A differential effect of thyroxine and glucocorticoids on fetal brain and heart insulin receptor

We investigated the effect of thyroxine (T4), glucocorticoids, and T4 + glucocorticoids on the maturation of fetal rabbit brain and heart insulin receptors. Five doses of T4 over 10 days (50 micrograms/kg body weight per dose) were administered to the mother; significant amounts crossed the placenta (fetal serum free T4 = 0.75 +/- 0.08 versus a control of 0.21 +/- 0.02 ng/dl, p less than 0.02) and increased the specific binding of [125I]insulin to 30-day-old fetal heart membranes from a control of 3.6 +/- 0.74% per 100 micrograms protein to 5.8 +/- 0.19% (p less than 0.05). Curvilinear Scatchard plots revealed an increase in receptor number X 10(7) micrograms protein-1 from 137 +/- 4 to 244 +/- 39 (p less than 0.05) with no change in receptor affinity. No appreciable alteration by T4 in the [125I]insulin-specific binding and receptor number of 30-day fetal brains was noted. Fetal heart glycogen content was decreased and there was a small increase in plasma glucose concentration in the T4-treated group (each p less than 0.02). Betamethasone at 0.17 mg/kg did not affect the specific binding of [125I]insulin to 27-day fetal heart or brain plasma membranes, although a decrease in heart glycogen content and an increase in plasma glucose concentration were observed (each p less than 0.02). Also T4 + betamethasone did not alter the [125I]insulin binding to 27-day fetal heart or brain plasma membranes, but resulted in an additive effect (a marked depletion) on cardiac glycogen (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)