Differential regulation of heme and drug metabolism in rat testis and prostate: response to cis-platinum and human chorionic gonadotropin.
In the absence of notable changes in heme metabolic activities in the testes of rats treated with cis-platinum (7 mg/kg i.v.) and sacrificed after 1, 3 or 7 days, time-dependent decreases in the activity of benzo(a)pyrene hydroxylase (AHH), ethoxyresorufin O-deethylase (7-ERDE) and the concentration of cytochrome P-450 were observed. In contrast, in the prostate of the treated rats, despite reductions in the activity of heme oxygenase and that of enzymes of heme biosynthetic pathway, biotransformation of benzo(a)pyrene and ethoxyresorufin and cytochrome P-450 concentration were not altered. cis-Platinum treatment (7 days) also decreased markedly the serum and testicular testosterone levels (50-70%). Human chorionic gonadotropin (hCG, 25 IU/100 g/day for 7 days) given to the treated rats (7 days) caused a 5- to 15-fold increase in the serum and testicular testosterone levels and reversed the spectrum of the aforementioned inhibitory effects of cis-platinum on heme metabolic enzymes. The response of the testis and prostate drug metabolic activities to hCG treatment also differed. In the testis of cis-platinum-treated rats, the inhibited AHH and 7-ERDE activities were reversed by hCG treatment and cytochrome P-450 concentration returned to the control level. In the prostate, however, hCG treatment neither changed AHH and 7-ERDE activities nor the concentration of the microsomal cytochrome P-450. In addition, in the testis the pattern of response of AHH and 7-ERDE activities to hCG was dissimilar; whereas 7-ERDE activity returned to the normal level, AHH activity surpassed the normal activity and reached a near 2.5-fold increase over the control value.(ABSTRACT TRUNCATED AT 250 WORDS)
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University of Rochester School of Medicine, Department of Biophysics, New York.
Maines
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D000624:5-Aminolevulinate Synthetase / Q000032:analysis; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis; D008297:Male; D010088:Oxidoreductases / Q000032:analysis; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D006063:Chorionic Gonadotropin; D004364:Pharmaceutical Preparations; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase; D002945:Cisplatin