Effect of perinatal methimazole exposure on enolase isozymes in the developing rat.

The induction of hypothyroidism by methimazole produces a delay in CNS development as well as behavioral deficits in rat pups. Methimazole (0.1 mg/ml) was administered via drinking water to dams from gestational day 17 to postnatal day 10. Rat pup body weight was reduced on postnatal day 15 (P15) and 30 (P30) while brain weight was decreased only at P15. Soluble brain protein was decreased at P15 and P30. Total enolase and neuron-specific plus hybrid enolase (NSE+H) specific activity and activity were reduced on P15, while non-neuronal enolase (NNE) activity but not specific activity was depressed. At postnatal day 30, total enolase and NSE+H activity were slightly reduced, but NNE activity and the specific activities of total enolase, NNE and NSE+H were similar to controls. The ratio of NSE+H to NNE was reduced at P15 but not P30. The alterations in enolase activity following methimazole administration suggest a delay in the development and maturation of the CNS at P15. These results provide a biochemical correlate of the developmental delays reported in hypothyroid rat pups.