Progesterone Antagonizes the Permissive Action of Estradiol on Tumor Necrosis Factor Alfa Induced Apoptosis of Anterior Pituitary Cells

M. CANDOLFI; G. JAITA; V. ZALDIVAR; S. ZARATE; L. FERRARI; D. PISERA; M. G. CASTRO; A. SEILICOVICH

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2005 p. 736 - 743

0013-7227

We previously reported that TNF-á-induced apoptosis of lactotropes is estrogen-dependent and predominant at proestrus. Here, we observed that TNF-á (50 ng/ml) failed to induce apoptosis of anterior pituitary cells from OVX rats cultured in the presence of progesterone (10-6M). However, progesterone blocked the apoptotic effect of TNF-á in anterior pituitary cells and lactotropes cultured with 17b-estradiol (10-9M). In addition, 17b-estradiol induced apoptosis of somatotropes and triggered the proapoptotic action of TNF-á in these cells, effects completely blocked by ICI 182 780 (10-6M), an estrogen receptor antagonist. Progesterone reverted the permissive effect of 17b-estradiol on TNF-a-induced apoptosis of somatotropes. TNF-á induced apoptosis of somatotropes from rats killed at proestrus but not at diestrus. The antiprogestine ZK 98 299 (10-6M) completely inhibited the protective action of progesterone on TNF-á-induced apoptosis of anterior pituitary cells, lactotropes and somatotropes. Although progesterone can interact with glucocorticoid receptors, dexamethasone (10-6M) had no effect on TNF-a-induced apoptosis of anterior pituitary cells, lactotropes and somatotropes. Our results show that progesterone, by interacting with progesterone receptors, antagonizes the permissive action of estrogens on TNF-á-induced apoptosis of lactotropes and somatotropes. These observations suggest that the steroid milieu may modulate the apoptotic response of anterior pituitary cells during the estrous cycle.