2A1 protein in the pituitary gland of adult male and female mice compared to pre-pubertal male and female mice, respectively. In addition, peak levels of SLC2A1 protein as determined by Western blot analysis were detected in the pituitary gland of female mice during the proestrus and oestrus stages of the oestrous cycle. The proestrus stage corresponds to the surge of luteinizing hormone in the gonadotrope, which then triggers ovulation. Additional studies using immunofluorescent analysis of pituitary glands revealed increased co-localization of SLC2A1 with luteinizing hormone i¢(LHi¢)i in the gonadotrope cell of adult male and female mice compared to pre-pubertal mice. In vitro studies in Li¢T2 cells did not detect any effects of estradiol and/or progesterone on Slc2a1 expression by real-time PCR analysis, but estradiol alone increased SLC2A1 protein levels in Li¢T2 cells as determined by Western blot analysis. Furthermore, combined treatment of estradiol and progesterone induced glucose uptake in Li¢T2 cells. Together, our findings show that regulation of Slc2a1 in the gonadotrope of adult mice likely reflects changes in sex steroids that are also important for pubertal development and fertility.

Highlights

Pubertal development and normal reproductive function are regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which consists of gonadotropin releasing hormone (GnRH) neurons, the pituitary gonadotrope cells, and the gonad [1,2,3]
We showed that treatment of pre-pubertal mice with exogenous GnRH increased Slc2a1 mRNA expression but not Slc2a2, Slc2a4, or Slc2a8 in the mouse pituitary gland, which suggests that Slc2a1 may be important for glucose metabolism in the gonadotrope compared to other glucose transporters
SLC2A1 protein regulation in the murine pituitary gland Since changes in Slc2a1 mRNA levels were not detected in the pituitary glands of male and female mice, we investigated if there is regulation of SLC2A1 protein in the pituitary gland of mice

Summary

Introduction

Pubertal development and normal reproductive function are regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which consists of gonadotropin releasing hormone (GnRH) neurons, the pituitary gonadotrope cells, and the gonad [1,2,3]. The hypothalamus contains specialized neurons that secrete GnRH, which binds to its receptor located on the gonadotrope cell in the anterior pituitary gland to stimulate the synthesis and secretion of the gonadotropins; luteinizing hormone (LH) and follicle stimulating hormone (FSH). Progesterone and testosterone are the main sex steroids produced by the gonads, and these steroids regulate the HPG axis through negative feedback inhibition at the level of the hypothalamic GnRH neuron and the pituitary gonadotrope cells [3,4,5]. Regulation of HPG axis by GnRH and sex steroids is important for puberty and fertility

Methods

Results

Conclusion