Abstract
Stimulation of pituitary gonadotropes expressing the Gq/ 11-coupled gonadotropin releasing hormone (GnRH) and muscarinic M3 acetylcholine receptors with GnRH or carbachol upregulates the biosynthesis of the zinc finger transcription factor Egr-1. Receptor stimulation activates phospholipase C, leading to elevated cytosolic Ca2+ levels following stimulation. Accordingly, GnRHand carbachol-triggered biosynthesis of Egr-1 was blocked by BAPTA-AM, an intracellular calcium chelator. Ca2+-mediated activation of extracellular signal-regulated protein kinase (ERK) was accomplished via activation of protein kinase C and transactivation of the EGF receptor. Calmodulin was also required to connect GnRH and carbachol signaling with the upregulation of Egr-1 gene transcription. Lentiviral-mediated expression of a dominant-negative mutant of Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, impaired GnRHand carbachol-induced biosynthesis of Egr-1. Thus, Elk-1 connects the GnRHand carbacholinduced signaling cascades in the nucleus with the Egr-1 gene. Lentiviral-mediated expression of MAP kinase phosphatase-1 (MKP-1), the enzyme that dephosphorylates and inactivates ERK, completely blocked Egr-1 biosynthesis following GnRH or carbachol stimulation, indicating that MKP-1 functions as a nuclear shut-of-device of these signaling pathways. Chromatin immunoprecipitation experiments revealed that Egr-1 bound in vivo to the regulatory regions of the basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGFbeta) genes following stimulation of the cells with GnRH or carbachol. As a result, elevated levels of bFGF and TGFbeta mRNA were detected in GnRH and carbachol stimulated gonadotropes, corroborating the view that Egr-1 transactivates the bFGF and TGFbeta genes following stimulation of the cells with GnRH or carbachol. from Annual Meeting of the Study Group Neurochemistry. International Conference of the Gesellschaft fur Biochemie und Molekularbiologie 2006 (GBM 2006): Molecular pathways in health and disease of the nervous system Witten, Germany. 28–30 September 2006
Highlights
Stimulation of pituitary gonadotropes expressing the Gq/ 11-coupled gonadotropin releasing hormone (GnRH) and muscarinic M3 acetylcholine receptors with GnRH or carbachol upregulates the biosynthesis of the zinc finger transcription factor Egr-1
GnRH- and carbachol-triggered biosynthesis of Egr-1 was blocked by BAPTA-AM, an intracellular calcium chelator
Calmodulin was required to connect GnRH and carbachol signaling with the upregulation of Egr-1 gene transcription
Summary
Stimulation of pituitary gonadotropes expressing the Gq/ 11-coupled gonadotropin releasing hormone (GnRH) and muscarinic M3 acetylcholine receptors with GnRH or carbachol upregulates the biosynthesis of the zinc finger transcription factor Egr-1. Upregulation of Egr-1 biosynthesis in pituitary gonadotropes following activation of GnRH and muscarinic acetylcholine receptors Address: University of Saarland, Department of Medical Biochemistry and Molecular Biology, Homburg, Germany * Corresponding author from Annual Meeting of the Study Group Neurochemistry.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: 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.
