Effect of thyroid hormone on epidermal growth factor-like immunoreactivity and growth velocity in cynomolgus monkeys

To examine the potential role of epidermal growth factor (EGF) in mediating the effects of thyroid hormone on linear growth, we measured serum EGF levels by RIA in cynomolgus monkeys before and during methimazole-induced hypothyroidism, and after 9 weeks of T4 replacement at different doses. Ten castrated prepubertal monkeys were rendered hypothyroid by methimazole (0.0125% in drinking water for 12 weeks). Methimazole was continued, and T4 was then administered for 9-week intervals. Six weeks elapsed between successive T4 doses. The sequence of different T4 doses for each animal was random. Serum EGF level was measured at baseline and at the end of each treatment period with a newly developed RIA using a polyclonal antiserum against human recombinant EGF. Serum EGF level correlated significantly with the level of serum thyroxine but not with serum triiodothyronine, over the thyroxine dosage range of 1-4 micrograms/kg/day (r = 0.41, p less than 0.005). Lower-leg growth rate correlated significantly with serum EGF level over this same thyroxine dosage range (r = 0.41, p less than 0.005). These data are consistent with the hypothesis that EGF may mediate some of the effects of thyroid hormone on skeletal growth.