LHRH PULSE GENERATION AND STEROID FEEDBACK

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To understand the mechanism of LHRH pulse generation and the mechanism of steroid action on LHRH neurons. Pulsatile release of LHRH from the hypothalamus is essential for normal reproductive function, yet the mechanism of LHRH pulse generation is unclear. We cultured LHRH neurons originating from the olfactory pit/placode region and characterized the cellular mechanism of LHRH pulse generation. The periodicity of peptide release and bursting activity of LHRH neurons were much slower than mouse LHRH neurons, although many characteristics in monkey LHRH neurons are similar to those described for mice. The aim of this study is to understand the mechanism of LHRH pulse generation and the mechanism of steroid action on LHRH neurons. Recently, we found that LHRH neurons respond to estradiol with a short latency (within a minute), stimulating the frequency of firing activity and intracellular calcium oscillations, and LHRH release. This rapid action of estradiol appears to be, in part, mediated by the 7-transmembrane receptor, GPR30, as LHRH neurons treated with siRNA for GPR30 do not respond to estradiol, and the GPR30 agonist G1 causes a response similar to estradiol. Moreover, the rapid action of estradiol through GPR30 is dissimilar to the rapid action caused by the synthetic estrogenic substance, STX. These exciting findings are extremely important for the development of contraceptive tools and treatment of infertility. This research used WNPRC Animal Services and Assay Services. PUBLICATIONS: Noel, S.D., Keen, K.L., Baumann, D.I., Filardo, E.J., and Terasawa, E. Involvement of G-protein coupled receptor 30 (GPR30) in rapid action of estrogen in primate LHRH neurons. Mol. Endocrinol. 23: 349-359, 2009. PMID: 19131510 Terasawa, E., Noel, S.D., and Keen, K.L. Rapid action of estrogen in LHRH neurons: The role of GPR30. J. Neuroendocrinol. 21: 316-321, 2009. PMID: 19207808