RESUMEN
The capacity of the testis to metabolize xenobiotics has been proposed to play a role in the susceptibility of different species to testicular toxicity. Since species differences in testicular xenobiotic metabolizing enzyme activities are not well documented, the primary objective of the present study was to compare enzyme activities in subcellular fractions prepared from rat, mouse, monkey, and human testes. In microsomal fractions, enzyme activities measured were pentoxyresorufin O-dealkylase (PROD), ethoxyresorufin O-dealkylase (EROD), and epoxide hydrolase (mEH). In cytosolic preparations, epoxide hydrolase (cEH) and glutathione S-transferase (cGST) activities were measured. PROD activity was not detectable in any of the species studied, while it was readily detected in liver microsomes used as a positive control. Although EROD activity was low, it was measurable in testicular microsomes from rat and mouse, but not monkey or human. No marked species differences in cEH activity were found. In contrast, mEH activity was low in the monkey, intermediate in the rat, and highest in the human and mouse. cGST activity was significantly lower in the two primate species compared with the rat and the mouse. The levels of activity of the xenobiotic metabolizing enzymes studied were generally more than an order of magnitude lower in the testis as compared to the liver. However, in rat and mouse, the levels of mEH and cGST activities in testis were relatively similar to hepatic levels. Overall, these data indicate that species differences in capacity to metabolize xenobiotics may play a role in differential sensitivity to testicular toxicants.
Asunto(s)
Testículo/enzimología , Xenobióticos/metabolismo , Adulto , Animales , Citocromo P-450 CYP1A1 , Citocromo P-450 CYP2B1 , Sistema Enzimático del Citocromo P-450/metabolismo , Citosol/enzimología , Citosol/metabolismo , Epóxido Hidrolasas/metabolismo , Glutatión Transferasa/metabolismo , Humanos , Técnicas In Vitro , Macaca mulatta , Masculino , Ratones , Ratones Endogámicos , Microsomas Hepáticos/enzimología , Oxidorreductasas/metabolismo , Ratas , Ratas Endogámicas F344 , Especificidad de la Especie , Fracciones Subcelulares/metabolismoRESUMEN
Testicular toxicants have become of increasing importance necessitating a better understanding of the possible role of testicular xenobiotic metabolism. The responsiveness of testicular microsomal epoxide hydrolase (mEH), cytosolic epoxide hydrolase (cEH), and cytosolic glutathione S-transferase (cGST) to hepatic inducers was studied in sexually mature male F344 rats and CD-1 mice. The hepatic inducers employed were phenobarbital (PB), beta-naphthoflavone (BNF), and butylated hydroxyanisole (BHA) which are known to induce cytochrome P-450, cytochrome P-448, and cGST, respectively. Hepatic mEH, cEH and cGST activities were assessed as positive controls. Measurable activities of all enzymes studied were present in the testes of both rats and mice. PB, BNF, and BHA produced the expected effects on mEH, cEH, and cGST in rat and mouse livers, whereas the testes were generally nonresponsive to the inducers. Induction of testicular cGST by PB occurred in mice but not rats and was the only testicular effect produced by the hepatic inducers in this study.