PRENATAL PROGRAMMING OF HEPATIC MONO-AMINE OXIDASE BY 5,5-DIPHENYLHYDANTOIN

During ontogeny, rat liver monoamine oxidase gradually increased in activity in both sexes until the pubertal period when female activity rose 1.5- to 2.0-fold higher than male activity. Oral administration of 5,5-diphenylhydantoin (10 mg/kg body wt) to pregnant rats on days 7,9, 12, 14and 16 of gestation had no effect on the monoamine oxidase activity of immature male or female offspring. The enzyme activity in adult male offspring, from females prenatally treated with diphenylhydantoin, was elevated to a level similar to that of adult females. Subcutaneous injection of diphenylhydantoin (10 mg/kg body wt) for 5 days prior to death failed to induce changes in monoamine oxidase activity in either pre- or postpubertal males or females. Thus, prenatal administration of diphenylhydantoin can program changes in adult male monoamine oxidase activity. The serum levels of testosterone in the male offspring of prenatally treated females, on days 5 and 63 postpartum, were the same as those of their respective controls, demonstrating that the changes caused by diphenylhydantoin are not due to diminished levels of testosterone. © 1979.