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研究生:井洌
研究生(外文):Lieh Gian
論文名稱:丙烷基硫尿嘧啶對雄性大鼠腎上腺皮質束網狀帶細胞分泌皮質固酮之長期效應
論文名稱(外文):Chronic Effect of Propylthiouracil on Corticosterone Production by Zona Fasciculata-Reticularis Cells in Male Rats
指導教授:王錫崗王錫崗引用關係
指導教授(外文):Paulus S. Wang
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:51
中文關鍵詞:丙烷基硫尿嘧啶腎上腺皮質束網狀帶皮質固酮長期效應
外文關鍵詞:PropylthiouracilZona Fasciculata-Reticularis CellsCorticosteroneChronic Effect
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過去研究指出,甲狀腺激素影響腎上腺皮質細胞分泌皮質固酮。本實驗室曾發現,不論是甲狀腺素或是丙烷基硫尿嘧啶(PTU,一種抗甲狀腺藥物),都會經由降低類固醇合成酶的活性,以及環單磷酸腺苷的合成,降低大鼠腎上腺皮質細胞分泌皮質固酮。本論文旨在研究長期處理丙烷基硫尿嘧啶,對大鼠腎上腺皮質束網狀帶細胞類固醇生合成的作用及其機轉。雄鼠每天皮下注射丙烷基硫尿嘧啶(20 mg/ml/kg)或甲狀腺素(25 μg/ml/kg),連續七日。對照組動物只注射鹼性生理鹽水。最後一次注射二十小時後,所有動物斷頭犧牲,收集血樣。大鼠腎上腺皮質經膠原酵素處理製備束網狀帶細胞,分別與腎上腺皮質促素(ACTH, 10-9M)、forskolin (adenylyl cyclase的活化劑, 10-5M)、8-Br-cAMP(cAMP的類似物, 10-5M),或去羥基皮質固酮(DOC,皮質固酮的前驅物, 10-5M)在充滿95%氧和5%二氧化碳的37℃水浴箱中培養一小時。細胞培養液及血漿皮質固酮濃度是用放射免疫測定法檢測。結果發現經丙烷基硫尿嘧啶處理的大鼠,其束網狀帶細胞,不論是基礎值或以藥物刺激,皮質固酮分泌均較對照者多;但甲狀腺素處理組則無此現象。長期注射甲狀腺素及丙烷基硫尿嘧啶的大鼠,在給予ACTH、forskolin、8-Br-cAMP及DOC刺激皮質固酮分泌時,因丙烷基硫尿嘧啶引發的刺激效應則受到抑制。長期處理丙烷基硫尿嘧啶大鼠血漿皮質固酮及腎上腺皮質促素的濃度均偏低。上述結果顯示,長期處理丙烷基硫尿嘧啶對大鼠腎上腺束網狀帶細胞分泌皮質固酮的刺激效應,至少有部分原因係由於甲狀腺功能偏低所致。
The effect of thyroid hormones on the release of corticosterone by adrenal zona fasciculata-reticularis (ZFR) cells have investigated. We have previously found that administration of either thyroid hormones or propylthiouracil (PTU, an antithyroid drug) decreases the production of corticosterone in rat adrenocortical cells via the reduction of the activities of steroidogenic enzymes and the generation of cyclic AMP. The main objectives of the present study were to investigate the long-term effects of PTU and its action mechanisms on the steroidogenesis in ZFR cells of rats adrenal gland. Male rats were injected subcutaneously with PTU (20 mg/ml/kg) and/or thyroxine (T4, 25μg/ml/kg) once daily for two weeks. PTU and T4 were dissolved in alkaline saline. The control animals were injected with alkaline saline only. Twenty hours after the last injection, all experimental rats were decapitated. The blood samples were collected and the ZFR cells were prepared by the administration of collagenase. Rat ZFR cells were in vitro treated with adrenocorticotropin (ACTH, 10-9M), forskolin (an activator of adenylyl cyclase,10-5M), 8-bromo-cyclic AMP (8-Br-cAMP, a permeable analogue of cAMP, 10-5M), or deoxycorticosterone (DOC, a steroidogenic precursor of corticosterone, 10-5M) under 95% O2 + 5% CO2 at 37℃ for one hour. The concentrations of corticosterone in the medium and plasma samples were measured by radioimmunoassay. The production of corticosterone by rat ZFR cells was stimulated by ACTH, forskolin, 8-Br-cAMP, and DOC in vitro. Both the basal and evoked levels of corticosterone production were enhanced in ZFR cells from PTU-treated rats, but not in that from T4-treated animals. However, chronic administration of T4 attenuated the stimulatory effect of PTU on the production of corticosterone in response to ACTH, forskolin, 8-Br-cAMP and DOC. The concentrations of plasma corticosterone and ACTH were decreased by chronic administration of PTU. These data suggest that the stimulatory effect of chronic administration of PTU on corticosterone production in ZFR cells is in part due to hypothyroidism in male rats.
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