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Am J Physiol Endocrinol Metab 297: E676-E684, 2009. First published June 16, 2009; doi:10.1152/ajpendo.91020.2008
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Prolactin independent rescue of mouse corpus luteum life span: identification of prolactin and luteinizing hormone target genes

Anne Bachelot,1,2,3 Julie Beaufaron,1,2 Nathalie Servel,1,2 Cécile Kedzia,1,2 Philippe Monget,4 Paul A. Kelly,1,2 Geula Gibori,5 and Nadine Binart1,2

1Institut National de la Santé et de la Recherche Médicale, Unité 845, Paris; 2Faculté de Médecine, Université Paris Descartes, Paris; 3Endocrinology and Reproductive Medicine, Pitié-Salpétrière Hospital, Paris; 4Unité Mixte de Recherche 6175, Institut National de la Recherche Agronomique, Reproductive Physiology and Behavior, Nouzilly, France; and 5Department of Physiology and Biophysics, University of Illinois, Chicago, Illinois

Submitted 19 December 2008 ; accepted in final form 15 June 2009

The corpus luteum (CL) plays a central role in the maintenance of pregnancy in rodents, mainly by secreting progesterone. Female mice lacking prolactin (PRL) receptor (R) are sterile due to a failure of embryo implantation, which is a consequence of decreased luteinizing hormone (LH) receptor expression in the CL and inadequate levels of progesterone. We attempted to treat PRLR–/– females with human chorionic gonadotropin (hCG) and showed a de novo expression of LHR mRNA in the corpora lutea. Binding analysis confirmed that the LHR in hCG-treated PRLR–/– animals was functional. This was accompanied with increased expression of steroidogenic enzymes involved in progesterone synthesis. Despite these effects, no embryo implantation was observed because of high expression of 20{alpha}-hydroxysteroid dehydrogenase. To better appreciate the molecular mechanisms underlying maintenance of the CL, a series of mRNA expression-profiling experiments was performed on isolated corpora lutea of PRLR–/– and hCG-treated PRLR–/– mice. This approach revealed several novel candidate genes with potentially pivotal roles in ovarian function, among them, p27, VE-cadherin, Pten, and sFRP-4, a member of the Wnt/frizzled family. This study showed the differential role of PRL and LH in CL function and identified new targets of these hormones in luteal cells.

prolactin receptor; luteinizing hormone receptor; corpus luteum



Address for reprint requests and other correspondence: N. Binart, INSERM, U845, 156 rue de Vaugirard, Paris 75015, France (e-mail: nadine.binart{at}inserm.fr)







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