The sex differences in the hepatic metabolism of imipramine and lidocaine were studied in relation to the effect of gonadectomy and hypophysectomy on these differences. It was found that gonadectomy in male animals led to a more feminine pattern of metabolism. Hypophysectomy mimicked this effect except in the case of lidocaine N-deethylation which was unaffected by hypophysectomy. Castration/hypophysectomy gave a similar result to hypophysectomy alone. These data indicate a gonadal control of metabolism in the male, except for lidocaine N-deethylase, which is under more complex control via the pituitary gland. In the female, ovariectomy was without effect while hypophysectomy caused a masculinization of hepatic metabolism, indicating a dominant role of the pituitary in the control of drug metabolism in the female. This agrees well with reports of hepatic steroid metabolism and lends further support to the hypothesis of a pituitary 'feminizing factor' secreted by the female. The nature of the 'feminizing factor' is, as yet, unknown.
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