Estradiol increases the Bax/Bcl-2 ratio and induces apoptosis in the anterior pituitary gland.

ZALDIVAR V; MAGRI ML; ZÁRATE S; JAITA G; EIJO G; FERRARIS J; PISERA D; SEILICOVICH A

NEUROENDOCRINOLOGY

KARGER

Año: 2009 vol. 90 p. 292 - 300

0028-3835

Abstract Estrogens are now recognized to act as modulators of pituitary cell renewal, sensitizing cells to both mitogenic and apoptotic signals, thus participating in anterior pituitary (AP) tissue homeostasis during the estrous cycle. The balance of pro and antiapoptotic proteins of the Bcl-2 family is known to regulate cell survival and apoptosis. To understand the mechanisms underlying apoptosis during the estrous cycle, we evaluated the expression of the proapoptotic protein Bax and the antiapoptotic proteins Bcl-2 and Bcl-xL in the AP gland in cycling female rats, and the influence of estradiol on the expression of these proteins in ovariectomized (OVX) rats. As determined by Western Blot, expression of Bax was higher in AP glands from rats at proestrus than at diestrus I. Although Bcl-2 protein levels showed no significant difference between these two stages of the estrous cycle, Bcl-xL expression was lower in the AP from rats at proestrus than at diestrus I. Also,  the percentage of apoptotic AP cells, as assessed by Annexin-V binding and flow cytometry, was higher in rats at proestrus than at diestrus I. Chronic estrogen treatment, through implants containing 1 mg of 17b-estradiol to OVX rats, enhanced the Bax/Bcl-2 ratio and induced apoptosis in the AP gland. Moreover, incubation of cultured AP cells from OVX rats with 17b-estradiol (10-9 M) for 24 h increased the Bax/Bcl-2 ratio, decreased Bcl-xL expression and induced apoptosis. Taken together, our results demonstrate that estradiol increases the ratio between proapoptotic and antiapoptotic proteins of the Bcl-2 family. This effect could participate in the sensitizing action of estrogens to proapoptotic stimuli in AP cells and could be involved in the high apoptotic rate observed at proestrus in the AP gland.