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This version published online on November 4, 2004
Endocrinology, doi:10.1210/en.2004-1276
A more recent version of this article appeared on February 1, 2005
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Submitted on September 28, 2004
Accepted on October 25, 2004

PROGESTERONE ANTAGONIZES THE PERMISSIVE ACTION OF ESTRADIOL ON TNF-{alpha}-INDUCED APOPTOSIS OF ANTERIOR PITUITARY CELLS

M. Candolfi, G. Jaita, V. Zaldivar, S. Zárate, L. Ferrari, D. Pisera, M. G. Castro, and A. Seilicovich*

Centro de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires (C1121ABG), Argentina; Gene Therapeutics Research Institute, Cedars Sinai Medical Center and David Geffen School of Medicine, UCLA, Los Angeles, California 90048, USA

* To whom correspondence should be addressed. E-mail: adyseili{at}fmed.uba.ar.

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 OVX rats cultured in the presence of progesterone (10-6M). However, progesterone blocked the apoptotic effect of TNF-{alpha} in anterior pituitary cells and lactotropes cultured with 17{beta}-estradiol (10-9M). In addition, 17{beta}-estradiol induced apoptosis of somatotropes and triggered the proapoptotic action of TNF-{alpha} in these cells, effects completely blocked by ICI 182 780 (10-6M), an estrogen receptor antagonist. Progesterone reverted the permissive effect of 17{beta}-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 (10-6M) 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 (10-6M) 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.
Key words: TNF-{alpha} • progesterone • estrogen • estrous cycle • pituitary • apoptosis




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