Estrogens Up-Regulate the Fas/FasL Apoptotic Pathway in Lactotropes

G. JAITA; M. CANDOLFI; V. ZALDIVAR; S. ZARATE; L. FERRARI; D. PISERA; M. G. CASTRO; A. SEILICOVICH

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2005 p. 4737 - 4744

0013-7227

The Fas/FasL system provides the major apoptotic mechanism for many cell types, participating in cell turnover in hormone-dependent tissues. In the present study we localized both Fas and FasL in anterior pituitary cells, mainly in lactotropes and somatotropes. The percentage of anterior pituitary cells showing immunoreactivity for Fas or FasL was higher in cells from rats killed in proestrus than in diestrus. Also, the proportion of pituitary cells from ovariectomized (OVX) rats expressing Fas or FasL increased in the presence of 17b-estradiol (10-9 M). This steroid increased the percentage of lactotropes with immunoreactivity for Fas or FasL and the percentage of somatotropes expressing Fas. Activation of Fas by an agonist anti-Fas antibody (Mab-Fas) decreased the viability (MTT assay) of anterior pituitary cells from OVX rats cultured in the presence of 17b-estradiol. Also, membrane-bound FasL decreased  cell viability (MTS assay) only when anterior pituitary cells from OVX rats were incubated with 17b-estradiol. Moreover, FasL increased the percentage of hypodiploid anterior pituitary cells (flow cytometry). Mab-Fas increased the percentage of TUNEL-positive pituitary cells and lactotropes from OVX rats only when cells were incubated in the presence of 17b-estradiol. Also, Mab-Fas triggered apoptosis of anterior pituitary cells from rats killed at proestrus but not at diestrus. Our results show that 17b-estradiol upregulates the expression of the Fas/FasL system in anterior pituitary cells and increases Fas-induced apoptosis in lactotropes, suggesting that Fas-induced apoptosis could be involved in the pituitary cell renewal during the estrous cycle.