Changes in Tissue Concentrations of Thyrotropin, Free Thyrotropinβ, and α-Subunits after Thyroxine Administration: Comparison of Mouse Hypothyroid Pituitary and Thyrotropic Tumors*

Abstract
We have previously demonstrated divergent changes in pituitary free TSHβ and α-subunit concentrations in hypothyroid mice during prolongation of experimental hypothyroidism and after T4 administration. This report compares the simultaneous responses of pituitary and thyrotropic tumor TSH, TSHβ, and a-subunit to 12 days of T4 administration in four groups of hypothyroid LAF1 mice bearing thyrotropic tumors. Half of each group received daily injections of T4 (10 μg/100 g BW, ip) for 12 days; the other half of each group received saline. Plasma concentrations of TSH, free TSHβ, and free α-subunit were suppressed by T4 administration to 0.1–1.5%, 2.0– 3.9%, and 4.1–25% of control concentrations, respectively. Pituitary TSH and free TSHβ concentrations fell significantly with treatment to 24–43% and 10–28% of control concentrations, respectively. In contrast, pituitary α-subunit concentrations did not fall (they were 106–203% of control values), and a rise in the pituitary α-subunit concentration was statistically significant in one group (P < 0.02). Thyrotropic tumor TSH and free TSH/3 concentrations fell significantly with treatment to 9–31% and 8–35% of control concentrations, respectively. Tumor asubunit concentrations did not fall (they were 87–195% of control values), and a 2-fold rise was statistically significant in one group (P < 0.05). Both pituitary and tumor α-subunit to TSHβ molar ratios increased significantly with T4 administration in all groups. We conclude that (1) pituitary and thyrotropic tumor TSHβ concentrations fall after 12 days of T4 administration while α-subunit concentrations are unchanged or actually rise; (2) this divergent response is qualitatively similar in hypothyroid mouse pituitary and thyrotropic tumors; and (3) these data suggest differences between the regulation of intracellular TSHβ and α-subunit.