Estradiol Upregulates c-FLIPlong Expression in Anterior Pituitary Cells

JAITA G; ZÁRATE S; FERRARIS J; GOTTARDO MF; EIJO G; MAGRI ML; PISERA D; SEILICOVICH A

HORMONE AND METABOLIC RESEARCH

GEORG THIEME VERLAG KG

Año: 2016

0018-5043

Anterior pituitary cell turnover depends on a tight balance between proliferation and apoptosis. We previously showed that estrogens sensitize anterior pituitary cells to pro-apoptotic stimuli. c-FLIP (cellular-FLICE-inhibitory-protein) isoforms are regulatory proteins of apoptosis triggered by death receptors. c-FLIPshort isoform competes with procaspase-8 inhibiting its activation. However, c-FLIPlong isoform may have a pro- or anti-apoptotic function depending on its expression level. In the present study, we explored whether estrogens modulate c-FLIP expression in normal and tumoral anterior pituitary cells. Acute administration of 17β-estradiol to ovariectomized rats increased c-FLIPlong expression in the anterior pituitary gland without changing c-FLIPshort expression as assesed by Western blot. Estradiol in vitro also increased c-FLIPlong expression in normal anterior pituitary cells but not in GH3 cells, a somatolactotrope cell line. As determined by flow cytometry, the percentage of normal anterior pituitary cells expressing c-FLIP was higher than in GH3 cells. However, c-FLIP fluorescence intensity in GH3 cells was higher than in normal anterior pituitary cells. FasL increased the percentage of TUNEL-positive GH3 cells incubated either with or without estradiol suggesting that the propapoptotic action of Fas activation is estrogen-independent. Our results show that, unlike what happens in normal anterior pituitary cells, estrogens do not modulate neither c-FLIPlong expression nor FasL-induced apoptosis in GH3 cells. The stimulatory effect of estradiol on c-FLIPlong expression could be involved in the sensitizing effect of this steroid to apoptosis in normal anterior pituitary cells. The absence of this estrogenic action in tumor pituitary cells could be involved in their tumor-like behavior.