In higher vertebrates, the main population of forebrain GnRH1 neurons originate in the embryonic olfactory placode. Early migration of GnRH neurons in mice - from the nasal placode into the nasal mesenchyme - depends on NELF (nasal embryonic LHRH factor). Furthermore, migratory GnRH cells express the leptin receptor. The precise role(s) of leptin during neuroendocrine GnRH development are unknown but it may combine with Neuropeptide Y (NPY) to regulate pulsatile GnRH1 levels at reproductive onset.
The aim was to find if NELF, Leptin receptor and NPY/NPY-receptor were also expressed in human GnRH1 olfactory neuroepithelial cells (FNC-B4).
Methods and Results
RNA was isolated from FNC-B4 cells and reverse transcribed. GAPDH, GnRH1, GnRH1-Receptor, Leptin receptor (ObR), NPY and NPY-receptor were amplified by PCR and GnRH1 was found, along with a truncated GnRH1-receptor transcript. NPY-R1/R2 receptor subtypes were detected, but not NPY. 3 variants of the leptin receptor were also found: HuOb-R (full-length receptor), HuB219.2 and HuB219.3. PCR primers for NELF were based on homology with the mouse cDNA and ESTs on the human genome databases. 1 of 2 predicted NELF splice variants were detected in FNC-B4 cells by RT-PCR, and these map to a locus on chromosome 9.
Discussion and conclusions
In the post-natal hypothalmus, NPY-immunoreactive afferents provide a synaptic input into GnRH neurons and are thought to act as a 'brake' on GnRH release. Leptin is also thought to act as an important regulator for the reproductive neuroendocrine axis and we have shown that 3 leptin receptor isoforms, and 2 NPY receptor isoforms are expressed in FNC-B4 cells. Furthermore, the expression of NELF by the FNC-B4 clone is consistent with these cells having a migratory phenotype. These results suggest that some of the signalling pathways, which function in differentiated GnRH neurons, may also be active in migratory GnRH neurons.
03 - 04 Dec 2001
Society for Endocrinology