Disease relevance of Gnrhr

• In the present study, we have expressed the rat GnRH receptor (GnRH-R) in insect cells, by infection with a recombinant baculovirus [1].
• This suggests that hyperprolactinemia inhibits GnRH-R responses to GnRH in females by a direct action on the pituitary gonadotroph [2].
• Expression of gonadotropin-releasing hormone receptor mRNA in the rat ventral prostate and dunning R3327 PAP adenocarcinoma before and after castration [3].
• This view, supported almost entirely by studies using the HA-tag (hemagglutinin influenza virus epitope tag) and other epitope and chimeric tags, obscured recognition that GnRHR mutants frequently become misrouted proteins [4].
• The GnRH receptor is a member of the ubiquitous seven-transmembrane segment G-protein-coupled receptor class and is the target of drug development for treatment of breast and prostate cancer, regulation of fertility, endometriosis and a range of other medical and veterinary uses [5].

Psychiatry related information on Gnrhr

• All animals were killed during the critical period (1400-1600 h), and GnRH receptor was assayed [6].

High impact information on Gnrhr

• The prolonged in vivo inhibition of pituitary GnRH receptor binding and luteinizing hormone secretion by the GnRH antagonist may be mediated by the slower dissociation rate of the antagonist from its specific pituitary membrane receptor site [7].
• These findings suggest that an agonist concentration-dependent switch in coupling of the GnRH-R between specific G proteins modulates neuronal Ca(2+) signaling via G(s)-cAMP stimulatory and G(i)-cAMP inhibitory mechanisms [8].
• We have overcome this limitation by transfecting the rat pituitary GH3 cell line with rat GnRH receptor (GnRHR) cDNA driven by a heterologous promoter [9].
• Taken together, these results indicate that the GnRH receptor activates both G(q) and G(s) signaling to regulate gene expression in L beta T2 cells [10].
• In contrast to other GPCRs, the GnRH-R does not show rapid desensitization of total inositol (IP) production, and the rates of internalization are exceptionally slow [11].

Chemical compound and disease context of Gnrhr

• Chronic hyperprolactinemia in intact rats decreased the pituitary GnRH receptor content, in addition to decreasing the mean LH concentrations during pulsatile GnRH administration [12].

Biological context of Gnrhr

• Three different rat GnRH-R cDNA stop codon mutations (one for each reading frame) were also made [11].
• We studied the expression patterns of GnRH and GnRH receptor (GnRH-R) in the same animals throughout the estrous cycle using real-time PCR [13].
• No significant changes in the level of hypothalamic GnRH-R mRNA were detected, although fluctuations during the day of proestrus are evident [13].
• Pituitary GnRH-R displayed a similar pattern of expression, except on estrus, when its mRNA levels declined [13].
• A reduction of GnRH-R is part of the mechanism of down-regulation of LH secretion by fast or slow GnRH frequencies, but altered frequency also exerts effects on secretory mechanisms at a site distal to the GnRH receptor [14].

Anatomical context of Gnrhr

• These structures were selected for this study because of their predicted ability to permeate the cell membrane and interact with a defined affinity with the GnRH receptor [15].
• Negative regulation of gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor gene expression by a gonadotrophin-releasing hormone agonist in the rat hypothalamus [16].
• The amounts of GnRH and GnRHR mRNA were measured in the preoptic area (POA) and posterior mediobasal hypothalamus (pMBH) micropunch samples from individual rat brain slices by respective competitive reverse transcription-polymerase chain reactions [16].
• Different primer pairs designed to amplify regions of mRNA encompassing the complete open reading frame plus a large part of the 3'-untranslated region revealed the presence of GnRH receptor transcripts of strictly identical nucleotide sequence in both pituitary and gonads, predicting a unique primary structure for the receptor protein [17].
• Recent in vivo studies reported that an application of gonadal steroids to gonadectomized animals modulated GnRH-R mRNA expression in the pituitary gland [18].

