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Am J Physiol Endocrinol Metab 296: E664-E671, 2009. First published January 21, 2009; doi:10.1152/ajpendo.90785.2008
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Estrogens exert a rapid apoptotic action in anterior pituitary cells

S. Zárate, G. Jaita, V. Zaldivar, D. B. Radl, G. Eijo, J. Ferraris, D. Pisera, and A. Seilicovich

Facultad de Medicina, Instituto de Investigaciones en Reproducción, Universidad de Buenos Aires, Paraguay, Buenos Aires, Argentina

Submitted 22 September 2008 ; accepted in final form 13 January 2009

It is now accepted that estrogens not only stimulate lactotrope proliferation but also sensitize anterior pituitary cells to proapoptotic stimuli. In addition to their classical mechanism of action through binding to intracellular estrogen receptors (ERs), there is increasing evidence that estrogens exert rapid actions mediated by cell membrane-localized ERs (mERs). In the present study, we examined the involvement of membrane-initiated steroid signaling in the proapoptotic action of estradiol in primary cultures of anterior pituitary cells from ovariectomized rats by using estren, a synthetic estrogen with no effect on classical transcription and a cell-impermeable 17β-estradiol conjugate (E2-BSA). Both compounds induced cell death of anterior pituitary cells after 60 min of incubation as assessed by flow cytometry and the [3-(4,5-dimethylthiazol-2-yl)]-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Estren, E2, and E2-BSA induced apoptosis of lactotropes and somatotropes as evaluated by the deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and immunodetection of prolactin (PRL) and growth hormone (GH). The proapoptotic effect of E2-BSA was abrogated by ICI-182,780, an antagonist of ERs. The expression of membrane-associated ER{alpha} was observed in PRL- and GH-bearing cells. Our results indicate that estradiol is able to exert a rapid apoptotic action in anterior pituitary cells, especially lactotropes and somatotropes, by a mechanism triggered by mERs. This mechanism could be involved in anterior pituitary cell turnover.

estrogen; membrane receptors; pituitary; lactotropes; somatotropes; apoptosis



Address for reprint requests and other correspondence: A. Seilicovich, Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, piso 10, Buenos Aires (C1121ABG), Argentina (e-mail: adyseili{at}fmed.uba.ar)







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