ブタ精巣ミクロソームに存在する△^<16>-C_<19>-ステロイド合成活性及び17α-ヒドロキシラーゼ/リアーゼ活性に及ぼすKetoconazole及び各種ステロイドの阻害効果

概要

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The inhibitory effects of ketoconazole and various steroids against Δ^<16>-C_<19>-steroid synthesizing activity and 17α-hydroxylase activity in testicular microsomes of neonatal pig were investigated. Against these two enzyme activities in microsomes ketoconazole showed a concentration-dependent inhivitory effect and 50% inhibition concentration against the above two enzyme activities was about 0.6μM. Moreover, various steroids had a similar inhibitory effect against both of these activities, and 20α-hydroxypregn-4-en-3-one and 20β-hydroxypregn-4-en-3-one showed strong inhibitory effects. In the reconstitutional system consisting cytochrome P-450 (17α-hydroxylase/lyase), P-450 reductase, cytochrome b_5,ketoconazole or 17α-hydroxyprogesterone showed similar inhibitory effects against these two enzyme activities. The inhibition constants (K_i) of ketoconazole to Δ^<16>-C_<19>-steroid synthesizing activity and 17α-hydroxylase/lyase were 0.22μM and 0.11μM, respectively. On the other hand, the K_i values of 17α-hydroxyprogesterone against the both activities were 15.7μM and 11.6μM, respectively.
公益社団法人日本薬学会の論文
1987-01-25