| Project/Area Number |
05670890
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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 |
内分泌・代謝学
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| Research Institution | University of Occupational & Environmental Health |
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Principal Investigator |
MORIMOTO Isao Univ.of Occupational & Environmental Health, 1st.Dept.of Int.Med., Associated Professor, 医学部, 助教授 (80145234)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKADA Jyunichi Univ.of Occupational & Environmental Health, 1st.Dept.of Int.Med., Assistant Pro, 医学部, 助手 (20227367)
ETO Sumiya Univ.of Occupational & Environmental Health, 1st.Dept.of Int.Med., Professor, 医学部, 教授 (90010347)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | interleukin-4 / interleukin-6 / parathyroid hormone-related peptide / osteoclast / bone resorption / bone formation / androgen / estrogen / インターロイキン-4 / 破骨細胞 / 骨芽細胞 / サイトカイン / アンドロゲン / エストロゲン |
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| Research Abstract |
1.The receptor, metabolism and effects of androgen in osteoblastic MC3T3-El cells
Androgen receptor (AR) in mouse osteoblasts, MC3T3-El was proved as a transcript of a 10-kb mRNA and as a 110kDa protein. An immunocytochemical study showed that AR was located mainly in the nuclei. Specific binding of ^3H-DHT was observed in both the nuclear and cytosol fractions. The osteoblasts possessed 1190 binding sites per cell and most of the sites situated in the nucleus. Apparent Kd value in the nuclear fraction was 1.35nM for ^3H-DHT binding, and it was similar to that for ^3H-testosterone. 5alpha-reductase activity in the cells was lower than that in classical androgen target tissues. Testosterone and DHT had a similar potency on the cell proliferation. We conclude that testosterone itself acts mainly on the osteoblasts without conversion to DHT.
2.Interleukin-4inhibits spontaneous and parathyroid hormone-related protein (PTHrP) - stimulated osteoclast formation in mice
EC-GI cells which produce
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PTHrP and IL-1 were explanted in nude mice. The tumor-bearing nude mice developed hypercalcemia, and the Ca levels were decreased to near normal level at day 3 by continuous infusion of rmIL-4. When infused with PTHrP (1-34) in ICR mice, rmIL-4 caused a marked inhibitory effect on hypercalcemia induced by PTHrP.Histomorphometric analysis revealed that rmIL-4 inhibits both spontaneous and PTHrP-stimulated osteoclast formation in mice, with a decrease in osteoclastic surface and in the number of osteoclasts per mm bone surface, respectively. We conclude that IL-4inhibits spontaneous and stimulated bone resorption, resulting from inhibition of osteoclast formation.
Effects of IL-4 on bone resorption and bone formation in ovarectomized (OVX) mice
Fourteen days after OVX,serum calcium and alkali-phosphatase were significantly increased. In the analysis of bone histomorphometry 14 and 28 days after OVX,OVX induced high bone turnover, resulting from increase in osteoclastic surface, number of osteoclast per mm bone surface, mineralized surface per mm bone surface and bone mineral apposition rate. These changes induced by OVX were restored with simultaneous administration of IL-4. Serum and urinary IL-6 levels were increased 14 days after OVX,however, the levels were not changed by IL-4 administration. In conclusion, IL-4 antagonizes OVX induced-high bone turnover without modification of IL-6 production. Less
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