Altered thyroidal states modulate the insulin receptor characteristics of the developing rabbit brain

We investigated the effect of propylthiouracil (PTU)-induced hypothyroidism and T4-induced hyperthyroidism on the fetal and neonatal rabbit brain insulin receptors (number and affinity) using plasma membranes. PTU administration to the pregnant mothers resulted in low serum-free T4 and normal total T3 concentrations, while T4 therapy to the mothers resulted in high serum-free T4 and high total T3 concentrations in the fetus and neonate. PTU-induced hypothyroidism did not affect the fetal brain insulin receptors, cholesterol content (brain homogenate) or protein content. On the other hand, brain insulin receptor number and total brain cholesterol content decreased in the neonate. T4 therapy at 100 micrograms/kg reversed the serum T4 to the control value and normalized the neonatal brain insulin receptor number and cholesterol content while a higher dose of T4 (200 micrograms/kg) increased the neonatal brain insulin receptor number, cholesterol and protein content. We conclude that altered thyroidal states modulate the brain insulin receptor (number and affinity) in neonatal, but not fetal brain plasma membranes.