Molecular and biochemical studies on the species differences of cytochrome P-450 related to forms expressed specifically in respective male and female rats

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In previous studies, we clarified that the occurrence of the sex-related differences in the actions and toxidities of drugs and toxicants could be accounted for by the presence of sex-specific forms of cytochrome P450(P-450-male and P-450-female) inliver microsomes of rats. Thus, the purpose of this research was to examine the possibility of whether are forms of cytochrome P-450 with properties similar to P-450-male in microsomes of other animal species including humans. The function of the forms of cytochrome P-450 was also studied.During the course of this research projects, we obtained results as follows; 1) Proteins immunochemically reactive with anti-P-450-male antibodies were present in liver microsomes of all animals examinned. The activities of hydroxylases of testosterone, varied animal species, indicating that the functions of cytochrome P-450 related to P-450-male were not necessarily identical among animals. 2)In the first evidence that hamster showed significant sex differences in the population of cytochrome P-450 as well as the activities of testosterone hydroxylases. These were regulated by groth hormone. 3)Forms of cytochrome P-450 immunochemically related to P-450-male, which were purified from liver microsomes of beagle dogs, showed drug oxidation activities in a similar fashion but differed with each other in steroid hydroxylations. 4)A cDNA clone with sequences homologous to P-450-male were obtained and expressed in yeast.In conclusion, this research project was completed along with the proposedule, but to much higher extsnts.