Gonadal steroids alter the balance between pro and antiapoptotic members of the Bcl-2 family in the anterior pituitary

ZALDIVAR VERÓNICA; EIJO GUADALUPE; ZÁRATE SANDRA; JAITA GABRIELA; RADL DANIELA; PISERA DANIEL; SEILICOVICH ADRIANA

Toronto

Congreso; 89th Annual Meeting of the Endocrine Society; 2007

  We previously demonstrated that the apoptotic effect induced either by TNF-a or Fas activation in anterior pituitary cells from female rats (especially lactotropes) is estrogen-dependent and higher in cells from rats at proestrus (when estradiol levels are the highest) than at diestrus (1,2). In addition, we have shown that estradiol not only potentiates the proapoptotic effect of TNF-a in somatotropes, but also has an apoptotic action per se in this pituitary cell subpopulation (3). The balance between pro and antiapoptotic signaling pathways determines the fate of a cell in response to external or internal stimuli. Considering that the Bcl-2 family members have been implicated as major regulators of the cell death machinery, we investigated  the expression of Bax, a proapoptotic protein of the Bcl-2 family and Bcl-2 and Bcl-XL, two antiapoptotic members of this family. These proteins were analyzed by Western Blot in anterior pituitaries of Wistar rats killed at selected stages of the estrous cycle and in anterior pituitary cells from ovariectomized (OVX) rats cultured in the presence of 17â-estradiol (E2, 10-9 M) .               In cycling rats, Bax expression was two-fold higher whereas the expression of Bcl-XL was slightly lower (16%) in the anterior pituitary of rats killed at proestrus than at diestrus. In cultured anterior pituitary cells from OVX rats the expression of Bax was increased by 35% (p<0.05) whereas the expression of Bcl-XL was decreased by 25%  (p<0.05) when cells were incubated in the presence of E2. We observed no differences between the expression of Bcl-2 in the anterior pituitary of rats at proestrus and diestrus nor in cultured anterior pituitary cells incubated in the presence or absence of E2. Taken together these results indicate that estrogens, by increasing the balance of proapoptotic versus antiapoptotic proteins of the Bcl-2 family could sensitize anterior pituitary cells to apoptotic stimuli at proestrus. 1) Candolfi M et al., TNF-alpha induces apoptosis of lactotropes from female rats. Endocrinology 2002 143:3611-3617. 2) Jaita G et al., Estrogens up-regulate the Fas/FasL apoptotic pathway in lactotropes. Endocrinology 2005 146:4737-4744. 3) Candolfi M et al., Progesterone antagonizes the permissive action of estradiol on tumor necrosis factor-alpha-induced apoptosis of anterior pituitary cells. Endocrinology 2005 146:736-43.