Abstract
Neuropeptide Y (NPY) regulates reproductive function at the level of the hypothalamus through control of GnRH secretion. However, the direct control of GnRH gene expression by NPY has not yet been studied. GT1-7 neurons were treated with 100 nM of NPY over a 36 h time course. GnRH mRNA levels were significantly increased by NPY up to 12 h. We determined that GT1-7 neurons expressed Y1, Y2, and Y4 NPY receptors, but not Y5. Functional analysis of NPY receptor activation indicated that the Y1/Y4/Y5 receptor agonist [Leu31, Pro34] significantly induced cAMP accumulation in the GT1-7 neurons. Western blot studies demonstrated changes in the phosphorylation status of AKT, ERK1/2, CREB and ATF-1 after NPY exposure. Pharmacological inhibitors of the MAPK and PKA signal transduction pathways attenuated the NPY-mediated increase in GnRH transcription. This NPY-mediated increase in GnRH mRNA was also inhibited with the Y1-receptor specific antagonist BIBP-3226. The mHypoE-38 neurons secrete detectable levels of NPY and can be used as an endogenous source of NPY. Conditioned medium from mHypoE-38 neurons induced an increase in GnRH mRNA, which was inhibited by the Y1 receptor antagonist BIBP-3226. Together, these studies strengthen the evidence for the importance of NPY in the regulation of reproductive function.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.