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Involvement of the Ser‐Glu‐Pro Motif in Ligand Species‐Dependent Desensitisation of the Rat Gonadotrophin‐Releasing Hormone Receptor
Author(s) -
Song J. A.,
Oh D. Y.,
Moon J. S.,
Geum D.,
Kwon H. B.,
Seong J. Y.
Publication year - 2006
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2006.01469.x
Subject(s) - gnrhr , gonadotropin releasing hormone , gonadotropin releasing hormone receptor , medicine , receptor , endocrinology , biology , mutant , thyrotropin releasing hormone receptor , extracellular , chemistry , inositol phosphate , hormone , microbiology and biotechnology , inositol , hormone receptor , gene , luteinizing hormone , biochemistry , breast cancer , cancer
There are two forms of gonadotrophin‐releasing hormone (GnRH), GnRH‐I and GnRH‐II, in the vertebrate brain. Both GnRH‐I and GnRH‐II are thought to interact with the type‐I GnRH receptor (GnRHR). The present study attempted to demonstrate whether GnRH‐I and GnRH‐II induce differential desensitisation of GnRHR and to identify the motif involved. Time course inositol phosphate (IP) accumulation assay reveals that, in cells expressing the wild‐type rat GnRHR, GnRH‐I induced continuous increase in IP production, whereas GnRH‐II‐induced IP production rate at later time points (30–120 min after ligand treatment) became attenuated. However, in cells expressing the mutant receptor in which the Ser‐Glu‐Pro (SEP) motif in extracellular loop 3 was replaced by Pro‐Glu‐Val (PEV), IP accumulation rates at later time points were more decreased by GnRH‐I than GnRH‐II. Ca 2+ responses to repetitive GnRH applications reveal that GnRH‐II desensitised the wild‐type receptor faster than GnRH‐I, whereas the opposite situation was observed in the PEV mutant. In addition, cell surface loss of GFP‐tagged wild‐type receptor was more facilitated by GnRH‐II than GnRH‐I, whereas that of the GFP‐tagged PEV mutant receptor was more enhanced by GnRH‐I than GnRH‐II. The present study indicates that the SEP motif is potentially responsible for ligand species–dependent receptor desensitisation. Together, these results suggest that GnRH‐I and GnRH‐II may have different effects on mammalian type‐I GnRHR via modulation of desensitisation rates.