title: Prolactin receptors and placental lactogen drive male mouse pancreatic islets to pregnancy-related mRNA changes.
abstract: Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified prolactin receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express prolactin receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by stimulating cultured islets with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression pattern of pregnant prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or when transplanted in female recipients that became pregnant (day 12.5), male islets induced the 'islet pregnancy gene signature', which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity and beta cell proliferation was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to further investigate the importance of prolactin receptors in these mRNA changes we used a prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in both male and female beta cells.
authors: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors: Lotte
authors: L
authors: Goyvaerts
authors: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors: Katleen
authors: K
authors: Lemaire
authors: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; Department of Clinical and Experimental Medicine, Translational Research Center for Gastrointestinal Disorders (TARGID), University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium.
authors: Ingrid
authors: I
authors: Arijs
authors: Inserm U693, Faculté de Médecine Paris-Sud, Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors: Julien
authors: J
authors: Auffret
authors: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors: Mikaela
authors: M
authors: Granvik
authors: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors: Leentje
authors: L
authors: Van Lommel
authors: Inserm U693, Faculté de Médecine Paris-Sud, Université Paris-Sud, Le Kremlin-Bicêtre, France.
authors: Nadine
authors: N
authors: Binart
authors: Department of Pathology, Vrije Universiteit Brussel, Jette, Belgium.
authors: Peter
authors: P
authors: in't Veld
authors: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors: Frans
authors: F
authors: Schuit
authors: Gene Expression Unit, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
authors: Anica
authors: A
authors: Schraenen
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D008297:Male; D051379:Mice; D010928:Placental Lactogen / Q000097:blood* / Q000494:pharmacology; D011247:Pregnancy / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D011981:Receptors, Prolactin; D010928:Placental Lactogen