1992 Fiscal Year Final Research Report Summary
Disorder of steroidogeneis and defective repair of DNA in genetic disorder of lipid metabolism by the rat
| Project/Area Number |
03670112
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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 |
General pharmacology
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
MASUBUCHI Yoshiko St.Marianna Univ.Sch. of Med., Dept. of Pharmacology, Associate Professor, 医学部, 助教授 (10081639)
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| Co-Investigator(Kenkyū-buntansha) |
AKAIKE Mari St.Marianna Univ.Sch. of Med., Dept. of Pharmacology, Assistant, 医学部, 助手 (70211000)
WATANABE Minoru St.Marianna Univ.Sch. of Med., Dept. of Pharmacology, Assistant, 医学部, 助手 (10191800)
TANAKA Masami St.Marianna Univ.Sch. of Med., Dept. of Pharmacology, Assistant Professor, 医学部, 講師 (00171801)
KUMAI Toshio St.Marianna Univ.Sch. of Med., Dept. of Pharmacology, Assistant Professor, 医学部, 講師 (40139671)
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| Project Period (FY) |
1991 – 1992
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| Keywords | Hypercholesterolemia / Chromosome-aberration / Alkylation / Ventral prostate / Androben-receptor / Steroid hormones / SHR / prostatic carcinoma |
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| Research Abstract |
I. We developed spontaneously hypercholesterolemic rats (HLR) from selective brother-sister mating of Sprague Dawley rat (SD). We found a significant decrease of steroidogenesis in both sex suggesting hypogonadism. Contrally, hypercorticalism was found in HLR of both sex, and it may be caused by an enlargement of the cholesterol pool size in adrenal coming from high levels of cholesterol in HLR. The androgen receptor of the ventral prostate in HLR showed a high Kd and a low Bmax in intact rat but increases in Kd and Bmax after the castration.
The results demonstrated that (1) genetically, HLR showed a disturbance of gonadal steroidogenesis, leading to insufficience of fertility and sterility, and that (2) result in adrenal hypocorticalism may represent an enlargement of cholesterol pool size and facilitate 11beta-hydroxylation, 18-hydroxylation and lipoprotein-transportation, and that (3) androgen variants may appear in the receptor of ventral prostate.
II. Abnormal responses of lymphocytes to Bleomycin-induced chromosome aberration in normal aging and genetic hypercholesterolemic rat (HLR).
The present work revealed chromosome aberration was tend to low value (partially, significantly low) in HLR. This led to the existance of dysfunction of repair-mechanism to double-stranded lesion of DNA induced by BLM in HLR.
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