Molecular cloning and expression of cDNA encoding the murine gonadotropin-releasing hormone receptor.

Reinhart, John B.; Mertz, Lawrence M.; Catt, Kevin J.

doi:10.1016/s0021-9258(19)36602-5

Cited by 218 publications

(10 citation statements)

References 43 publications

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“…Some immortalized cell lines derived from neoplastic tissues also proved to be an important source of GnRH-R (747). One of them, the mouse pituitary ␣T3 gonadotrope cell line, led to the molecular isolation of the first GnRH receptor sequence, by expression screening for electrophysiological (809) or calcium responses (634) in Xenopus oocytes. This sequence provided the basis for the cloning of GnRH-R in several other species (506,686).…”

Section: Gnrh Receptors In Mammalsmentioning

confidence: 99%

Origin and Evolution of the Neuroendocrine Control of Reproduction in Vertebrates, With Special Focus on Genome and Gene Duplications

Dufour

Quérat

Tostivint

et al. 2020

Physiological Reviews

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In humans, as in the other mammals, the neuroendocrine control of reproduction is ensured by the brain-pituitary gonadotropic axis. Multiple internal and environmental cues are integrated via brain neuronal networks, ultimately leading to the modulation of the activity of gonadotropin-releasing hormone (GnRH) neurons. The decapeptide GnRH is released into the hypothalamic-hypophysial portal blood system and stimulates the production of pituitary glycoprotein hormones, the two gonadotropins luteinizing hormone and follicle-stimulating hormone. A novel actor, the neuropeptide kisspeptin, acting upstream of GnRH, has attracted increasing attention in recent years. Other neuropeptides, such as gonadotropin-inhibiting hormone/RF-amide related peptide, and other members of the RF-amide peptide superfamily, as well as various nonpeptidic neuromediators such as dopamine and serotonin also provide a large panel of stimulatory or inhibitory regulators. This paper addresses the origin and evolution of the vertebrate gonadotropic axis. Brain-pituitary neuroendocrine axes are typical of vertebrates, the pituitary gland, mediator and amplifier of brain control on peripheral organs, being a vertebrate innovation. The paper reviews, from molecular and functional perspectives, the evolution across vertebrate radiation of some key actors of the vertebrate neuroendocrine control of reproduction and traces back their origin along the vertebrate lineage and in other metazoa before the emergence of vertebrates. A focus is given on how gene duplications, resulting from either local events or from whole genome duplication events, and followed by paralogous gene loss or conservation, might have shaped the evolutionary scenarios of current families of key actors of the gonadotropic axis.

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Section: Gnrh Receptors In Mammalsmentioning

confidence: 99%

Origin and Evolution of the Neuroendocrine Control of Reproduction in Vertebrates, With Special Focus on Genome and Gene Duplications

Dufour

Quérat

Tostivint

et al. 2020

Physiological Reviews

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“…As demonstrated by several previous studies, cancerous immunoglobulins are essential for growth/proliferation of cancer cells, which was judged from several hypothesized mechanisms of actions as well as siRNA inhibition studies [5][6][7]. GHR106 Mab, on the other hand was found to react specifically with GnRH (Gonadotropin releasing hormone) receptor, which was widely expressed on the surface of almost all cancer cells [8][9][10][11][12][13][14][15][16]. This Mab was found to have biological actions similar to those of decade peptide analogs of GnRH [9,17], including their respective patterns in gene regulations, and induced apoptosis to ovarian and many other cancer cells [9,17].…”

Section: Background Informationmentioning

confidence: 99%

“…GHR106 Mab is of murine origin and was converted to humanized forms designated as hGHR106 through the established procedures as described for hRP215 [20]. GHR106 recognizes specifically the extracellular domains of human GnRH receptor, which is highly expressed on the surface of cancer cells of many human tissue origins [8][9][10][11][12][13][14][15][16]. hGHR106 can be utilized for therapeutic applications in GnRH hormone sensitive ovarian cancers and others as well as in the control of fertility regulations [27][28][29].…”

Section: Humanized Forms Of Monoclonal Antibodies To Human Gnrh Receptor Hghr106mentioning

confidence: 99%

Two Distinct Humanized Monoclonal Antibodies for Immunotherapy of Ovarian Cancer

Lee¹

2014

J Cancer Sci Ther

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Two monoclonal antibodies (Mab) were selected for development of anti-cancer drugs targeting ovarian cancer.RP215 Mab was shown to react with a carbohydrate-associated epitope detected mainly in the heavy chains of cancer cell-expressed immunoglobulins which are essential for the growth/proliferation of almost all human cancer cells. GHR106 Mab, on the other hand, reacts specifically with GnRH receptor on the surface of almost all cancer cells. In this review, efforts were made to use an ovarian cancer cell line, OC-3-VGH as the experimental model to study these two Mabs in murine and humanized isoforms including humanization, comparative biochemical and immunological characterizations. Surface binding of either of these two Mabs can result in apoptosis and complement-dependent cellular cytotoxicity to this ovarian cancer cell line and others. Both murine Mabs were humanized and shown to be bioequivalent with respect to affinity and biospecificity to their murine counterparts through extensive biochemical/immunological studies. Therefore, preclinical and clinical studies were warranted to continue the investigations of these two potential anti-cancer drug candidates for therapeutic treatments of ovarian cancer.

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“…Gonadotropin-releasing hormone (GnRH), a decapeptide hormone released from the hypothalamus, is the central activator of the reproductive hormonal network [ 1 , 2 ]. GnRH receptor (GnRHR) is a G-protein-coupled cell surface receptor (GPCR) with seven-transmembrane-spanning domains connected by extracellular and intracellular loops [ 3 , 4 ]. As one of the GPCR families, GnRHR transduces the intracellular GPCR signals via multiple heterotrimeric G proteins [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-metastatic effect of GV1001 on prostate cancer cells; roles of GnRHR-mediated Gαs-cAMP pathway and AR-YAP1 axis

et al. 2021

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Background Gonadotropin-releasing hormone receptor (GnRHR) transmits its signal via two major Gα-proteins, primarily Gαq and Gαi. However, the precise mechanism underlying the functions of Gαs signal in prostate cancer cells is still unclear. We have previously identified that GV1001, a fragment of the human telomerase reverse transcriptase, functions as a biased GnRHR ligand to selectively stimulate the Gαs/cAMP pathway. Here, we tried to reveal the potential mechanisms of which GV1001-stimulated Gαs-cAMP signaling pathway reduces the migration and metastasis of prostate cancer (PCa) cells. Methods The expression of epithelial-mesenchymal transition (EMT)-related genes was measured by western-blotting and spheroid formation on ultra-low attachment plate was detected after GV1001 treatment. In vivo Spleen-liver metastasis mouse model was used to explore the inhibitory effect of GV1001 on metastatic ability of PCa and the transwell migration assay was performed to identify whether GV1001 had a suppressive effect on cell migration in vitro. In order to demonstrate the interaction between androgen receptor (AR) and YAP1, co-immunoprecipitation (co-IP), immunofluorescence (IF) staining, chromatin immunoprecipitation (ChIP) were performed in LNCaP cells with and without GV1001 treatment. Results GV1001 inhibited expression of EMT-related genes and spheroid formation. GV1001 also suppressed in vivo spleen-liver metastasis of LNCaP cells as well as cell migration in vitro. GV1001 enhanced the phosphorylation of AR and transcription activity of androgen response element reporter gene through cAMP/protein kinase A pathway. Moreover, GV1001 increased Ser-127 phosphorylation of YAP1 and its ubiquitination, and subsequently decreased the levels of AR-YAP1 binding in the promoter region of the CTGF gene. In contrast, both protein and mRNA levels of NKX3.1 known for tumor suppressor gene and AR-coregulator were upregulated by GV1001 in LNCaP cells. YAP1 knockout using CRISPR/Cas9 significantly suppressed the migration ability of LNCaP cells, and GV1001 did not affect the cell migration of YAP1-deficient LNCaP cells. On the contrary, cell migration was more potentiated in LNCaP cells overexpressing YAP5SA, a constitutively active form of YAP1, which was not changed by GV1001 treatment. Conclusions Overall, this study reveals an essential role of AR-YAP1 in the regulation of PCa cell migration, and provides evidence that GV1001 could be a novel GnRHR ligand to inhibit metastasis of PCa via the Gαs/cAMP pathway.

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Molecular cloning and expression of cDNA encoding the murine gonadotropin-releasing hormone receptor.

Cited by 218 publications

References 43 publications

Origin and Evolution of the Neuroendocrine Control of Reproduction in Vertebrates, With Special Focus on Genome and Gene Duplications

Origin and Evolution of the Neuroendocrine Control of Reproduction in Vertebrates, With Special Focus on Genome and Gene Duplications

Two Distinct Humanized Monoclonal Antibodies for Immunotherapy of Ovarian Cancer

Anti-metastatic effect of GV1001 on prostate cancer cells; roles of GnRHR-mediated Gαs-cAMP pathway and AR-YAP1 axis

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