NCBI Summary:
This gene encodes a protein which contains a C-terminal domain able to interact with the angiotension II (AT2) receptor and a large coiled-coil region allowing dimerization. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the transcript variants has been shown to encode a mitochondrial protein that acts as a tumor suppressor and partcipates in AT2 signaling pathways. Other variants may encode nuclear or transmembrane proteins but it has not been determined whether they also participate in AT2 signaling pathways. [provided by RefSeq, Jul 2008]
General function
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Cellular localization
Mitochondrial
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Ovarian function
Early embryo development
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Influence of tumor necrosis factor-alpha on estradiol, progesterone, insulin-like growth factor-II, and insulin-like growth factor binding protein-1, 2, and 3 in cultured human luteinized granulosa cells. Chae H et al. OBJECTIVE: The objective was to investigate the influence of tumor necrosis factor (TNF)-alpha on estradiol, progesterone, insulin-like growth factor (IGF)-II, and insulin-like growth factor binding protein (IGFBP)-1, 2, and 3 in cultured human luteinized granulosa cells. STUDY DESIGN: Human luteinized granulosa cells were obtained from follicular fluid by transvaginal oocyte aspiration from infertile patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). The cells were cultured for 72h with TNF-alpha at concentrations of 1.0, 10.0, and 100.0ng/ml. The cells not treated with TNF-alpha served as controls. Radioimmunoassay (RIA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to examine the influence of TNF-alpha on estradiol, progesterone, IGF-II, and IGFBP-1, 2, and 3. Results were analyzed using the Kolmogorov-Smirnov test and analysis of variance (ANOVA). Statistical significance was defined as p<0.05. RESULTS: The concentrations of progesterone seemed to decrease as the concentrations of TNF-alpha increased and the concentration of progesterone in the 100.0ng/ml TNF-alpha group was significantly lower than that in the control and other TNF-alpha groups. The expressions of IGF-II mRNA in the 10.0 and 100.0ng/ml TNF-alpha groups were significantly lower than that in the control group. The expressions of IGFBP-2 mRNA seemed to be decreased in the 10.0 and 100.0ng/ml TNF-alpha groups compared with that in the control group, but there were no statistical significances. CONCLUSION: TNF-alpha may play a role as a regulator of human ovarian physiology by modulating the IGF systems in luteinized granulosa cells.
Expression regulated by
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Ovarian localization
Cumulus
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Identification of a novel gene set in human cumulus cells predictive of an oocyte's pregnancy potential. Iager AE et al. OBJECTIVE: To identify a gene expression signature in human cumulus cells (CCs) predictive of pregnancy outcome across multiple clinics, taking into account the clinic and patient variations inherent in IVF practice. DESIGN: Retrospective analysis of single human cumulus-oocyte complexes with the use of a combined microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) approach. SETTING: Multiple private IVF clinics. PATIENT(S): Fifty-eight patients. Samples from 55 of underwent qRT-PCR analysis, and samples from 27 patients resulted in live birth. INTERVENTION(S): Gene expression analysis for correlation with pregnancy outcome on individual human CCs collected immediately after oocyte retrieval. Pregnancy prediction analysis used leave-one-out cross-validation with weighted voting. MAIN OUTCOME MEASURE(S): Combinatorial expression of 12 genes in 101 samples from 58 patients. RESULT(S): We found a set of 12 genes predictive of pregnancy outcome based on their expression levels in CCs. This pregnancy prediction model had an accuracy of 78%, a sensitivity of 72%, a specificity of 84%, a positive predictive value of 81%, and a negative predictive value of 76%. Receiver operating characteristic analysis found an area under the curve of 0.763 ? 0.079, significantly greater than 0.5 (random chance prediction). CONCLUSION(S): Gene expression analysis in human CCs should be considered in identifying oocytes with a high potential to lead to pregnancy in IVF-ET.