The effects of sex and neonatal androgenization on thymidine kinase activity and DNA content in the cerebellum of the rat

Abstract

The effects of neonatally administered testosterone propionate (TP) were determined on the activity of thymidine kinase and on the content of DNA in the cerebellum of the rat during early postnatal development. Forty-eight hiours after birth, female and male pups were injected s.c. with either 1.5 mg TP or an equivalent volume of vehicle. Cerebellar thymidine kinase activity and DNA content were measured at 3, 4, 6, 7, 8, 10, 12, 15, 18 and 21 days of age. A sexual dimorphism in thymidine kinase activity was found for control rats between 6 and 18 days of age, i.e. the activity of the enzyme was significantly higher in the cerebellum of the female controls. The activity of thymidine kinase in the cerebellum of TP-treated male rats was significantly greater than that of the male controls between 4 and 21 days of age. The activity of thymidine kinase in the cerebellum of TP-treated female pups was significantly lower than that of the female controls between 6 and 12 days of age. Enzyme activity at age 15 days was the same for TP-treated and control female rats. However, thymidine kinase activity in the cerebellum at TP-treated female ratswas significantly increased above that of the controls at 18 and 21 days of age. Thus, the response of the enzyme following the injection of TP 48 h after birth was sex-dependent between 4 and 15 days of age. Alterations in cerebellar DNA content in the TP-treated male and female rats closely paralleled the changes described for thymidine kinase. These data suggest sex-dependent transactions between the animal and the injection of TP as well as androgen-dependent relationships between thymidine kinase and DNA synthesis in the cerebellum. Significant changes in the Michaelis-Menten constant with increasing age also suggest that the developing cerebellum contains more than one form of the enzyme.