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Retinoids Stimulate Leptin Synthesis and Secretion in Human Syncytiotrophoblast¹

INSERM U-427 (J.G., A.T., D.E.-B.) and Laboratoire de Génétique Moléculaire, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes Paris V (I.L., M.V.), 75006 Paris; and Centre National de la Recherche Scientifique/INSERM/Université Louis Pasteur (C.R.-E., P.C.), 67404 Illkirch, France

Address all correspondence and requests for reprints to: Dr. Danièle Evain-Brion, INSERM U-427, Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Université René Descartes, 4 avenue de l’Observatoire, 75006 Paris, France. E-mail: u427{at}pharmacie.univ-paris5.fr

The syncytiotrophoblast (ST), which forms the outer layer of the chorionic villi, is the endocrine unit of the human placenta. Bathing in the maternal blood of the intervillous space, the ST secretes its hormonal products directly into the maternal circulation. Leptin is expressed in the ST and is secreted into the maternal circulation. However, its regulation and physiological role during pregnancy remain poorly known. In the present work we used the in vitro model of human cytotrophoblast differentiation into ST to study the effect of physiological and synthetic retinoids on leptin synthesis and secretion. Using specific antibodies we first illustrated by immunocytochemistry the expression of retinoic acid (RA) receptor and retinoid X receptor (RXR) in ST. We then observed that leptin messenger ribonucleic acid and protein expression increased with in vitro ST formation. The 9-cis isomer of RA and the synthetic retinoid specific for RXRs (BMS 649) stimulated leptin messenger ribonucleic acid expression and secretion. In contrast, all-trans-RA and a RA -specific ligand had no effect. These results suggest that retinoids regulate leptin expression and highlight a role for RXR in this process.

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