title: Identification and analysis of two novel sites of rat GnRH receptor gene promoter activity: the pineal gland and retina.
abstract: OBJECTIVE
  In mammals, activation of pituitary GnRH receptor (GnRHR) by hypothalamic GnRH increases the synthesis and secretion of LH and FSH, which, in turn, regulate gonadal functions. However, GnRHR gene (Gnrhr) expression is not restricted to the pituitary.
  
  
  METHODS
  To gain insight into the extrapituitary expression of Gnrhr, a transgenic mouse model that expresses the human placental alkaline phosphatase reporter gene driven by the rat Gnrhr promoter was created.
  
  
  RESULTS
  This study shows that the rat Gnrhr promoter is operative in two functionally related organs, the pineal gland, as early as embryonic day (E) 13.5, and the retina where activity was only detected at E17.5. Accordingly, Gnrhr mRNA were present in both tissues. Transcription factors known to regulate Gnrhr promoter activity such as the LIM homeodomain factors LHX3 and ISL1 were also detected in the retina. Furthermore, transient transfection studies in CHO and gonadotrope cells revealed that OTX2, a major transcription factor in both pineal and retina cell differentiation, is able to activate the Gnrhr promoter together with either CREB or PROP1, depending on the cell context.
  
  
  CONCLUSIONS
  Rather than using alternate promoters, Gnrhr expression is directed to diverse cell lineages through specific associations of transcription factors acting on distinct response elements along the same promoter. These data open new avenues regarding GnRH-mediated control of seasonal and circadian rhythms in reproductive physiology.
authors.affiliation: Université Paris Diderot Paris 7, Sorbonne Paris Cité, Biologie Fonctionnelle et Adaptative, EAC CNRS 4413, Physiologie de l'Axe Gonadotrope, Paris, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Schang
authors.forename: Christian
authors.initials: C
authors.lastname: Bleux
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Chenut
authors.forename: Valérie
authors.initials: V
authors.lastname: Ngô-Muller
authors.forename: Bruno
authors.initials: B
authors.lastname: Quérat
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Jeanny
authors.forename: Raymond
authors.initials: R
authors.lastname: Counis
authors.forename: Joëlle
authors.initials: J
authors.lastname: Cohen-Tannoudji
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Laverrière
mesh_terms: D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004622:Embryo, Mammalian; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D010870:Pineal Gland / Q000196:embryology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011966:Receptors, LHRH / Q000235:genetics*; D012160:Retina / Q000196:embryology / Q000378:metabolism*
chemical_list: D011966:Receptors, LHRH