title: Rat Gnrhr promoter directs species-specific gene expression in the pituitary and testes of transgenic mice.
abstract: The GnRH receptor (GnRHR) is expressed in several non-pituitary tissues, notably in gonads. However, mechanisms underlying the gonad-specific expression of Gnrhr are not well understood. Here, Gnrhr expression was analysed in the developing testes and pituitaries of rats and transgenic mice bearing the human placental alkaline phosphatase reporter gene (ALPP) under the control of the rat Gnrhr promoter. We showed that the 3.3 kb, but not the pituitary-specific 1.1 kb promoter, directs ALPP expression exclusively to testis Leydig cells from embryonic day 12 onwards. Real-time PCR analysis revealed that promoter activity displayed the same biphasic profile as marker genes in Leydig cells, i.e. abrupt declines after birth followed by progressive rises after a latency phase, in coherence with the differentiation and evolution of foetal and adult Leydig cell lineages. Interestingly, the developmental profile of transgene expression showed high similarity with the endogenous Gnrhr profile in the rat testis, while mouse Gnrhr was only poorly expressed in the mouse testis. In the pituitary, both transgene and Gnrhr were co-expressed at measurable levels with similar ontogenetic profiles, which were markedly distinct from those in the testis. Castration that induced pituitary Gnrhr up-regulation in rats did not affect the mouse Gnrhr. However, it duly up-regulated the transgene. In addition, in LβT2 cells, the rat, but not mouse, Gnrhr promoter was sensitive to GnRH agonist stimulation. Collectively, our data highlight inter-species variations in the expression and regulation of Gnrhr in two different organs and reveal that the rat promoter sequence contains relevant genetic information that dictates rat-specific gene expression in the mouse context.
authors.affiliation: Université Paris Diderot Paris 7, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative, EAC CNRS 4413, Physiologie de l'Axe Gonadotrope, Bâtiment Buffon, case courier 7007, 4, rue MA Lagroua Weill-Hallé, 75205 Paris cedex 13, France.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ishaq
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Schang
authors.forename: Solange
authors.initials: S
authors.lastname: Magre
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Laverrière
authors.forename: Aurélien
authors.initials: A
authors.lastname: Guillou
authors.forename: Noëlline
authors.initials: N
authors.lastname: Coudouel
authors.forename: Richard
authors.initials: R
authors.lastname: Wargnier
authors.forename: Joëlle
authors.initials: J
authors.lastname: Cohen-Tannoudji
authors.forename: Raymond
authors.initials: R
authors.lastname: Counis
mesh_terms: D000818:Animals; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D055647:Rats, Transgenic; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*
chemical_list: D011966:Receptors, LHRH