Effect of continuous thyroxine administration on thyrotropin secretion in thyroidectomized rats.

Abstract

We have studied the effect of T4 itself (i.e. without extrapituitary conversion to T3) on the feedback regulation of pituitary TSH secretion in thyroidectomized rats receiving continuous T4 or T3 replacement. Continuous sc infusion of 1.0 or 2.0 microgram T4/100 g . day in 0.01 N NaOH, 20% 1,2-propanediol vehicle failed to maintain the plasma T4 concentration in thyroidectomized rats for more than 48 h, despite the verification of T4 delivery. Continuous sc infusion of 1.0 or 2.0 microgram T4/100 g . day in 0.01 N NaOH, 5% rat serum resulted in a dose-dependent elevation in the plasma T4 concentration and inhibition of the postthyroidectomy rise in plasma TSH, in the presence of low plasma T3 concentrations. Mimicking the low plasma T3 concentrations that resulted from T4 infusion by continuous replacement of 280 ng T3/100 g . day failed to inhibit the postthyroidectomy rise in plasma TSH. The pituitary responsiveness to TRH (250 ng/100 g, iv) after 96 h of thyroid hormone infusion was significantly (P less than 0.05) inhibited only in the group receiving 2.0 microgram T4/100 g . day. These results indicate that the plasma T4, concentration in addition to that of plasma T3, conveys feedback information to the pituitary. With regard to pituitary TSH secretion, T4 acts as both a prohormone giving rise to a protion of the plasma T3 by peripheral monodeiodination and as a hormone conveying feedback information via the blood to the pituitary.