Non-classical estrogen apoptotic action in the anterior pituitary gland

S. ZARATE; G.JAITA,; J. FERRARIS; G. EIJO; D. RADL; V.ZALDIVAR; M. L. MAGRI; D.PISERA; A. SEILICOVICH

Quebec

Congreso; 5th Annual Canadian Neuroscience Meeting; 2011

In the adult female rat, estrogens are thought to be key players in the cyclic processes of proliferation and death that anterior pituitary cells undergo along the estrous cycle. Although estrogens are known to exert a trophic stimulus on anterior pituitary mitotic activity, the rate of anterior pituitary cell apoptosis has a peak at proestrous, when estrogen levels are the highest. Estrogen actions in this gland are exerted through both classical and non-classical mechanisms of action, the latter involving the activation of estrogen receptors (ERs) associated to the plasma membrane. We have shown that a membrane-impermeant 17beta-estradiol conjugate induces a rapid apoptotic action in anterior pituitary cells, lactotropes and somatotropes from ovariectomized (OVX) female Wistar rats. This effect is completely abrogated by ICI 182,780, the pure antagonist of ERs, suggesting the involvement of classical ERs associated to the plasma membrane. Also, an estrogen-dendrimer conjugate, whose action is restricted to sites near the cell surface, has a rapid apoptotic effect in anterior pituitary cells. The identity of membrane ERs is still a matter of controversy. In cycling rats, we have detected a higher number of lactotropes and a lower number of somatotropes expressing a membrane form of the classical ERalpha (mERalpha) at proestrous than at diestrus. In OVX rats, the acute treatment with E2 increased the number of mERalpha-expressing lactotropes whereas progesterone treatment abrogated this estrogenic effect. We are currently working on the characterization of membrane-associated estrogen receptor/s and intracellular signaling pathways involved in estradiol proapoptotic action in anterior pituitary cells.