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Submitted on July 15, 2003
Accepted on October 21, 2003
1 Signalisation Cellulaire, Régulation de Gènes et Physiologie de l'Axe Gonadotrope, CNRS UMR 7079, Physiologie et Physiopathologie, Université Pierre et Marie Curie, 4 place Jussieu, 75252 Paris cedex 05, France
* To whom correspondence should be addressed. E-mail: jean-noel.laverriere{at}snv.jussieu.fr.
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 (SF-1), activator protein 1 (AP-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 have 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 LH
and/or FSH subunit, but not in TSH 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 
-subunit at E13.5 and with that of SF-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.
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