Neonatal feminization of hepatic mono-oxygenase in adult male rats: altered sexual dimorphic response to cadmium
Lui, E.M.; Lucier, G.W.
Journal of Pharmacology and Experimental Therapeutics 212(2): 211-216
1980
ISSN/ISBN: 0022-3565 PMID: 7351633 Document Number: 163112
The effects of exposure of neonates (2, 4 and 6 days after birth) to testosterone propionate (TP) or diethylstilbestrol (DES) on the hepatic mono-oxygenase system of immature and mature rats was studied. Sex-related differences in the hepatic microsomal ethylmorphine N-demethylation activities were seen only in control mature rats; specific activities in males were 4-fold higher than in females. Administration of TP or DES to neonates caused the feminization (depression) of hepatic ethylmorphine N-demethylation activities of adult male rats without significantly altering the enzyme activities in either the mature female rats or immature rats of either sex. Kinetic studies revealed neonatal feminization of Km values for the N-demethylation in adult male rats. Reduction in serum androgen levels of adult male rats was associated with the treatment of neonates with DES but not with TP. No sex differences in hepatic cytochrome P-450 contents were evident in adult rats. Treatment of neonates with hormones did not alter P-450 levels in adult male rats. The age- and sex-dependent response of hepatic mono-oxygenase after exposure of neonates to TP or DES suggests changes in the sexual differentiation of hepatic enzymes in males rats. Reduction of hepatic ethylmorphine N-demethylation activity and cytochrome P-450 contents after Cd treatment (2.0 mg/kg i.p.) was age- and sex-dependent in the rat; marked reduction in enzyme activity was seen only in adult male rats. Adult male rats which had received TP or DES treatments during the neonatal period exhibited decreased sensitiity toward the hepatotoxic effects of Cd, responses in the treated groups were similar to those of females. The apparent feminization of the hepatic response to Cd may reflect both qualitative and quantitative changes in the hepatic mono-oxygenase system in adult male rats resulting from TP or DES exposure during the neonatal period.