2000 Fiscal Year Final Research Report Summary
Hormonal regulation of production and activation of immunoglobulin binding factor.
| Project/Area Number |
09671686
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KAMADA Masaharu Univ.of Tokushima, School of Medicine, Associate Professor, 医学部, 助教授 (60145018)
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| Co-Investigator(Kenkyū-buntansha) |
FUTAKI Siroh Univ.of Kyoto, Chemical Institute, Associate Professor, 化学研究所, 助教授 (50199402)
KIDO Hiroshi Univ.of Tokushima, Institute for Enzyme, Research Professor, 分子酵素学研究センター, 教授 (50144978)
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| Project Period (FY) |
1997 – 2000
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| Keywords | immunoglobulin binding factor / uterine cervical gland / antisperm antibody / molecular chaperon / estrogen / progesterone / protein disulfide isomerase / hormone replacenment therapy |
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| Research Abstract |
Uterine cervical mucus contains a factor that binds immunoglobulin (IgBF), related to the Fcγ receptor. IgBF is activated to bind immunoglobulin by the enzyme, protein disulfide isomerase (PDI), which distributes widely in the tissues of the human female reproductive tract. It may play a role in preventing antibody production against allegenic sperm in the female reproductive tract. To elucidate the regulatory mechanism involved in the production of activated IgBF, we determined the expression of IgBF mRNA in the human female reproductive tract. Also the effects of hormones on the expression of IgBF and PDI mRNAs in rat uterine cervix and in a human cervical adenocarcinoma cell line were examined. Total RNA was prepared from the endocervix, endometrium, fallopian tubes and ovaries obtained from surgical specimens in the treatment of various benign gynecologic diseases. RT-PCR was performed to amplify the cDNA coding IgBF.PCR products were electrophoresed in agarose get and the respecti
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ve transcripts were determined.In the experimental study, hypophysectomized female rats were superovulated. The uterine cervices were excised at preovulatory, ovulatory and postovulatory phases. The uterine cervical adenocarcinoma cells (TCO-2) were cultured for 24h in serum-free medium containing 17 β-estradiol or progesterone. The tissue content of mRNAs for IgBF and PDI was determined by quantitative RT-PCR using ABI PRISM 7700. Only the endocervical glands transcribe IgBF mRNA.The ratio of IgBF/GAPDH was highest during the ovulatory phase compared to the preovulatory (p<0.02) or postovulatory (p<0.01) phases. Similarly, the expression of PDI mRNA was highest at the ovulatory phase, lower at the preovulatory phase (p<0.02) and at the postovulatory phase (p<0.01). 17β-estradiol stimulated the expression of both mRNAs of IgBF and PDI in human uterine cervical adenocarcinoma cells ; whereas progesterone was ineffective. In conclusion, estrogen may regulate the production of IgBF by the endocervix and the activating enzyme PDI in vivo and is responsible for the increased level of the activated IgBF in the female reproductive tract during the ovulatory phase, allowing allogenic sperm to enter the uterine cavity.
Immunosenescence is associated with the occurrence of lethal diseases, such as infection and malignancy. Since endocrinosenescence occurs simultaneously with immunosenescence, we determined whether or not immune systems were altered in postmenopausal women. Also the ability of hormone replacement therapy (HRT) to reverse or modify the aberrations of the immune functions in elderly women were examined. Decrease of peripheral blood lymphocyte (%) and serum level of M-CSF, and increase of production of proinflammatory cytokines (IL-1 and TNF-α) and of Th2 cytokine (IL-10) occured after menopause and HRT improved these changes to the levels observed in premenopausal women. In conclusion, it is likely that the desirable effects of HRT on the debilitating conditions are mediated at least in part by an improvement of the immune system. Less
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