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Oregon Regional Primate Research Center (X.L., J.A.J., S.B.,
P.M.C.) Beaverton, Oregon 97006
Department of Physiology
and Pharmacology (P.M.C.) Oregon Health Sciences University
Portland, Oregon 97201
Research Group for Comparative
Endocrinology (M.B., J.B.) University of Utrecht 3584 CH
Utrecht, The Netherlands
Mammalian GnRH receptor (GnRHR) is unique among G protein-coupled seven-transmembrane segment receptors due to the absence of an intracellular C-terminal tail frequently important for internalization and/or desensitization of other G protein-coupled receptors. The recent cloning of nonmammalian (i.e. catfish, goldfish, frog, and chicken) GnRHRs shows that these contain an intracellular C terminus. Addition of the 51-amino acid intracellular C terminus from catfish GnRHR (cfGnRHR) to rat GnRHR (rGnRHR) did not affect rGnRHR binding affinity but elevated receptor expression by about 5-fold. Truncation of the added C terminus impaired the elevated receptor-binding sites by 3- to 8-fold, depending on the truncation site. In addition, introducing the C terminus to rGnRHR altered the pattern of receptor regulation from biphasic down-regulation and recovery to monophasic down-regulation. The extent of down-regulation was also enhanced. The alteration in receptor regulation due to the addition of a C terminus was reversed by truncation of the added C terminus. Furthermore, addition of the cfGnRHR C terminus to rGnRHR significantly augmented the inositol phospholipid (IP) response of transfected cells to Buserelin, but this did not result from the elevation of receptor-binding sites. Addition of the C terminus did not affect Buserelin-stimulated cAMP and PRL release. GH3 cells transfected with wild-type cfGnRHR did not show measurable Buserelin binding or significant stimulation of IP, cAMP, or PRL in response to Buserelin (10-13-10-9 M). GH3 cells transfected with C terminus-truncated cfGnRHR showed no IP response to Buserelin (10-13-10-7 M). These results suggest that addition of the cfGnRHR intracellular C terminus to rGnRHR has a significant impact on rGnRHR expression and regulation and efficiency of differential receptor coupling to G proteins.
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A. Cornea, J. A. Janovick, X. Lin, and P. M. Conn Simultaneous and Independent Visualization of the Gonadotropin-Releasing Hormone Receptor and Its Ligand: Evidence for Independent Processing and Recycling in Living Cells Endocrinology, September 1, 1999; 140(9): 4272 - 4280. [Abstract] [Full Text]
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G. Maya-Núñez and P. M. Conn Transcriptional Regulation of the Gonadotropin-Releasing Hormone Receptor Gene Is Mediated in Part by a Putative Repressor Element and by the Cyclic Adenosine 3',5'-Monophosphate Response Element Endocrinology, August 1, 1999; 140(8): 3452 - 3458. [Abstract] [Full Text]
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X.-b. Han and P. M. Conn The Role of Protein Kinases A and C Pathways in the Regulation of Mitogen-Activated Protein Kinase Activation in Response to Gonadotropin-Releasing Hormone Receptor Activation Endocrinology, May 1, 1999; 140(5): 2241 - 2251. [Abstract] [Full Text]
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 N. Illing, B. E. Troskie, C. S. Nahorniak, J. P. Hapgood, R. E. Peter, and R. P. Millar Two gonadotropin-releasing hormone receptor subtypes with distinct ligand selectivity and differential distribution in brain and pituitary in the goldfish (Carassius auratus) PNAS, March 2, 1999; 96(5): 2526 - 2531. [Abstract] [Full Text] [PDF]
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X. Lin and P. M. Conn Transcriptional Activation of Gonadotropin-Releasing Hormone (GnRH) Receptor Gene by GnRH: Involvement of Multiple Signal Transduction Pathways Endocrinology, January 1, 1999; 140(1): 358 - 364. [Abstract] [Full Text]
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X. Lin, J. A. Janovick, and P. M. Conn Mutations at the Consensus Phosphorylation Sites in the Third Intracellular Loop of the Rat Gonadotropin-Releasing Hormone Receptor: Effects on Receptor Ligand Binding and Signal Transduction Biol Reprod, December 1, 1998; 59(6): 1470 - 1476. [Abstract] [Full Text]
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X. Lin and P. M. Conn Transcriptional Activation of Gonadotropin-Releasing Hormone (GnRH) Receptor Gene by GnRH and Cyclic Adenosine Monophosphate Endocrinology, September 1, 1998; 139(9): 3896 - 3902. [Abstract] [Full Text] [PDF]
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A. Ulloa-Aguirre, D. Stanislaus, V. Arora, J. Vaananen, S. Brothers, J. A. Janovick, and P. M. Conn The Third Intracellular Loop of the Rat Gonadotropin-Releasing Hormone Receptor Couples the Receptor to Gs- and Gq/11-Mediated Signal Transduction Pathways: Evidence from Loop Fragment Transfection in GGH3 Cells Endocrinology, May 1, 1998; 139(5): 2472 - 2478. [Abstract] [Full Text] [PDF]
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Y.-M. Sun, C. A. Flanagan, N. Illing, T. R. Ott, R. Sellar, B. J. Fromme, J. Hapgood, P. Sharp, S. C. Sealfon, and R. P. Millar A Chicken Gonadotropin-releasing Hormone Receptor That Confers Agonist Activity to Mammalian Antagonists. IDENTIFICATION OF D-LYS6 IN THE LIGAND AND EXTRACELLULAR LOOP TWO OF THE RECEPTOR AS DETERMINANTS J. Biol. Chem., March 9, 2001; 276(11): 7754 - 7761. [Abstract] [Full Text] [PDF]
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