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J.Health Sci., 51(3), 369-375, 2005
In Vitro Inhibitory Effects of Cannabinoids on Progesterone 17alpha-Hydroxylase Activity in Rat Testis Microsomes
Tatsuya Funahashi,a Hideharu Ikeuchi,a Satoshi Yamaori,a Toshiyuki Kimura,a Ikuo Yamamoto,b and Kazuhito Watanabe*, a
aDepartment of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan and bDepartment of Hygienic Chemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino-machi, Nobeoka, Miyazaki 882-8508, Japan
The inhibitory effects of three major cannabinoids [Delta9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN)] contained in marijuana, an abused drug, on progesterone 17alpha-hydroxylase activity in rat testis microsomes were investigated. Microsomal progesterone 17alpha-hydroxylase activity was significantly inhibited in the presence of more than 50 mu M of Delta9-THC and CBN compared with control activity, and the IC50 values for Delta9-THC and CBN were estimated to be 42.8 and 32.9 mu M, respectively. CBD showed less but significant inhibitory effects on 17alpha-hydroxylase activity at concentrations greater than 100 mu M, and the IC50 value for the cannabinoid was estimated to be 290.9 mu M. Kinetic analysis using double reciprocal plots showed that the type of inhibition by CBN was competitive, whereas that of Delta9-THC and CBD was the mixed type. These results suggest that the inhibition may be due to metabolic interactions between each cannabinoid and 17alpha-hydroxylase.
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