Disease relevance of GNRH2

• Thus, in the present study a role for progesterone (P4) in the regulation of GnRH I, GnRH II, and GnRHRI was investigated using a human neuronal medulloblastoma cell line (TE671) as an in vitro model [1].
• Further, exposure of normal or cancerous human or mouse T cells to GnRH-II or GnRH-I triggered de novo gene transcription and cell-surface expression of a 67-kD non-integrin laminin receptor that is involved in cellular adhesion and migration and in tumor invasion and metastasis [2].
• However, the expression and role of GnRH-II in human OSE and ovarian carcinomas is not known [3].
• Recently, a second type of GnRH receptor, specific for GnRH-II, has been identified in ovarian and endometrial cancers, which transmits significantly stronger antiproliferative effects than the GnRH-I receptor [4].
• In the present study, we studied the possible implication of GnRH II in endometriosis [5].

Psychiatry related information on GNRH2

• In mammals, GnRH-II has been shown to regulate reproductive and feeding behaviors [6].

High impact information on GNRH2

• We find here that human normal and leukemic T cells produce GnRH-II and GnRH-I [2].
• Can T cells be directly activated to de novo gene expression by gonadotropin-releasing hormone-II (GnRH-II), a unique 10-amino-acid neuropeptide conserved through 500 million years of evolution [2]?
• GnRH-II or GnRH-I also induced adhesion to laminin and chemotaxis toward SDF-1alpha, and augmented entry in vivo of metastatic T-lymphoma into the spleen and bone marrow [2].
• Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans [7].
• The human gene homolog of this receptor, however, has a frame-shift and stop codon, and it appears that GnRH II signaling occurs through the type I GnRH receptor [8].

Chemical compound and disease context of GNRH2

• Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on prostate cancer cell signaling and death [9].
• OBJECTIVE: This study demonstrates differential effects of GnRH-I and GnRH-II on androgen-independent human prostate cancer cells [9].

Biological context of GNRH2

• Comparative genomics of the endocrine systems in humans and chimpanzees with special reference to GNRH2 and UCN2 and their receptors [10].
• We show here that a gene encoding GnRH-II is expressed in humans and is located on chromosome 20p13, distinct from the GnRH-I gene that is on 8p21-p11 [11].
• Two putative E-box binding sites and one Ets-like element were identified within the first exon, and mutational analysis demonstrated that these cis-acting elements functioned cooperatively to stimulate the human GnRH-II gene transcription [12].
• This study was conducted to investigate whether or not the receptor specific for GnRH type II is expressed in human endometrial and ovarian cancer cells and whether or not GnRH-II has effects on tumor cell proliferation [13].
• GnRH I and GnRH II mRNA transcripts were detected in first-trimester placenta, whereas only GnRH I was detected in tissues obtained at term [14].

Anatomical context of GNRH2

• In the corpus luteum, significant levels of GnRH-I, GnRH-II, as well as GnRHR were observed in granulosa luteal cells, but not in theca luteal cells [15].
• In addition to hypothalamic GnRH (GnRH-I), a second GnRH form (pGln-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly; GnRH-II) with unknown function has been localized to the midbrain of many vertebrates [11].
• GnRH I and GnRH II were also found to be coexpressed in first-trimester decidua and primary cultures of decidual stromal cells [14].
• Collectively, these observations demonstrate that GnRH I and GnRH II have both common and discrete cellular distributions in the placenta and decidua and suggest that these two hormones are capable of eliciting their biological actions in an autocrine and/or paracrine manner within and between these maternal and fetal cellular compartments [14].
• In contrast, GnRH I but not GnRH II was expressed in the outer multinucleated syncytial trophoblast layer of first trimester chorionic villi and in cultures of villous cytotrophoblasts allowed to undergo differentiation and fusion in vitro [14].

Associations of GNRH2 with chemical compounds

• Immunolocalization of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Type I GnRH Receptor during Follicular Development in the Human Ovary [15].
• This stimulatory effect of P4 in the regulation of GnRH I mRNAs was significantly attenuated by RU486, whereas no significant difference in the expression level of GnRH II was observed with P4 or RU496 [1].
• Although recent studies have shown that the expression of the human GnRH-II gene is regulated by cAMP and estrogen, the molecular mechanisms governing its basal transcription remain poorly understood [12].
• Mutating Asp(2.61(97)) to Glu or Ala, Asn(2.65(101)) to Ala, or Lys(3.32(120)) to Gln decreased potency of GnRH II-stimulated inositol phosphate production [16].
• Both GnRH-II and GnRH-II-a inhibited basal and hCG-stimulated progesterone secretion, effects which were similar to the effects of GnRH-I treatment on ovarian steroidogenesis [17].

Physical interactions of GNRH2

• We have demonstrated that certain Ala mutations in the intracellular segments of transmembrane domains 3 (Met(132)), 5 (Met(227)), 6 (Phe(272) and Phe(276)), and 7 (Ile(322) and Tyr(323)) of the human GnRH receptor allosterically increased ligand binding affinity for GnRH II but had little effect on GnRH I binding affinity [18].
• Chromatin immunoprecipitation assay showed that p-CREB bound the CRE within the endogenous GnRH-II promoter within 1 h and that p-CREB association with C/EBPbeta occurs within 2 h of cAMP stimulation, coincident with the first appearance of C/EBPbeta at the CRE [19].

Regulatory relationships of GNRH2

• The present study attempted to demonstrate whether GnRH-I and GnRH-II induce differential desensitisation of GnRHR and to identify the motif involved [20].
• Western blot analysis demonstrated that ERK1/2 was activated by GnRH-II (100 nm) [21].
• On the other hand, it is not likely that GnRH-II activates the JNK/SAPK pathway [21].
• Taken together, these results indicate that p38 MAPK is involved in the GnRH-II-induced inhibition of cell growth through activator protein-1 activation, which may be related to induction of apoptosis in ovarian cancer cells [22].

Other interactions of GNRH2

• Differential role of progesterone receptor isoforms in the transcriptional regulation of human gonadotropin-releasing hormone I (GnRH I) receptor, GnRH I, and GnRH II [1].
• GnRH I and GnRH II were found to increase MMP-2 and MMP-9 mRNA and protein levels in these primary cell cultures in a dose- and time-dependent manner using quantitative competitive-PCR and ELISA [23].
• The proliferation of these cells is dose- and time-dependently reduced by GnRH-II in a greater extent than by GnRH-I (GnRH, LHRH) superagonists [24].
• A receptor specific for GnRH-II (type II GnRH receptor) has been identified in non-mammalian vertebrates as well as in primates, but not yet in humans [25].
• In contrast, GnRH I increased, whereas GnRH II decreased PAI-1 mRNA and protein expression levels in these cells [26].

Analytical, diagnostic and therapeutic context of GNRH2

• The mRNA levels of GnRH I and GnRH II were analyzed by RT-PCR [1].
• GnRH I and GnRH II increased uPA mRNA and protein expression levels in these primary cell cultures in a dose- and time-dependent manner [26].
• In these studies, we localized GnRH I and GnRH II expression in human placenta and decidua to distinct subpopulations of cells isolated from these tissues and in a chorionic villous/decidual tissue coculture system that mimics many of the cellular events of early placentation [14].
• Expression of GnRH-II receptor mRNA in endometrial and ovarian cancer cell lines was demonstrated using RT-PCR and Southern blot analysis [13].
• The GnRH-I and GnRH-II promoters were isolated by PCR using human genomic DNA and cloned into the luciferase reporter plasmid [27].

References