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/RXR
Heterodimers Are Involved in Human CGß Synthesis and Human Trophoblast Differentiation
Unité Institut National de la Santé et de la Recherche Médicale 427 (A.T., J.G., D.E.-B.), Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Université René Descartes, Paris V, 75006 Paris, France; Institut de Génétique et Biologie Moléculaire et Cellulaire (K.S., J.A., C.R.-E.), Université Louis Pasteur, BP163, 67404 Illkirch cedex, France; CNRS UPRES-A 8067 (J.M.B.), Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, France; and Laboratoire de Génétique Moléculaire (M.V.), Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris V, 75006 Paris, France
Address all correspondence and requests for reprints to: Danièle Evain-Brion, Institut National de la Santé et de la Recherche Médicale Unité 427, Faculté des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l’Observatoire, 75006 Paris, France. E-mail: evain{at}pharmacie.univ-paris5.fr
Recent studies performed with null mice suggested a role of either
RXR
or PPAR
in murine placental development. We report here that
both PPAR and RXR are strongly expressed in human villous
cytotrophoblasts and syncytiotrophoblasts. Moreover, specific ligands
for RXRs or PPAR (but not for PPAR or PPAR
) increase both
human CGß transcript levels and the secretion of human CG and its
free ß-subunit. When combined, these ligands have an additive
effect on human CG secretion. Pan-RXR and PPAR 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/RXR heterodimers are
functional units during cytotrophoblast differentiation into the
syncytiotrophoblast in vitro. Elements located in the
regulatory region of the human CGß gene (ß5) were found to bind
RXR and PPAR from human cytotrophoblast nuclear extracts,
suggesting that PPAR/RXR heterodimers directly regulate human
CGß transcription. Altogether, these data show that PPAR/RXR
heterodimers play an important role in human placental
development.
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