Associations of Gnrhr with chemical compounds

• A Glu/Asp7.32 residue in the extracellular loop 3 of the mammalian GnRH receptor (GnRHR) is known to interact with Arg8 of mammalian GnRH (mGnRH), which may confer preferential ligand selectivity for mGnRH than for chicken GnRH-II (cGnRH-II) [19].
• In presence of GnRH, GnRH-R expressing cells elicited a time- and dose-dependent production of inositol trisphosphate, with a maximum level reached within 30 min and an EC50 = 5 nM [1].
• Therefore, we assessed the effects of estrogen and progesterone on GnRH-R mRNA expression in primary cultured female rat pituitary cells [18].
• We further assessed the effects of GnRH on the turnover rate of GnRH-R mRNA using actinomycin D (2 microM) [20].
• Protein kinase C-mediated gonadotropin-releasing hormone receptor sequestration is associated with uncoupling of phosphoinositide hydrolysis [21].

Physical interactions of Gnrhr

• Pituitary GnRH-receptor content was assessed by the evaluation of saturation binding of a GnRH analog, [125I]-D-Ala6-des-Gly10-GnRH, to pituitary membrane preparations [22].
• These cell lines are good models for understanding the mechanisms by which the GnRH receptor is coupled to second messenger systems and for comparing these mechanisms with TRH-receptor coupling in the same cell [23].
• We have developed chimeric GnRHR-LHR that contain the full GnRHR coupled to various forms of the LH receptor C-terminus to explore the role of the LH receptor C-terminus in raft localization of the receptor and signaling [24].
• Stable transfection of GH3 cells with rat gonadotropin-releasing hormone receptor complementary deoxyribonucleic acid results in expression of a receptor coupled to cyclic adenosine 3',5'-monophosphate-dependent prolactin release via a G-protein [25].

Regulatory relationships of Gnrhr

• In the presence of transcription inhibitor, GnRH-induced augmentation of GnRH-R mRNA levels was completely abolished [20].
• We have proposed a model for GnRH self-priming that requires cross-communication between a GnRH receptor-activated protein kinase A pathway and the progesterone receptor (PR) to achieve amplification of the GnRH signal [26].
• Moreover, galanin also up-regulated GnRH receptor functional parameters (affinity and maximum binding capacity) but was ineffective in potentiating GnRH-induced accumulation of both subunit mRNAs [27].
• We previously reported that a blockade of GnRH receptor activation inhibited the already-initiated C-kinase pathway(s) [28].

Other interactions of Gnrhr

• Coupling of the agonist-activated GnRH-R to both G(s) and G(i) proteins was demonstrated by the ability of nanomolar GnRH concentrations to reduce membrane-associated alpha(s) and alpha(i3) levels and of higher concentrations to diminish alpha(i3) levels [8].
• The beta-arrestin-promoted increase in the k(e) value was diminished by cotransfecting cells with the dominant negative beta-arrestin-(319-418) mutant, whereas WT GnRH-R and stop codon mutant internalization were unaffected [29].
• This study examined the mechanism underlying the rat GnRH receptor (GnRH-R) internalization pathway by investigating the role of added/extended C-terminal tails and the effect of beta-arrestins and dynamin [29].
• Castration induced a 3.8-fold elevation in the amounts of GnRH-R mRNA after 3 weeks, whereas alpha, LH beta, and FSH beta mRNAs increased by 6.2-, 7.9-, and 4.2-fold, respectively, compared to corresponding values in intact animals [30].
• Similarly, administration of ovine PRL (during the first 48 h) to bromocriptine-treated rats produced low GnRH-R concentrations at 72 h [31].

Analytical, diagnostic and therapeutic context of Gnrhr

• Although a twofold increase in pituitary GnRH receptor content was observed at 28 days following the castration of control rats, GnRH receptor content in the pituitaries of PCO rats, at 28 days following ovariectomy, remained unchanged [22].
• METHODS: Immunohistochemical ABC methods and in situ hybridization methods were used to dectect protein and mRNA expression of GnRH receptor in GSMC, respectively [32].
• Using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), pituitary GnRH receptor mRNA levels were measured at various timepoints throughout the rat estrous cycle [33].
• Analyses of the regulation of GnRHR mRNA levels in the rat pituitary in vivo revealed a progressive increase in levels to 2.0 +/- 0.2-fold after ovariectomy (OVX) and 5.2 +/- 1.3-fold after castration (CAST) (21 days post-operative), compared to intact adult female and male controls, respectively [34].
• Northern blot analysis detected 3 species (5.0, 4.5 and 1.4 kb) of GnRH receptor mRNA in pituitary tissues [35].

References