| Project/Area Number |
60571051
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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 |
Biological pharmacy
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| Research Institution | Shizuoka College of Pharmacy |
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Principal Investigator |
TOMITA Takako Shizuoka College of Pharmacy, 薬学部, 助教授 (30046263)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Shizuo Shizuoka College of Pharmacy, 薬学部, 助手 (80106434)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1986: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1985: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Cholesterol esterase / Adipose tissue / Ovariectomy / 17 <beta> -Estradiol / Cyclic AMP-dependent protein kinase / Cyclic AMP / rats / C-AMP |
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| Research Abstract |
The lower risk of coronary heart disease in premenopausal females in comparison with findings in males of an equivalent age has been repeatedly confirmed by clinical observation and epidemiologic studies in coronary heart disease. The beneficial effect of estrogen and the hormonal contribution have drawn great attention. Since high activity of cholesterol esterase(CEase) was found in the adipose tissues, CEase has been assumed to have an important role in the metabolism of plasma cholesterol. CEase is one of enzymes to be phosphorylated to an active form by cyclic AMP-dependent protein kinase(A-kinase). This study was undertaken to investigate regulatory roles of estrogen on CEase activity of either the epididymal or the parametrial adipose tissues in rats.
CEase activity in the supernatant(4300 x g, 15min) of adipose tissue homogenate was assayed using a micellar substrate containing cholesterol <^(14)C> -oleate, taurocholate and phospholipids. CEase activity in the adipose tissue has single peak at pH 7 which shifted to pH 6 by adding 0.025% bovine serum albumine to the buffer. An addition of A-kinase to the assay system enhanced CEase activity greately, but cyclic AMP and ATP did not, suggesting that A-kinase had an regulatory role in this system. Two-month ovariectomy reduced the CEase activity by 41% while the adiministration of water soluble conjugated estrogen(25ug/rat/day) to ovariectomized rats for the same period raised the activity by 65% compared with that of ovariectomized control. Concomitantly, there were a 38%-decrease in A-kinase activity in the enzyme preparation due to ovariectomy and a 50%-increase in the activity due to estrogen treatment. Orchiectomy did not cause any change in CEase activity. These results suggest that 1) CEase activity in adipose tissue is enhanced by endogenous and exogenous estrogens, and that 2) this effect of estrogen on CEase activity is at least partly mediated by the change of A-kinase activity.
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