Role of GPER in the anterior pituitary gland focusing on lactotroph function

Abstract

Ovarian steroids control a variety of physiological functions. They exert actions throughclassical nuclear steroid receptors, but rapid non-genomic actions through specificmembrane steroid receptors have been also described. In this study, we demonstratethat the G-protein-coupled estrogen receptor (GPER) is expressed in the rat pituitarygland and, at a high level, in the lactotroph population. Our results revealed that~40% of the anterior pituitary cells are GPER positive and ~35% of the lactotrophs areGPER positive. By immunocytochemical and immuno-electron-microscopy studies, wedemonstrated that GPER is localized in the plasmatic membrane but is also associatedto the endoplasmic reticulum in rat lactotrophs. Moreover, we found that local Gperexpression is regulated negatively by 17β-estradiol (E2) and progesterone (P4) andfluctuates during the estrus cycle, being minimal in proestrus. Interestingly, lack ofovarian steroids after an ovariectomy (OVX) significantly increased pituitary GPERexpression specifically in the three morphologically different subtypes of lactotrophs.We found a rapid estradiol stimulatory effect on PRL secretion mediated by GPER,both in vitro and ex vivo, using a GPER agonist G1, and this effect was prevented by theGPER antagonist G36, demonstrating a novel role for this receptor. Then, the increasedpituitary GPER expression after OVX could lead to alterations in the pituitary functionas all three lactotroph subtypes are target of GPER ligand and could be involved in thePRL secretion mediated by GPER. Therefore, it should be taken into consideration in theresponse of the gland to an eventual hormone replacement therapy