Estrogen receptor beta expression fluctuates during the estrous cycle contributing to the balance of the pituitary cell proliferation

PEREZ P.; PETITI J.P.; WAGNER I. A.; SABATINO M. E.; DE PAUL A.L.; TORRES A. I.; GUTIÉRREZ S.

Congreso; 16 congress of Spanish Society of Neuroscience; 2015

17β-estradiol (E2) levels fluctuate during the estrous cycle regulating pituitary cell proliferation through its specific estrogen receptors (ER) a and b. Although an important number of studies have demonstrated the function of ERa in pituitary cell proliferation, the role of ERb in the growth of pituitary cells is not well known. This background leads us to study the expression of ERb during the estrous cycle and analyze if this subtype of ER modulates the expression of cell cycle regulators.Pituitary glands from female Wistar rats at different stages of the estrous cycle (proestrus, estrus and diestrus) and GH3 cells transfected to over-expression of ERb (GH3b+) were used. E2 and the agonists of ERa (PPT) and ERb (DPN) were employed. ERa and b expression was quantified by flow cytometry, cyclin D1 and CDK4 expression was detected by Western Blot and the GH3 proliferation was analyzed by BrdU technique. The statistical analysis used was ANOVA-Tukey. 34.12 ± 7.7 % of pituitary cells obtained from rats in diestrus expressed ERb, 35.4 ± 2.5 % were ERb+ in the proestrus, with a decrease in the ERb expression in estrus, with an 18.79 ± 1.1% of ERb+. However, ERa levels were similar during the estrous cycle. In pituitary cells from rats in proestrus and estrus the cyclin D1 levels were increased in relation to those found in diestrus. Over-expression of ERb in GH3 cells decreased the pituitary cell proliferation and the cyclin D1 level expression.These results indicate that ERb levels in the pituitary gland fluctuate during the estrous cycle and suggest that its expression is modulated by E2. The ERb exerts an inhibitory role on the anterior pituitary cell proliferation with participation of the cyclin D1, adjusting the cell population and its functionality to the body´s requirements.