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

Abstract

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 17beta-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 vi-ability-3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay)-of anterior pituitary cells from OVX rats cultured in the presence of 17beta-estradiol. Also, membrane-bound FasL decreased cell viability-[3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay (MTS assay)-only when anterior pituitary cells from OVX rats were incubated with 17beta-estradiol. Moreover, FasL increased the percentage of hypodiploid anterior pituitary cells (flow cytometry). Mab-Fas increased the percentage of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive pituitary cells and lactotropes from OVX rats only when cells were incubated in the presence of 17beta-estradiol. Also, Mab-Fas triggered apoptosis of anterior pituitary cells from rats killed at proestrus but not at diestrus. Our results show that 17beta-estradiol up-regulates 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.

RGD-FasL Induces Apoptosis of Pituitary Adenoma Cells

“…Interestingly, Candolfi et al had reported that Fas activation induces apoptosis of anterior pituitary cells from female rats, suggesting that FasL is involved in the maintenance of tissue homeostasis in the anterior pituitary gland and could have potential benefits for the treatment of pituitary adenomas (18)(19)(20)(21). In the present study, we detected the expressions of Fas and DcR3 on 3 pituitary adenoma cell lines.…”

“…Jaita et al detected that Fas and FasL are expressed in several anterior pituitary cell types from female rats, mainly in lactotropes and somatotropes. In addition, they reported that Fas activation induces apoptosis of lactotropes and somatotropes as well (21). It was also demonstrated that the somatolactotrophic tumor GH3 cell line and the corticotrophic tumor AtT20 cell line express Fas (31,32).…”

Adenoviral vectors encoding tumor necrosis factor-α and FasL induce apoptosis of normal and tumoral anterior pituitary cells

“…In fact, our present data show that overexpression of TNF-in primary anterior pituitary cell cultures induced apoptosis of prolactin-and growth hormonebearing cells. We previously detected the expression of FasL and Fas in several anterior pituitary cell types from female rats, mainly in lactotropes and somatotropes (Jaita et al 2005b). In addition, we reported that Fas activation induces apoptosis of lactotropes (Jaita et al 2005b) and somatotropes as well (Jaita et al 2005a).…”

“…Our previous work showed that both TNF-and FasL induce apoptosis of anterior pituitary cells (Candolfi et al 2002, Jaita et al 2005b). Now, we overexpressed TNF-and FasL in primary cultures of anterior pituitary cells by infecting them with first-generation adenoviral vectors encoding TNF-(RAd-hCMV-TNF-), FasL (RAd-hCMV-FasL) or, as a control, -Gal (RAd-hCMV--Gal), under the control of the human cytomegalovirus promoter (hCMV).…”

“…We have previously reported that TNFR1 and Fas activation induce apoptosis of anterior pituitary cells from female rats (Candolfi et al 2002, Jaita et al 2005b suggesting that TNF-and FasL are involved in the maintenance of tissue homeostasis in the anterior pituitary gland and could have potential benefits for the treatment of pituitary diseases. Although major advances have been made in the therapy of pituitary tumors, only partial success has been possible and novel therapies are needed.…”