Hormonal regulation of human trophoblast differentiation: a possible role for 17beta-estradiol and GnRH.
We have examined the role of 17beta-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 17beta-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 p27(Kip1). The anti-proliferative effects of 17beta-estradiol were annulled by specific transforming growth factor-beta 1 (TGFbeta1)-neutralizing antibody, suggesting that 17beta-estradiol may mediate its growth-inhibitory actions, through TGFbeta1 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 functional GnRH receptors. Preliminary studies on the characterization of the human placental GnRH receptor, indicate the presence of multiple receptor isoforms across human gestation.
Rama
S
S
Department of Biochemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India.
Petrusz
P
P
Rao
A J
AJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D019925:Cyclin A / Q000378:metabolism; D056751:Cyclin A2; D019927:Cyclin E / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
C503721:CCNA2 protein, human; C503722:Ccna2 protein, rat; D019925:Cyclin A; D056751:Cyclin A2; D019927:Cyclin E; D006727:Hormone Antagonists; D011960:Receptors, Estrogen; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; C062876:cetrorelix