INSTITUTO DE INVESTIGACIONES EN CIENCIAS DE LA SALUD
Unidad Ejecutora - UE
Inhibitory role of ERb on anterior pituitary cell proliferation by controlling the expression of proteins related to cell cycle progression
PEREZ P.; PETITI J.P.; WAGNER I. A.; SABATINO M. E.; SASSO C. V.; DE PAUL A.L.; TORRES A.I.; GUTIÉRREZ S.
MOLECULAR AND CELLULAR ENDOCRINOLOGY.
ELSEVIER IRELAND LTD
Lugar: Amsterdam; Año: 2015 vol. 415 p. 100 - 100
Considering that the role of ERb in the growth of pituitary cells is not well known, the aim of this workwas to de termine the expression of ERb in normal and tumoral cells and to investigate its implications in the proliferative control of this endocrine gland, by analyzing the participation of cyclin D1, Cdk4 andp21. Our results showed that the expression of ERb decreased during pituitary tumoral development induced by chronic E2 stimulation. The 20 ± 1.6% of normal adenohypophyseal cells expressed ERb, with this protein being reduced in the hyperplastic/adenomatous pituitary: at 20 days the ERb population was 10.7 ± 2.2%, while after 40 and 60 days of treatment an almost complete loss in the ERb expression was observed (40d: 1 ± 0.6%; 60d: 2 ± 0.6%). The ERa/b ratio increased starting from tumors at 40 days, mainly due to the loss of ERb expression. The cell proliferation was analyzed in normal and hyperplasticpituitary and also in GH3b and GH3bþ which contained different levels of ERb expression, and therefore different ERa/b ratios. The over-expression of ERb inhibited the GH3 cell proliferation and expression of cyclin D1 and ERa. Also, the ERb activation by its agonist DPN changed the subcellular localization of p21, inducing an increase in the p21 nuclear expression, where it acts as a tumoral suppressor. These results show that ERb exerts an inhibitory role on pituitary cell proliferation, and that this effect may be partially due to the modulation of some key regulators of the cell cycle, such as cyclin D1 and p21. These data contribute significantly to the understanding of the ER effects in the proliferative control of pituitary gland, specifically related to the ERb function in the E2 actions on this endocrine gland.