Submitted on December 19, 2008
Revised on June 5, 2009
Accepted on June 15, 2009
Prolactin independent rescue of mouse corpus luteum life span: identification of prolactin and luteinizing hormone target genes
Anne Bachelot1, Julie Beaufaron1, Nathalie Servel1, Cécile Kedzia1, Philippe Monget2, Paul A Kelly1, Geula Gibori3, and Nadine Binart1*
1 Inserm U 845
2 UMR 6175, INRA
3 University of Illinois at Chicago College of Medicine
* To whom correspondence should be addressed. E-mail: nadine.binart{at}inserm.fr.
The corpus luteum (CL) plays a central role in the maintenance of pregnancy in rodents, mainly by secreting progesterone. Female mice lacking PRL receptor (R) are sterile due to a failure of embryo implantation which is a consequence of decreased LH receptor expression in the CL and inadequate levels of progesterone. We attempted to treat PRLR-/- females with 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, due to high expression of 20-hydroxysteroid dehydrogenase. To better appreciate the molecular mechanisms underlying maintenance of the corpus luteum, 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 corpus luteum function and identified new targets of these hormones in luteal cells.
