The promoter of the rat gonadotropin-releasing hormone receptor gene directs the expression of the human placental alkaline phosphatase reporter gene in gonadotrope cells in the anterior pituitary gland as well as in multiple extrapituitary tissues.
Previous studies dealing with the mechanisms underlying the tissue-specific and regulated expression of the GnRH receptor (GnRH-R) gene led us to define several cis-acting regulatory sequences in the rat GnRH-R gene promoter. These include functional sites for steroidogenic factor 1, activator protein 1, and motifs related to GATA and LIM homeodomain response elements as demonstrated primarily in transient transfection assays in mouse gonadotrope-derived cell lines. To understand these mechanisms in more depth, we generated transgenic mice bearing the 3.3-kb rat GnRH-R promoter linked to the human placental alkaline phosphatase reporter gene. Here we show that the rat GnRH-R promoter drives the expression of the reporter gene in pituitary cells expressing the LHbeta and/or FSHbeta subunit but not in TSHbeta- or GH-positive cells. Furthermore, the spatial and temporal pattern of the transgene expression during the development of the pituitary was compatible with that characterizing the emergence of the gonadotrope lineage. In particular, transgene expression is colocalized with the expression of the glycoprotein hormone alpha-subunit at embryonic day 13.5 and with that of steroidogenic factor 1 at later stages of pituitary development. Transgene expression was also found in specific brain areas, such as the lateral septum and the hippocampus. A single promoter is thus capable of directing transcription in highly diverse tissues, raising the question of the different combinations of transcription factors that lead to such a multiple, but nevertheless cell-specific, expressions of the GnRH-R gene.
Centre National de la Recherche Scientifique Unité Mixte de Recherche 7079, Physiologie et Physiopathologie, Université Pierre et Marie Curie, 4 place Jussieu, Case courrier 256, 75252 Paris cedex 05, France.
Anne
A
Granger
Valérie
V
Ngô-Muller
Christian
C
Bleux
Céline
C
Guigon
Hanna
H
Pincas
Solange
S
Magre
Dominique
D
Daegelen
Andrée
A
Tixier-Vidal
Raymond
R
Counis
Jean-Noël
JN
Laverrière
D000469:Alkaline Phosphatase / Q000235:genetics*; D000818:Animals; D001923:Brain Chemistry; D005260:Female; D037201:Follicle Stimulating Hormone, beta Subunit / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics*; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006651:Histocytochemistry; D006801:Humans; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010903:Pituitary Gland, Anterior / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid
D037201:Follicle Stimulating Hormone, beta Subunit; D037101:Luteinizing Hormone, beta Subunit; D011993:Recombinant Fusion Proteins; D007987:Gonadotropin-Releasing Hormone; D000469:Alkaline Phosphatase