Prolactin independent rescue of mouse corpus luteum life span: identification of prolactin and luteinizing hormone target genes.
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 20alpha-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.
Bachelot
Anne
A
Institut National de la Santé et de la Recherche Médicale, Unité 845, Paris, France.
Beaufaron
Julie
J
Servel
Nathalie
N
Kedzia
Cécile
C
Monget
Philippe
P
Kelly
Paul A
PA
Gibori
Geula
G
Binart
Nadine
N
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003340:Corpus Luteum Maintenance / Q000097:blood / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D007986:Luteinizing Hormone / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D011388:Prolactin / Q000494:pharmacology / Q000502:physiology*; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics
D006063:Chorionic Gonadotropin; D011974:Receptors, LH; D011981:Receptors, Prolactin; D011374:Progesterone; D011388:Prolactin; D007986:Luteinizing Hormone