The influence of peripubertal exposure to physiological levels of testosterone on the adult androgen responsiveness of the cytochrome P450 enzyme activity, hepatic microsomal erythromycin demethylase activity, was investigated.
Rats were injected subcutaneously with testosterone enanthate 5 µmoles/kg/day either peripubertally, during adulthood or in both time periods. In adult untreated rats, hepatic microsomal erythromycin demethylase activity was higher in males than in females. Intact adult male rats, but not intact adult female rats, responded to adult testosterone treatment with an increase in hepatic microsomal erythromycin demethylase activity.
Female and male rats were gonadectomized before the onset of puberty. In the adult female rats which had been prepubertally ovariectomized, exposure to testosterone peripubertally resulted in an adult androgen responsiveness for hepatic microsomal erythromycin demethylase activity. This indicated that the potential is present in the prepubertally ovariectomized female rat for the pubertal imprinting by testosterone of an adult androgen responsiveness for hepatic microsomal erythromycin demethylase activity.
Prepubertal castration of male rats reduced hepatic microsomal erythromycin demethylase activity and plasma testosterone levels from control levels. Hepatic microsomal erythromycin demethylase activity was found to be partially correlated with plasma testosterone levels. The higher hepatic microsomal erythromycin demethylase activity in the adult male rat may therefore be related to high adult male levels of circulating testosterone. The administration of testosterone to adult male rats which had been prepubertally castrated resulted in hepatic microsomal erythromycin demethylase activity which was lower than that of intact males and of intact males treated with testosterone in adulthood. These results indicated that adult androgen responsiveness of hepatic microsomal erythromycin demethylase activity is not completely imprinted in male rats in the neonatal period.
This study provided evidence in support of the hypothesis that the peripubertal period is a time during which imprinting by testosterone of adult androgen responsiveness of hepatic P450 enzymes can occur. / Pharmaceutical Sciences, Faculty of / Graduate
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/28935 |
| Date | January 1989 |
| Creators | Cadario, Barbara Jane |
| Publisher | University of British Columbia |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
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