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Hormonal regulation of human trophoblast differentiation: a possible role for 17$\beta$-estradiol and GnRH

Rama, S and Petrusz, P and Rao, AJ (2004) Hormonal regulation of human trophoblast differentiation: a possible role for 17$\beta$-estradiol and GnRH. In: Molecular and Cellular Endocrinology, 218 (1-2). pp. 79-94.

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We have examined the role of 17$\beta$-estradiol and gonadotropin releasing hormone GnRH) in the regulation of functional differentiation in human trophoblasts. In contrast to its recognized functions as a proliferation-promoting hormone in a variety of cell types, we found that 17$\beta$-estradiol induced terminal differentiation in human trophoblastic cells, and that this event was estrogen-receptor-mediated. This process involved a loss in expression of Cyclins A2 and E, and a coincident increase in $p^{27 Kip1.}$ The anti-proliferative effects of 17$\beta$-estradiol were annulled by specific transforming growth factor-beta 1 $(TGF\beta1)$-neutralizing antibody, suggesting that 17$\beta$-estradiol may mediate its growth-inhibitory actions, through $TGF\beta1$ activity. Following exposure to Buserelin, cultured human trophoblastic cells stopped proliferating and formed functionally mature syncytiotrophoblasts. This differentiation event, that involved a drastic loss in expression of proliferating-cell-nuclear-antigen, could be blocked by Cetrorelix, suggesting the involvement of functionalGnRHreceptors. Preliminary studies on the characterization of the human placental GnRH receptor, indicate the presence of multiple receptor isoforms across human gestation.

Item Type: Journal Article
Publication: Molecular and Cellular Endocrinology
Publisher: Elsevier
Additional Information: The copyright belongs to Elsevier.
Keywords: Differentiation;Estradiol;GnRH;Proliferation;TGFβ1;Trophoblast
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Division of Biological Sciences > Biochemistry
Date Deposited: 10 May 2006
Last Modified: 19 Sep 2010 04:26
URI: http://eprints.iisc.ac.in/id/eprint/6660

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