1993 Fiscal Year Final Research Report Summary
A study on the factors controlling bone metabolism
| Project/Area Number |
04670992
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ASO Takeshi Tokyo Medical and Dental University, Department of Obstetrics and Gynecology Professor, 医学部, 教授 (60093176)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Hitoshi Tokyo Medical and Dental University, Department of Obstetrics and Gynecology, As, 医学部, 助手 (60233889)
KOYAMA Takao Tokyo Medical and Dental University, Department of Obstetrics and Gynecology, As, 医学部, 助教授 (40092407)
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| Project Period (FY) |
1992 – 1993
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| Keywords | bone metabolism / estrogen / vitamin D3 / Kampo medicine / osteoblast / osteoclast / GnRH agonist / anti-cancer agent |
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| Research Abstract |
The bone metabolism is cotrolled by various factors. In this study, three experiments were conducted to add new informations concerning the influences of hyposestrogenism, anti-cancer chemotherapy and progesterone on the metabolism.
In the first experiment, estrogen production of the ovary was suppressed in female mature rats by gonadotropin releasing hormone agonist(GnRH-A) for 10 weeks. The mineral bone density, the findings of contact microradiogram, and osteogenic parameters were analyzed at the end of treatment period. A group of rats was administered HACHIMI-JIO-GAN (HJG), a Kampo medicine simultaneously. The increased bone absorption due to the decreased of the width of trabecular was detected in the GnRH-A treated rats. Such changes were reversed by the HJG administration by which the cell number and cell surface of osteoclast were reduced.
The second experiment concerned the negative effects of cisplatin, an anti-cancer agent for gynecological malignacies on vitamin D3 mtabolism. In the patients who were given this agent exhibited marked decrease of 1,25-dihydrovitamin D3. It was indicative that the toxic action of cisplatin on the distal tubules of kidney induced the dysfuncion of vitamin D3 metabolism, and the bone loss of such patients was accelerated.
The influence of progesterone on the osteoblast function was investigated in an in vitro experiment. The production of TGF-beta from the cultured human osteosarcoma cells was enhanced by progesterone. The increased mRNA expression of TGF-beta in human osteoblast was detected by northern bolt analysis in the conditions stimulated by progesterone. It is suggested that progesterone plays a role in the coupling of osteoblast and osteoclast cell functions.
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