Abstract
BackgroundLuteinizing hormone secreted by the anterior pituitary gland regulates gonadal function. Luteinizing hormone secretion is regulated both by alterations in gonadotrope responsiveness to hypothalamic gonadotropin releasing hormone and by alterations in gonadotropin releasing hormone secretion. The mechanisms that determine gonadotrope responsiveness are unknown but may involve regulators of G protein signaling (RGSs). These proteins act by antagonizing or abbreviating interaction of Gα proteins with effectors such as phospholipase Cβ. Previously, we reported that gonadotropin releasing hormone-stimulated second messenger inositol trisphosphate production was inhibited when RGS3 and gonadotropin releasing hormone receptor cDNAs were co-transfected into the COS cell line. Here, we present evidence for RGS3 inhibition of gonadotropin releasing hormone-induced luteinizing hormone secretion from cultured rat pituitary cells.ResultsA truncated version of RGS3 (RGS3T = RGS3 314–519) inhibited gonadotropin releasing hormone-stimulated inositol trisphosphate production more potently than did RSG3 in gonadotropin releasing hormone receptor-bearing COS cells. An RSG3/glutathione-S-transferase fusion protein bound more 35S-Gqα than any other member of the G protein family tested. Adenoviral-mediated RGS3 gene transfer in pituitary gonadotropes inhibited gonadotropin releasing hormone-stimulated luteinizing hormone secretion in a dose-related fashion. Adeno-RGS3 also inhibited gonadotropin releasing hormone stimulated 3H-inositol phosphate accumulation, consistent with a molecular site of action at the Gqα protein.ConclusionsRGS3 inhibits gonadotropin releasing hormone-stimulated second messenger production (inositol trisphosphate) as well as luteinizing hormone secretion from rat pituitary gonadotropes apparently by binding and suppressing the transduction properties of Gqα protein function. A version of RGS3 that is amino-terminally truncated is even more potent than intact RGS3 at inhibiting gonadotropin releasing hormone-stimulated inositol trisphosphate production.
Highlights
Luteinizing hormone secreted by the anterior pituitary gland regulates gonadal function
The initial experiments were performed to confirm our earlier finding that RGS3 suppressed GnRH-stimulated IP3 production in COS-1 cells [9] and to test a truncated form of RGS3, RGS3T (RGS3 314–519) [24] for suppressive activity in the same assay (Fig. 1). cDNAs representing the GnRH receptor and RGS3 or RGS3T were cotransfected into COS-1 cells for GnRH-A treatment 72 h later; intracellular IP3 concentrations were measured at
Identification of a C-terminal 205 amino acid variant of RGS3 that has equal or greater potency than the full-length 519 amino acid RGS3 will facilitate the identification of RGS3 functional protein domains that are important for its activity
Summary
Luteinizing hormone secreted by the anterior pituitary gland regulates gonadal function. The mechanisms that determine gonadotrope responsiveness are unknown but may involve regulators of G protein signaling (RGSs) These proteins act by antagonizing or abbreviating interaction of Gα proteins with effectors such as phospholipase Cβ. A near-universal feature of cell signaling via seven transmembrane, G protein-coupled receptors is attenuation of a cellular response upon prolonged exposure to an extracellular stimulus [1] This desensitization process is well-established for GnRH-stimulated LH secretion from pituitary gonadotropes [2,3], and occurs after about 6 h of continued exposure to GnRH in rats [3]; removal of GnRH permits recovery from the profound suppression of LH secretion, albeit rather slowly (2–4 days; 4). RGS proteins have been described that interact with the Giα and Gqα members of the G protein family [17,18,19,20,21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
