title: Effects of deletion of the prolactin receptor on ovarian gene expression.
abstract: Prolactin (PRL) exerts pleiotropic physiological effects in various cells and tissues, and is mainly considered as a regulator of reproduction and cell growth. Null mutation of the PRL receptor (R) gene leads to female sterility due to a complete failure of embryo implantation. Pre-implantatory egg development, implantation and decidualization in the mouse appear to be dependent on ovarian rather than uterine PRLR expression, since progesterone replacement permits the rescue of normal implantation and early pregnancy. To better understand PRL receptor deficiency, we analyzed in detail ovarian and corpora lutea development of PRLR-/- females. The present study demonstrates that the ovulation rate is not different between PRLR+/+ and PRLR-/- mice. The corpus luteum is formed but an elevated level of apoptosis and extensive inhibition of angiogenesis occur during the luteal transition in the absence of prolactin signaling. These modifications lead to the decrease of LH receptor expression and consequently to a loss of the enzymatic cascades necessary to produce adequate levels of progesterone which are required for the maintenance of pregnancy.
authors.affiliation: Molecular Endocrinology, INSERM U344 Faculté de Médecine Necker-Enfants Malades, 75730 Paris Cedex 15, France. grosdemouge@necker.fr
authors.forename: Isabelle
authors.initials: I
authors.lastname: Grosdemouge
authors.forename: Anne
authors.initials: A
authors.lastname: Bachelot
authors.forename: Aurélie
authors.initials: A
authors.lastname: Lucas
authors.forename: Nathalie
authors.initials: N
authors.lastname: Baran
authors.forename: Paul A
authors.initials: PA
authors.lastname: Kelly
authors.forename: Nadine
authors.initials: N
authors.lastname: Binart
mesh_terms: D043607:20-alpha-Hydroxysteroid Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D015096:3-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000096:biosynthesis / Q000235:genetics; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000502:physiology; D056742:Cyclin D2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D010064:Embryo Implantation / Q000235:genetics / Q000502:physiology; D030762:Estrous Cycle / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006064:Gonadotropins, Equine / Q000494:pharmacology; D007247:Infertility, Female / Q000235:genetics / Q000503:physiopathology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000235:genetics; D010053:Ovary / Q000378:metabolism* / Q000648:ultrastructure; D010060:Ovulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D011247:Pregnancy; D011388:Prolactin / Q000502:physiology*; D011974:Receptors, LH / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D011981:Receptors, Prolactin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D013480:Superovulation / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: C486196:Ccnd2 protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D006063:Chorionic Gonadotropin; D056742:Cyclin D2; D016213:Cyclins; D006064:Gonadotropins, Equine; D018972:Insulin-Like Growth Factor Binding Protein 3; D011974:Receptors, LH; D011981:Receptors, Prolactin; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011388:Prolactin; D015096:3-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D002786:Cholesterol Side-Chain Cleavage Enzyme