PPAR gamma/RXR alpha heterodimers are involved in human CG beta synthesis and human trophoblast differentiation

Recent studies performed with null mice suggested a role of either RXR alpha or PPAR gamma in murine placental development. We report here that both PPAR gamma and RXR alpha are strongly expressed in human villous cytotrophoblasts and syncytiotrophoblasts. Moreover, specific ligands for RXRs or PPAR...

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Published in:Endocrinology (Philadelphia) 2001-10, Vol.142 (10), p.4504-4514
Main Authors: Tarrade, A, Schoonjans, K, Guibourdenche, J, Bidart, J M, Vidaud, M, Auwerx, J, Rochette-Egly, C, Evain-Brion, D
Format: Article
Language:English
Subjects:
Cell Differentiation - physiology
Cells, Cultured
Chorionic Gonadotropin, beta Subunit, Human - physiology
Dimerization
Female
Humans
Receptors, Cytoplasmic and Nuclear - physiology
Receptors, Retinoic Acid - physiology
Retinoid X Receptors
Signal Transduction
Transcription Factors - physiology
Trophoblasts - cytology
Trophoblasts - physiology
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Summary:Recent studies performed with null mice suggested a role of either RXR alpha or PPAR gamma in murine placental development. We report here that both PPAR gamma and RXR alpha are strongly expressed in human villous cytotrophoblasts and syncytiotrophoblasts. Moreover, specific ligands for RXRs or PPAR gamma (but not for PPAR alpha or PPAR delta) increase both human CG beta transcript levels and the secretion of human CG and its free beta-subunit. When combined, these ligands have an additive effect on human CG secretion. Pan-RXR and PPAR gamma ligands also have an additive effect on the synthesis of other syncytiotrophoblast hormones such as human placental lactogen, human placental GH, and leptin. Therefore, in human placenta, PPAR gamma/RXR alpha heterodimers are functional units during cytotrophoblast differentiation into the syncytiotrophoblast in vitro. Elements located in the regulatory region of the human CG beta gene (beta 5) were found to bind RXR alpha and PPAR gamma from human cytotrophoblast nuclear extracts, suggesting that PPAR gamma/RXR alpha heterodimers directly regulate human CG beta transcription. Altogether, these data show that PPAR gamma/RXR alpha heterodimers play an important role in human placental development.
ISSN:0013-7227
DOI:10.1210/en.142.10.4504