| Project/Area Number |
61303018
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
NAMBARA Toshio Tohoku Univ., Professor, 薬学部, 教授 (30004534)
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| Co-Investigator(Kenkyū-buntansha) |
HONJO Hideo Kyoto Pref. Univ. Med., Assoc. Professor, 産婦人科, 助教授 (30110852)
MIYABO Susumu Fukui Med. School, Professor, 医学部, 教授 (70019884)
NUMAZAWA Mitsuteru Tohoku College Pharm., Professor, 薬学部, 教授 (90006338)
YOSHIZAWA Itsuo Hokkaido Inst. Pharm. Sci., Professor, 薬学部, 教授 (80088864)
TOHMA Masahiko Higashi-Nippon-Gakuen Univ., Professor, 薬学部, 教授 (30001043)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1987: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1986: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | Catechol estrogen / High-performance liquid chromatography / Radioimmunoassay / Comjugated estrogen / Equilenin / Breast cancer / ゴナドトロピン / 抱合型エストロゲン / 電気化学検出高速液体クロマトグラフィー / 芳香核水酸化酵素 / エストロゲンレセプター / エストロゲン依存性腫瘍 |
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| Research Abstract |
In recent years, considerable attention has been focused on the physiological significance of catechol estrogen (CE) in man. We have attempted to establish reliable methods for the determination of CE to clarify its metabolism and disposition in living animals.
Initially, monoglucuronides and monosulfates of 4-hydroxyestrogens and ring Bunsaturated CE were synthesized by unequivocal routes. Development of excellent methods for the analysis of CE was undertaken by two means, namely high-performance liquid chromatography with electrochemical detection (HPLC/ECD) and radioimmunoassay (RIA) with specific antisera. As for HPLC/ECD, pre-column dervatization reagents having the ferrocene moiety as an electrophore proved to be of great use for characterization of CE glucuronides in biological fluids. Also, RIA using specific antisera elicited against hapten [C-6]-BSA conjugates in rabbits was found to be applicable to CE in human blood.
It is sufficiently substantiated that hydroxylations at C-2 and C-16 are principal bioconversions of estrogens. The ring B-unsaturated estrogens underwent similar biotransformations, and the resulting 2- and 16 -hydroxylated metabolites were excreted in rat bile. When estradiol 17-sulfate was incubated with human phenochromocytoma tissue, hydroxylation occurred exclusively at C-2 with retention of the sulfate linkage.
The relationship between breast cancer and estrogen level was investigated. The amount of estrone sulfate in breast cancer tissue was less than the control while the levels of unconjugated estrogens were somewhat higher. The inhibitory effect of CE on the excretion of gonadotrophin was also examined. It was clarified that 2-hydroxyestradiol exhibited no significant influence whereas the potency of 4-hydroxyestradiol was approximately 60% of that of estradiol.
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