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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
-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
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