The Interference of Aroclor 1254 with Progesterone Metabolism in Guinea Pig Adrenal and Testes Microsomes

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Abstract
The effects of Aroclor 1254 on cytochrome P‐450‐mediated steroidogenic activities were investigated in adrenal and testis microsomes of male guinea pigs. A significant decrease was recorded in the tissue content of adrenal microsomal cytochrome P‐450 as well as a significant reduction in the overall conversion of progesterone to steroid products., The effects of exposure to Aroclor 1254 on activities of cytochrome P450 21‐hydroxylase and cytochrome P450 17α‐hydroxylase /C17,20‐lyase were selective. Cytochrome P‐450 21‐Hydroxylase activity was inhibited, as reflected by a decrease in production of 11‐deoxycortisol and 11‐deoxycorticosterone, whereas the cytochrome P‐450 17α‐hydroxylase / C17,20‐lyase activities, represented by the production of 17α‐hydroxyprogesterone and androstenedione were elevated. The same and even more pronounced pattern of altered progesterone metabolism elicited by Aroclor 1254 was observed in vitro, when Aroclor 1254 was introduced into incubation mixtures prepared with adrenal microsomes from untreated animals. Under such experimental conditions, a decrease in the overall metabolism of progesterone was observed as well as a decrease in cytochrome P‐450 21‐hydroxylase activity, while there was significant elevation in the 17α‐hydroxylase /C17,20‐lyase activities.The effect of Aroclor 1254 on the testes differed largely from its effect on the adrenal cortex. In testis microsomes, pretreatment with Aroclor 1254 resulted in no changes in the cytochrome P‐450 content, contrary to the decrease observed in adrenal microsomes. In contrast to its inductive effect on the normally suppressed androgen producing pathway in adrenal microsomes, Aroclor 1254 had no effect on the 17‐hydroxylase /C17,20‐lyase activities in testis microsomes, both in the pretreated animals as well as when it was present in the incubation mixtures containing microsomes of untreated animals. The results of this study indicate a difference in the response of steroidogenic tissues to Aroclor 1254. In adrenal microsomes Aroclor 1254 may have modulated the steroidogenic activities at a posttranscriptional level, possibly by interfering with membrane regulation of these metabolic activities. At the same time, the results obtained do not exclude the possibility that Aroclor 1254 alters the composition of cytochrome P‐450 isozymes present in adrenal tissue.

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