| Co-Investigator(Kenkyū-buntansha) |
NAKAGO Satoshi Unversity Hospital, Kobe University Assistant Professor, 医学部・附属病院, 助手 (50283891)
TAKEKIDA Shigeki School of Medicine, Kobe University Assistant Professor, 医学部・附属病院, 助手 (60324927)
SATO Asomi Unversity Hospital, Kobe University Assistant Professor, 医学部・附属病院, 助手 (90314484)
MATSUO Hiroya Unversity Hospital, Kobe University Associate Professor, 医学部・附属病院, 助教授 (60229432)
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| Research Abstract |
1) Sex steroidal regulation of leiomyoma growth and apoptosis.
Progesterone up-regulates the PCNA protein expression in cultured leiomyoma cells. Consistently, the PCNA labeling index in leiomyoma tissues predominated in the secretory, progesterone-dominated, phase of the menstrual cycle, compared to that in the proliferative phase. Furthermore, we demonstrated that EGF-like protein expression in cultured leiomyoma cells was up-regulated by progesterone, whereas EGF receptor expression in those cells was up-regulated by 17β-estradiol. We have also demostrated a greater abundance of Bcl-2 protein in leiomyomas, relative to the normal myometrium of the same individual uterus, and that Bcl-2 protein expression in leiomyoma cells predominated in the secretory, progesterone-dominated phase of the menstrual cycle, compared to that in the proliferative phase. The abundant expression of Bcl-2 protein in leiomyoma may be one of the molecular bases for the enhanced growth of leiomyoma, relative t
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o that of normal myometrium, in the uterus.
2) Granulosa cell proliferation and apoptosis during follicular growth and regression
We examined the proliferative activity of granulosa cells during follicular growth and regression on the basis of PCNA expression. The PCNA expression was augmented by FSH in a dose-dependent manner. FSH, IGF-I and EGF acted as up-regulators of the proliferative activty of granulosa cells, whereas TNFα and TGFβ acted as down-regulators of granulosa cell proliferation. Analysis of DNA 3'-end labeling and Fas antigen and its ligand expression in the ovary suggested that apoptosis in atretic primordial and preantral follicles first occurred in the oocyte, whereas apoptosis in atretic antral follicles first occurred in the granulosa cells. Futhermore, we noted that FSH and IGF-I inhibited apoptosis of granulosa cells, whereas TGFβ and TNFα stimulated apoptosis of the cells. These results suggest that dominant exposure to follicle survival factors such as FSH, IGF-I and EGF may be responsible for the selection of growing follicles, while dominant exposure to atretogenic factors such as TGFβ and TNFα may be responsible for follicle atresia. Less
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