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Follicular atresia : ウィキペディア英語版 | Follicular atresia Follicular atresia is the breakdown of the ovarian follicles, which consist of an oocyte surrounded by granulosa cells and internal and external theca cells. It occurs continually throughout a woman's life, as she is born with millions of follicles but will only ovulate around 400 times in her lifetime.〔(M. J. "Follicle dynamics during ovarian ageing." Molecular and cellular endocrinology 163.1 (2000): 43-48. )〕〔(Elizabeth, and Elizabeth A. Young. "Methodological issues in the study of hormone-behavior relations in humans: Understanding and monitoring the menstrual cycle." Sex differences in the brain. From genes to behavior (2008): 63-78. )〕 ==Mechanism== Follicular atresia is inhibited by follicle-stimulating hormone (FSH), which promotes follicle development.〔(Antti, and Aaron JW Hsueh. "Regulation of ovarian follicle atresia." Annual review of physiology 59.1 (1997): 349-363. )〕 Once the follicle has developed, it secretes estrogen, which in high levels decreases secretions of FSH.〔(J. C., et al. "Selective inhibition of follicle-stimulating hormone secretion by estradiol. Mechanism for modulation of gonadotropin responses to low dose pulses of gonadotropin-releasing hormone." Journal of Clinical Investigation 71.2 (1983): 248. )〕 Granulosa cell apoptosis is considered the underlying mechanism of follicular atresia, and has been associated with five ligand-receptor systems involved in cell death:〔(Noboru, et al. "Regulation mechanism of selective atresia in porcine follicles: regulation of granulosa cell apoptosis during atresia." The Journal of reproduction and development 50.5 (2004): 493. )〕 *Tumor necrosis factor alpha (TNFα) and receptors *Fas ligand and receptors *TNF-related apoptosis-inducing ligand (TRAIL or APO-2) and receptors *APO-3 ligand and receptors *PFG-5 ligand and receptors Granulosa cell apoptosis is promoted by tumor necrosis factor-alpha (TNFα), though the mechanism of TNFα is unclear.〔(Ravid, et al. "Induction of apoptosis in granulosa cells by TNFα and its attenuation by glucocorticoids involve modulation of Bcl-2." Biochemical and biophysical research communications 294.1 (2002): 51-59. )〕〔(Hakan, I. T. S. U. K. O. Furuta, and A. J. Hsueh. "Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis." Endocrinology 133.5 (1993): 2204-2212. )〕 Fas antigen, a cell surface receptor protein that is expressed on granulosa cells, mediates signals that induce apoptosis by binding Fas ligand and therefore plays an important role in follicular atresia. Lack of a functional Fas ligand / Fas receptor system has been linked to abnormal follicle development, and greater numbers of secondary follicles as a result of the inability to induce apoptosis.〔(Kazuhiro, et al. "Involvement of Fas antigen in ovarian follicular atresia and luteolysis." Molecular reproduction and development 47.1 (1997): 11-18. )〕 TNF-related apoptosis-inducing ligand TRAIL activates Caspase 3 (CASP3), which in turn interacts with caspases 6, 7, 8, 9, and 10 to induce apoptosis in granulosa cells.〔(Naoko, et al. "Roles of tumor necrosis factor-related apoptosis-inducing ligand signaling pathway in granulosa cell apoptosis during atresia in pig ovaries." Journal of Reproduction and Development 49.4 (2003): 313-321. )〕
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