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HPMR

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Neurotrophic Tyrosine Kinase, Receptor, Type 3 OKDB#: 2419
 Symbols: NTRK3 Species: human
 Synonyms: TYROSINE KINASE RECEPTOR C, TRKC|NEUROTROPHIN 3 RECEPTOR  Locus: 15q25 in Homo sapiens
HPMR


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General Comment
General function Receptor
Comment
Cellular localization Plasma membrane
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization Oocyte, Granulosa, Theca
Comment Shibayama E, & Koizumi H.( Am J Pathol. 1996) reported that In the reproductive system, TrkA IR was detected in the prostatic epithelial cells, TrkC in the ovarian theca and granulosa cells, TrkA and TrkC in the secretory-phase endometrium, and TrkA in the mammary ducts. Immunocytochemical evidence for the presence and location of the neurotrophin-Trk receptor family in adult human preovulatory ovarian follicles. Seifer DB et al. OBJECTIVE: This study was undertaken to evaluate the presence or absence of neurotrophins and their respective receptors within adult human preovulatory follicles. STUDY DESIGN: Prospective study of neurotrophins and their receptors in follicular cells and unfertilized oocytes from women undergoing aspiration for in vitro fertilization/intracytoplasmic sperm injection. Cells (mural and cumulus granulosa cells, unfertilized oocytes) were examined for immunocytochemical staining of neurotrophin and receptor proteins. RESULTS: Mural and cumulus granulosa cells were positive for BDNF, NT-4/5, NT-3, and NGF, as well as for Trk B, Trk C, and Trk A receptors. Unfertilized oocytes were positive for Trk B, Trk C, and Trk A receptors. CONCLUSION: Neurotrophins and their respective receptor proteins are present within the mural and cumulus granulosa cells of adult human preovulatory follicles. Neurotrophin receptors are present in human unfertilized oocytes. The location of the neurotrophins and their receptors suggest both an autocrine and paracrine function within the adult human ovarian follicle.
Follicle stages Secondary
Comment Expression of neurotrophin 3 and its tropomyosin-related kinase receptor C in?human?preantral follicles. Oron G et al. OBJECTIVE: To investigate the expression of neurotrophin 3 (NT3) and its receptor tropomyosin-related kinase C?(TrkC) in human preantral follicles. Neurotrophins appear to play important roles in preantral follicles. Data on ovarian NT3 and its receptor TrkC are sparse in humans. DESIGN: Immunohistochemical, in situ hybridization, and reverse transcriptase polymerase chain reaction study of the expression of the NT3 system in human ovaries. SETTING: Major tertiary-care academic center. PATIENT(S): Fifteen patients who underwent pregnancy terminations and 36 girls and women who underwent laparoscopies for ovarian surgery. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Laboratory analysis of human ovaries. RESULT(S): NT3 protein staining was identified in oocytes and granulosa cells (GCs) of all samples tested. TrkC protein staining was present in oocytes and GCs of the majority of the fetal samples and in oocytes and GCs of all samples from girls and women. The messenger RNA transcripts for the full-length TrkC isoform were identified in oocytes of the majority of the fetal samples, in all the samples from the girls and women, and in GCs from the girls and women. The two NT3 isoforms and the three TrkC isoforms were identified by reverse transcription polymerase chain reaction in all ovarian extracts. CONCLUSION(S): The presence of NT3 and its TrkC receptor in human preantral follicles, and specifically in GCs, suggests that NT3 may be involved in early folliculogenesis, particularly in the activation of primordial follicles. Dissen GA, et al. (Endocrinology. 1995) found that The NGF and trkA genes showed a different pattern of expression, as the ovarian content of both NGF and trkA mRNA decreased at the time of folliculogenesis. In contrast to the drop in NGF and trkA mRNA expression, NT-4 mRNA levels increased at the time of follicular assembly, coinciding with the abrupt appearance of trkB mRNA. In situ hybridization showed that the increase in NT-4 mRNA expression occurred in a subpopulation of oocytes between 24-48 h after birth, and that the trkB gene became predominantly expressed at this time in epithelial pregranulosa cells. Substantial, but unchanging, levels of NT-3 mRNA and the mRNA encoding trkC, the preferred NT-3 receptor, were detected throughout the perinatal period examined.Ojeda SR,et al.(Mol Cell Endocrinol. 2000) reviewed the neurotrophic and cell-cell dependent control of early follicular development.At least four of the five known neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), and their receptors (p75 NTR, trkA, trkB and trkC) are present in the developing ovary.
Phenotypes
Mutations 1 mutations

Species: None
Mutation name: None
type: null mutation
fertility: None
Comment: Spears N, et al. (Development. 2003) reported that the ovaries of TrkB-/- and TrkC-/- mice with a mixed (129Sv x C57BL/6) genetic background were examined shortly after birth. Around 50% of TrkB-/- mice had grossly abnormal ovaries that contained greatly reduced numbers of follicles. No defects were found in the ovaries of TrkC-/- mice. Congenic TrkB-/- mice were generated on 129Sv and C57BL/6 backgrounds: whereas the former had a mixed ovarian phenotype similar to that of the original colony of mice, the ovaries of all offspring of the C57BL/6 congenic line contained reduced numbers of follicles. RT-PCR showed that mRNA encoding TrkB and its two ligands, neurotrophin 4 (NT4) and brain-derived neurotrophic factor (BDNF), were present throughout the period of follicle formation in the mouse. In situ hybridisation showed that TrkB was expressed primarily in the germ cells before and after follicle formation. Mouse neonatal and fetal ovaries and human fetal ovaries were cultured in the presence of K252a, a potent inhibitor of all Trk receptors. In mice, K252a inhibited the survival of germ cells in newly formed (primordial) follicles. This effect was rescued by the addition of basic fibroblast growth factor (bFGF) to the culture medium. Combined addition of both BDNF and NT4 blocking antibodies lowered germ-cell survival, indicating that these TrkB ligands are required in this process. The results indicate that signalling through TrkB is an important component of the mechanism that regulates the early survival of female germ cells.

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Links
OMIM (Online Mendelian Inheritance in Man: an excellent source of general gene description and genetic information.)
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created: March 16, 2004, 5:36 p.m. by: xin   email:
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last update: March 22, 2011, 3:27 p.m. by: hsueh    email:



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