GnRH receptor gene expression in the developing rat hippocampus: transcriptional regulation and potential roles in neuronal plasticity.
In the pituitary of mammals, the GnRH receptor (GnRHR) plays a primary role in the control of reproductive function. It is further expressed in the hippocampus, where its function, however, is not well defined. By quantitative RT-PCR analyses, we demonstrate herein that the onset of GnRHR gene (Gnrhr) expression in the rat hippocampus was unexpectedly delayed as compared to the pituitary and only occurred after birth. Using a previously described transgenic mouse model bearing the human placental alkaline phosphatase reporter gene under the control of the rat Gnrhr promoter, we established a positive correlation between the temporal pattern of Gnrhr mRNA levels and promoter activity in the hippocampal formation. The gradual appearance of human placental alkaline phosphatase transgene expression occurred simultaneously in the hippocampus and interconnected structures such as the lateral septum and the amygdala, coinciding with the establishment of hippocampo-septal projections. Analysis of transcription factors together with transient transfection assays in hippocampal neurons indicated that the combinatorial code governing the hippocampus-specific expression of the Gnrhr is distinct from the pituitary, likely involving transactivating factors such as NUR77, cyclic AMP response element binding protein, and Finkel-Biskis-Jinkins murine osteosarcoma virus oncogene homolog. A silencing transcription factor acting via the -3255/-1135 promoter region of the Gnrhr may be responsible for the transcriptional repression observed around birth. Finally, GnRH directly stimulated via activation of its receptor the expression of several marker genes of neuronal plasticity such as Egr1, synaptophysin, and spinophilin in hippocampal primary cultures, suggesting a role for GnRHR in neuronal plasticity. Further characterization of these mechanisms may help unravel important functions of GnRH/GnRHR signaling in the brain.
Université Paris-Diderot Paris 7, Equipe d'Accueil Conventionnée Centre National de la Recherche Scientifique 4413, Physiologie de l'Axe Gonadotrope, Bâtiment Buffon, 4 rue MA Lagroua Weill-Hallé 75205 Paris cedex 13, France.
Anne-Laure
AL
Schang
Valérie
V
Ngô-Muller
Christian
C
Bleux
Anne
A
Granger
Marie-Claude
MC
Chenut
Catherine
C
Loudes
Solange
S
Magre
Raymond
R
Counis
Joëlle
J
Cohen-Tannoudji
Jean-Noël
JN
Laverrière
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D011966:Receptors, LHRH / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016708:Synaptophysin / Q000235:genetics / Q000378:metabolism; D000099273:Neurabins
D000469:Alkaline Phosphatase; D051766:Early Growth Response Protein 1; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D011966:Receptors, LHRH; D016708:Synaptophysin; D000099273:Neurabins; C486110:Egr1 protein, rat