請用此 Handle URI 來引用此文件: http://hdl.handle.net/11455/12637
標題: Ketoconazole對雄畜睪丸類固醇生合成作用之研究
The Study of Ketoconazole on Testicular Steroidogenesis in Male Animal
作者: 張力天
Chang, Cicero Lee-Tian
關鍵字: ketoconazole
ketoconazole
male animal
MA-10 cells
testis
雄畜
MA-10細胞
睪丸
出版社: 獸醫學系
摘要: 摘 要 Ketoconazole (KCZ)為imidazole類的抗黴菌劑,為瞭解KCZ抑制類固醇內泌素生合成的作用,本實驗利用成年公犬及小鼠睪丸間質細胞瘤MA-10細胞研究KCZ減少雄性素生合成的可能機制。以每日每公斤30 mg KCZ單一口服劑量連續投予公犬七日及以每公斤30 mg KCZ單一口服劑量投予公犬,並分別檢測公犬於服用KCZ前後血清類固醇內泌素生成的變化及服藥後24小時內的血清睪固酮分泌狀況;另外以每公斤30 mg及10 mg KCZ單一口服劑量分別間隔投予對人類絨毛膜性腺激素刺激正常反應之公犬,以檢測公犬於不同劑量KCZ投予前後,以及在人類絨毛膜性腺激素刺激後的血清睪固酮濃度,結果顯示KCZ抑制公犬的助孕素轉換成睪固酮及氫基皮質酮,且呈現對公犬睪固酮分泌之暫時性抑制作用,而對公犬睪固酮分泌之作用具有顯著的劑量差異性 (P<0.05),而此顯著差異性未顯現於KCZ於公犬對人類絨毛膜性腺激素刺激反應下血清睪固酮生合成作用。此外亦利用小鼠睪丸間質細胞瘤MA-10細胞,研究KCZ在in vitro下對睪丸分泌助孕素及環單磷酸核腺之影響,結果指出KCZ抑制間質細胞之adenylate cyclase holoenzyme催化部分之作用。由以上的結果顯示KCZ除了經由選擇性抑制cytochrome P-450相關性酵素及競爭性佔據雄性素受納器外,亦可能藉阻斷adenylate cyclase的活性,來達到抑制睪丸分泌睪固酮的作用。
Summary Ketoconazole (KCZ) is an imidazole antifungal agent. According to the inhibitory effect of KCZ on steroid hormones biosynthesis, our laboratory utilized the adult male dogs and MA-10 mouse Leydig tumor cells for investigating the possible mechanism of causing androgen deficiency by KCZ. The male dogs were orally administrated with 30 mg KCZ/ kg of body weight/day for a week for detecting the changes of serum steroid hormones production. A single oral dose of 30 mg KCZ/ kg of body weight was also administered to other male dogs and followed by 24-hour observation. Another male dogs with normal response to human chorionic gonadotropin (hCG) were orally administered with 10 mg KCZ/ kg of body weight and (30 mg KCZ /kg of body weight, respectively. Thereafter, the effects of different-dose KCZ on male dog's testosterone production and its response to hCG stimulation were also investigated. The results indicated that KCZ inhibited the conversion from progesterone to testosterone and cortisol in male dogs. Meanwhile, KCZ exerted temporary inhibition on testosterone biosynthesis within 24 hours in male dogs. In addition, the significant difference between dosages on the effects of KCZ treatment on testosterone secretion in male dogs was observed. However, the effect of KCZ treatment on testosterone response to hCG stimulation between dosages was not significant. Moreover, the effects of KCZ on secretion of progesterone and cAMP in MA-10 cells were investigated in vitro. These data indicated that KCZ induced the inhibition of a catalytic component of adenylate cyclase holoenzyme in MA-10 cells. Excepting the selective inhibition of cytochrome P-450 enzymes and competitive binding of androgen receptors by KCZ, we concluded the block of adenylate cyclase activity by KCZ was another possible mechanism to inhibit testicular testosterone secretion.
URI: http://hdl.handle.net/11455/12637
顯示於類別:獸醫學系所

文件中的檔案:
沒有與此文件相關的檔案。


在 DSpace 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。