Influence of 17beta-Estradiol on the Fas/FasL System in the Anterior Pituitary.

JAITA G; CANDOLFI M; ZALDIVAR V; FERRARI L; PISERA D; CASTRO MG; SEILICOVICH A

Congreso; 87º Annual Meeting Endocrine Society; 2005

A growing body of evidence suggests that during the estrous cycle anterior pituitary cell turnover is regulated by gonadal steroid hormones. We previously showed that Fas activation induces apoptosis of anterior pituitary cells and that the expression of Fas and FasL is higher in anterior pituitary cells from rats killed at proestrus than at diestrus, suggesting that estrogens could modulate the expression of Fas and FasL in the anterior pituitary during the estrous cycle. Therefore, we determined the expression of Fas and FasL by immunocytochemistry in anterior pituitary cells from OVX rats incubated with or without 17b-estradiol (10-9M, E). 17b-estradiol increased the percentage of anterior pituitary cells expressing either Fas (C: 17 %, E: 27 %, p<0.001, chi2) or FasL (C: 31 %, E: 40%, p<0.001). Also, 17b-estradiol increased the percentage of lactotropes with positive staining for Fas (C: 21 %, E: 27 %, p<0.001) and FasL as well (C: 20 %, E: 36 %, p<0.001). Although this steroid increased the percentage of somatotropes immunoreactive for Fas (C: 55 %, E: 65 %, p<0.05) it failed to affect FasL expression in this cells (C: 81 %, E: 87 %, ns). To explore the influence of 17b-estradiol on the apoptosis triggered by Fas activation we determined the percentage of TUNEL positive anterior pituitary cells incubated with a monoclonal antibody (Mab-Fas) with agonistic activity. Mab-Fas (1mg/ml) increased the percentage of apoptotic anterior pituitary cells from OVX rats incubated either in the absence or presence of 17b-estradiol (OVX: 3 %, OVX+Mab-Fas: 5 %, p<0.05; E: 4%, E+Mab-Fas: 10 %, p<0.001). Nevertheless, the apoptotic effect of Mab-Fas was higher in the presence of 17b-estradiol than in its absence (p<0.001). Mab-Fas increased the percentage of apoptotic somatotropes incubated either with or without 17b-estradiol (OVX: 12 %, OVX+Mab-Fas: 23 %, p<0.001; E: 9 % E+Mab-Fas: 18 % p<0.001). However, lactotropes underwent Mab-Fas-induced apoptosis only when they were cultured with 17b-estradiol (OVX: 9 %, OVX+Mab-Fas: 8 %, ns; E: 10 %, E+Mab-Fas: 25 %, p<0.001).Our results show that 17b-estradiol stimulates the expression of the Fas/FasL system in anterior pituitary cells and increases Fas-induced apoptosis. The expression of the Fas/FasL system and the apoptotic response to Fas activation may be regulated by estrogens in a cell-type specific manner, suggesting that the Fas/FasL system could be involved in anterior pituitary cell renewal during the estrous cycle.