ROLE OF GPER IN THE ANTERIOR PITUITARY GLAND FOCUSING ON LACTOTROPH FUNCTION

CAMILLETTI, MARÍA ANDREA; PEREZ, PABLO; GUTIERREZ, SILVINA; ABELEDO-MACHADO, ALEJANDRA; FARAONI, ERIKA YANIL; DÍAZ -TORGA GRACIELA; FERRARIS, JIMENA; PISERA, DANIEL; CAMILLETTI, MARÍA ANDREA; PEREZ, PABLO; GUTIERREZ, SILVINA; ABELEDO-MACHADO, ALEJANDRA; FARAONI, ERIKA YANIL; DÍAZ -TORGA GRACIELA; FERRARIS, JIMENA; PISERA, DANIEL

Mar del PLata

Congreso; Sociedad Argentina de Investigación Clínica; 2018

SAIC

Ovarian steroids control a variety of physiological functions. They exert actions through classical nuclear steroid receptors, but rapid non-genomic actions through specific membrane steroid receptors have been also described. In this study, we demonstrate that the G-protein-coupled estrogen receptor (GPER) is expressed in the rat pituitary gland 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 are GPER-positive (flow cytomety). By immunohistochemical and inmuno-electron-microscopy studies we demonstrated that GPER is localized in the plasmatic membrane but is also associated to the endoplasmic reticulum in rat lactotrophs. Moreover, we found that local Gper expression is regulated by 17β-estradiol (E2) and progesterone (P4) since in vivo treatments with E2 and P4 both negatively regulated pituitary Gper expression in female rats. Accordingly, Gper mRNA levels were differentially modulated during the estrous cycle. Due to the loss of the control by ovarian steroids, Gper expression was significantly increased in the pituitary gland of ovariectomized (OVX) adult female rats. Interestingly, GPER protein levels were found increased specifically in pituitary lactotrophs of OVX rats. The role of GPER in the lactotroph population is unknown. Our results demonstrate a rapid estradiol stimulatory effect on PRL secretion mediated by GPER, both in vitro and ex vivo, using a GPER agonist G1. This effect was prevented by the GPER antagonist G36, demonstrating a novel role for this receptor in the lactotroph population. Taken together, this data provides the first evidence that GPER is highly expressed in lactotroph population, is regulated by ovarian steroids, and its pituitary expression increases after OVX. These changes could lead to alterations in the pituitary function and therefore should be taken into consideration in the response of the gland to an eventual hormone replacement therapy.