Oral Presentation The International Congress of Neuroendocrinology 2014

Inside and outside the pituitary: developmental and functional analysis of GnRH receptor gene expression (#39)

Anne-Laure Schang 1 2 , Raymond Counis 1 3 4 , Joelle Cohen-Tannoudji 1 3 4 , Jean-Noel Laverriere 1 3 4
  1. Université Paris Diderot Paris 7, Paris, France
  2. U1141 PROTECT, Inserm, Paris, France
  3. U1133, Inserm, Paris, France
  4. U8251 BFA, CNRS, Paris, France

The GnRH receptor (GnRHR) plays a central role in the neuroendocrine control of reproductive function with its expression restricted to gonadotrope cells in the pituitary. To elucidate the mechanisms involved in rat GnRHR gene (Gnrhr) specific expression, we have analyzed the combinatorial code of transcription factors that modulates promoter activity in gonadotrope cells. Within the distal promoter, a bifunctional element regulated transcriptional activity both positively and negatively through LIM homeodomain proteins (ISL1 and LHX3) and GATA2, respectively. Besides, in the proximal promoter, two TAAT motifs conferred response to Paired-like factors PROP1 and OTX2. Importantly, these transcription factors are expressed during pituitary ontogenesis and therefore may participate in the onset of Gnrhr expression that occurs around embryonic day 13.5 in the developing pituitary.

However, Gnrhr expression is far to be restricted to the pituitary, being notably described in the hippocampus, where its function remains unclear. We showed that the onset of Gnrhr expression occurred during postnatal development in the rat hippocampus, contrasting with the pituitary. Using a transgenic mouse model that expresses the human placental alkaline phosphatase reporter gene under the control of the 3.3 kb rat Gnrhr promoter (Gnrhr-ALPP), we confirmed that Gnrhr promoter was activated postnatally. Transgene expression was further localized in a subpopulation of hippocampal neurons and could be observed along hippocampal-septal projections. Additional in vitro analyzes suggested that GnRHR modulated synaptic plasticity. Furthermore, using Gnrhr-ALPP mice, we uncovered two novel sites of Gnrhr expression in mammals, the retina and the pineal gland, suggesting that GnRHR is involved in synchronization of biological rhythms.

Altogether, these data highlight questions regarding the functional importance of this receptor and its ligand and could contribute to determine how and when the GnRHR is expressed specifically in these organs and to what extent these expressions are related to the reproductive function.