Progesterone antagonizes the permissive action of estradiol on tumor necrosis factor-alpha-induced apoptosis of anterior pituitary cells.
We previously reported that TNF-alpha-induced apoptosis of lactotropes is estrogen dependent and predominant at proestrus. Here we observed that TNF-alpha (50 ng/ml) failed to induce apoptosis of anterior pituitary cells from ovariectomized rats cultured in the presence of progesterone (10(-6) m). However, progesterone blocked the apoptotic effect of TNF-alpha in anterior pituitary cells and lactotropes cultured with 17beta-estradiol (10(-9) m). In addition, 17beta-estradiol induced apoptosis of somatotropes and triggered the proapoptotic action of TNF-alpha in these cells, effects completely blocked by ICI 182 780 (10(-6) m), an estrogen receptor antagonist. Progesterone reverted the permissive effect of 17beta-estradiol on TNF-alpha-induced apoptosis of somatotropes. TNF-alpha induced apoptosis of somatotropes from rats killed at proestrus but not at diestrus. The antiprogestine ZK 98,299 (10(-6) m) completely inhibited the protective action of progesterone on TNF-alpha-induced apoptosis of anterior pituitary cells, lactotropes, and somatotropes. Although progesterone can interact with glucocorticoid receptors, dexamethasone (10(-6) m) had no effect on TNF-alpha-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-alpha-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.
Candolfi
M
M
Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 10, Buenos Aires 1121, Argentina.
Jaita
G
G
Zaldivar
V
V
Zárate
S
S
Ferrari
L
L
Pisera
D
D
Castro
M G
MG
Seilicovich
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005938:Glucocorticoids; D011980:Receptors, Progesterone; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone