Disease relevance of RXFP2

• Agents acting at RXFP2 receptors may be useful for the treatment of cryptorchidism and infertility, whereas antagonists may be used as contraceptives [1].
• Activators of RXFP2 may be useful to treat cryptorchidism and infertility and inhibitors have potential as contraceptives [2].
• These findings suggest that LGR8 signaling may be involved in sensorimotor control in the rat and perhaps other species, particularly via actions on parafascicular neurons that project to basal ganglia and are depleted in Parkinson's disease [3].
• Nitrates, nitrites and gastric cancer in Great Britain [4].
• Tamoxifen citrate (Nolvadex [Great Britain]; no comparable US product) is a recently developed antiestrogen with significant activity against metastatic breast cancer in postmenopausal women [5].

Psychiatry related information on RXFP2

• Chemical defense mechanisms on the Great Barrier Reef, Australia [6].
• Some human cases of the transmissible neurodegenerative disorder Creutzfeldt-Jakob disease recently seen in Great Britain are thought to have resulted from eating beef infected with the agent of bovine spongiform encephalopathy [7].
• BACKGROUND: The Great Smoky Mountains Study of youth focuses on the relationship between the development of psychiatric disorder and the need for and use of mental health services [8].
• The Great Smoky Mountains Study of Youth. Functional impairment and serious emotional disturbance [9].
• The authors aimed to establish obsessive-compulsive disorder prevalence and its clinical typology among adults in private households in Great Britain and to obtain generalizable estimates of impairment and help-seeking [10].

High impact information on RXFP2

• They reached the northern Alps and Paris on 30 April, southern Great Britain on 2 May, the southern North Sea on 3 May, and the northern North Sea on 3 May and again on 8 May [11].
• RXFP1 and RXFP2 are leucine-rich repeat-containing G-protein-coupled receptors with complex binding characteristics involving both the large ectodomain and the transmembrane loops [1].
• It has been proposed that nitrilotriacetic acid be substituted for trisodium polyphosphates in detergents as a way to reduce the rate of eutrophication in the Great Lake Basin. The reaction of nitrilotriacetic acid with chlorine-containing solutions produces a hitherto unknown degradation production, N-formyliminodiacetic acid, in high yield [12].
• The recent awareness and interest in the pharmacology and toxicology of uncultivated mushrooms in North America and Great Britain should encourage continued active research [13].
• Reports from the Netherlands, Great Britain, Australia, and New Zealand indicate that avoiding the prone position for infants in the first 6 months of life could reduce the number of SIDS deaths by as much as 50% [14].

Chemical compound and disease context of RXFP2

• BACKGROUND & AIMS: Acetaminophen toxicity is the most common cause of acute liver failure (ALF) in the United States and Great Britain, but may be underrecognized in certain settings [15].
• One major observation of this literature search is that permethrin is the treatment of choice for lice and scabies in the US and in Great Britain, whereas lindane is still recommended for scabies in most other European countries because of its longer-standing record of effectiveness [16].
• Seasonal incidence of Vibrio vulnificus in the Great Bay estuary of New Hampshire and Maine [17].
• CONCLUSION: Great caution should be exercised in the post hoc interpretation of the potential efficacy of nonrandomized treatments such as heparin therapy derived from phase III clinical data of other drugs for sepsis [18].
• Angiosarcoma of the liver: a marker tumour for the late effects of Thorotrast in Great Britain [19].

Biological context of RXFP2

• Eight reporter genes were tested at both receptors as a screen to identify other signaling pathways activated by RXFP1 and RXFP2 [20].
• Comparisons between RXFP1, RXFP2, the chimeric receptors, and the truncated receptors revealed that the interaction between receptor sites is critical for optimal ligand binding and signal transduction and that the ectodomain is essential for signaling [21].
• RXFP1 and RXFP2 have at least two binding sites - a high-affinity site in the leucine-rich repeat region of the ectodomain and a lower-affinity site in an exoloop of the transmembrane region [2].
• INSL3, in turn, binds LGR8 expressed in germ cells to initiate the meiotic progression of arrested oocytes in preovulatory follicles in vitro and in vivo and to suppress male germ cell apoptosis in vivo [22].
• Treatment of the human anaplastic thyroid carcinoma cell line 8505C with diethylstilbestrol (DES) caused a significant dose-dependent transcriptional down-regulation of INSL-3 and a marked up-regulation of LGR8 [23].

Anatomical context of RXFP2

• Based on the known production of INLS3 by testicular Leydig cells and ovarian theca cells, we demonstrated the expression of the INSL3 receptor LGR8 in oocytes in ovary and in male germ cells in the testis [22].
• Three human prostate carcinoma cell lines displayed differential gene activity for INSL3 and LGR8 [24].
• Prostate epithelial cells were also a source for transcripts encoding the INSL3 receptor LGR8 suggesting the presence of an autocrine/paracrine INSL3-LGR8 ligand-receptor system within the human prostate [24].
• A candidate gene Great (G-protein-coupled receptor affecting testis descent), was identified within the transgene integration site [25].
• The only clinical consequence of alterations of the INSL3-LGR8/GREAT system seems to be failure of the testis to normally descend in the scrotum during embryonic development, without affecting the spermatogenic and endocrine components of the testis itself [26].

Associations of RXFP2 with chemical compounds

• Activation of RXFP1 or RXFP2 causes increased cAMP and the initial response for both receptors is the resultant of Gs-mediated activation and G(oB)-mediated inhibition of adenylate cyclase [2].
• All-trans-retinoic acid was demonstrated in PC-3 to up-regulate LGR8 gene activity in a dose- and time-dependent manner while having no effect on INSL3 gene activity [24].
• In the anaplastic thyroid carcinoma cell line 8505C, the regulation of both INSL-3 and LGR8 by estrogen may be the first indication of a novel hormonally responsive, auto-/paracrine INSL-3 LGR8 ligand receptor system active in human thyroid carcinoma cells [23].
• Alanine-substituted analogs were used to identify the key residues of INSL3 that are responsible for the interaction with the ectodomain of LGR8 [27].
• Our latest studies of RLF and LGR8 have revealed that the N-terminal region of the A chain is not required for receptor binding but is indispensable for cyclic AMP generation [28].
• Our results show that negative cooperativity is present and that INSL3-RXFP2 binding shows both similarities and differences with insulin binding to the insulin receptor [29].

Physical interactions of RXFP2

• Here we have investigated the expression of INSL-3 in human thyroid carcinoma cell lines and in the human thyroid gland which has been shown to express transcripts for the G protein coupled INSL-3 receptor LGR8 [23].
• Solution Structure and Characterization of the LGR8 Receptor Binding Surface of Insulin-like Peptide 3 [27].

Regulatory relationships of RXFP2

• To this end, we examined the effect of stimulation of RXFP1 and RXFP2 receptors [expressed in human embryonic kidney (HEK) 293T cells] with human relaxin family peptides on a number of transcription factor-response elements coupled to reporter genes [20].
• In addition to expressing INSL3 mRNA, the LGR8-negative DU-145 also expressed an INSL3 splice form formerly demonstrated in thyroid carcinoma cells [24].
• A postal survey of pharmacists in a random sample of community pharmacies in Great Britain was carried out to ascertain the factors which influenced their decisions when recommending a product for Over The Counter (OTC) sale [30].

Other interactions of RXFP2

• Comparison of Signaling Pathways Activated by the Relaxin Family Peptide Receptors, RXFP1 and RXFP2, Using Reporter Genes [20].
• RXFP1 and RXFP2 receptors produce increases in intracellular cAMP levels upon stimulation, although the response is complex and contains a component sensitive to PI-3-kinase inhibitors [31].
• In addition, INSL5 (up to 1 microm) shows no affinity or activity at LGR7 or LGR8 either in a binding assay or a bio-functional assay [32].
• Recent studies have demonstrated that relaxin-3 will bind to and activate human LGR7, but not LGR8, in vitro [33].
• The reporter gene studies suggest that ligand stimulation of LGR7 and LGR8 involves cAMP-PKA and p38/JNK signaling [34].

Analytical, diagnostic and therapeutic context of RXFP2

• Northern blot analysis indicated that the LGR8 transcripts are expressed in gubernaculum whereas treatment of cultured gubernacular cells with INSL3 stimulated cAMP production and thymidine incorporation [35].
• Using a combination of mRNA analysis by RT-PCR, immunohistochemistry, ligand-binding, and/or bioactivity assays, the distribution of LGR8 expression was assessed in testicular tissues and cells and in the epididymis [36].
• Quantitative, real-time PCR analysis of the developmental profile of Lgr8 mRNA expression in kidney revealed highest relative levels at late stage gestation (embryonic day 18), with a sharp decrease after birth and lowest levels in the adult [37].
• Thus, using in situ hybridization histochemistry, cells expressing Lgr8 mRNA were observed in glomeruli of renal cortex from adult rats and were tentatively identified as mesangial cells [37].
• Both peptides exhibited similar, but high, receptor binding affinities on human foetal kidney fibroblast 293T cells transfected human LGR8 based on a competition radioreceptor assay with 33P-labelled relaxin H2 (B33) [38].

References