Potential regulatory roles for G protein-coupled receptor kinases and beta-arrestins in gonadotropin-releasing hormone receptor signaling

Endocrinology
J D NeillJ C Sellers

Abstract

GnRH stimulates gonadotropin secretion, which desensitizes unless the releasing hormone is secreted or administered in a pulsatile fashion. The mechanism of desensitization is unknown, but as the GnRH receptor is G protein coupled, it might involve G protein-coupled receptor kinases (GRKs). Such kinases phosphorylate the intracellular regions of seven-transmembrane receptors, permitting beta-arrestin to bind, which prevents the receptor from activating G proteins. Here, we tested the effect of GRKs and beta-arrestins on GnRH-induced inositol trisphosphate (IP3) production in COS cells transfected with the GnRH receptor complementary DNA. GRK2, -3, and -6 overexpression inhibited IP3 production by 50-75% during the 30 sec of GnRH treatment. Coexpression of GRK2 and beta-arrestin-2 suppressed GnRH-induced IP3 production more than that of either alone. Immunocytochemical staining of rat anterior pituitary revealed that all cells expressed GRK2, -3, and -6; all cells also expressed the beta-arrestins. Western blots on cytosolic extracts of rat pituitaries revealed the presence of GRK2/3 and beta-arrestin-1 and -2. The expression of GRKs and beta-arrestins by gonadotropes and their inhibition of GnRH-stimulated IP3 production in COS...Continue Reading

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Citations

Jan 9, 2013·Proceedings of the National Academy of Sciences of the United States of America·Vanessa L WehbiJean-Pierre Vilardaga
May 17, 2007·American Journal of Physiology. Endocrinology and Metabolism·Jie ZhouJosephine M Egan
May 5, 1999·The Journal of Physiology·M Bünemann, M M Hosey
Jan 30, 2018·Journal of Cellular and Molecular Medicine·Maria Caroline Alves CoelhoMônica R Gadelha
Feb 26, 2000·Acta Physiologica Scandinavica·U HoltbäckA Aperia
Aug 28, 1999·The Journal of Comparative Neurology·A Kittel, N Komori

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