Time- and Dose-Dependent Effect of Triiodothyronine on Submaxillary Gland Epidermal Growth Factor Concentration in Adult Female Mice*

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Abstract
Previous studies have shown that thyroid hormones induced cytodifferentiation in immature and mature mouse submaxillary gland (SMG) and increase SMG concentrations of nerve growth factor and epidermal growth factor (EGF). These observations suggested that thyroid hormones increased SMG EGF synthesis. The following experiments were performed in order to determine the presence of specific nuclear T3 receptors in mouse SMG and the time and dose dependency of the SMG EGF response to a single injection of T3. In the first series of experiments, the presence of specific nuclear T3 receptors was established. The Ka of the receptor in SMG [0.60 ± 0.04 × 1010 M1 (mean ± SEM)] was similar to that observed in liver. The number of binding sites in SMG (46 ± 1 fmol/mg protein) was significantly less than in liver (266 ± 40 fmol/mg protein; P < 0.001). Induction of hypothyroidism in adult female mice by the administration of 0.1% propylthiouracil in their drinking water, led to a significant increase in the number of T3 binding sites (P < 0.01) but had no demonstrable effect on the Ka. These observations suggest significant modulation of T3 receptor number by T3 in mouse SMG. In a second series of experiments, the SMG EGF response to a single ip injection of T3 (100 μg/100 g BW) was examined as a function of time. The dose of T3 employed was calculated to saturate the SMG T3 receptors for approximately 24 h. Euthyroid mice were killed at 24-h intervals for 168 h after T3 injection. SMG EGF concentration was measured by a specific double antibody RIA. In control mice EGF concentrations remained stable for approximately 48 h after T3 injection (0.68 ± 0.19 μg/ng protein). Thereafter, the mean SMG EGF concentration increased progressively to attain a peak concentration of 4.68 ± 1.09 μg/mg protein at 96 h with a t½ of appearance of 69.6 h. After 96 h, SMG EGF concentrations decreased through 168 h with a t½ of disappearance of 29.9 h. In two additional experiments, the t½ of appearance was 72.1 and 76.4 h in euthyroid and hypothyroid animals, respectively. Finally, hypothyroid adult female mice received injections of increasing doses of T3 (1–1000 μg/100 g BW) and killed 96 h later. Maximal SMG concentrations were observed with 500–1000 μg T3/100 g BW (8.99 ± 1.55 μ/mg protein). The ED50 was 60 μg T3/100 g BW. Thus, specific nuclear T3 receptors are present in the SMG of adult female mice. T3 administration results in a time- and dosedependent increase in SMG EGF concentration. The data are consistent with the hypothesis that thyroid hormones increase SMG EGF synthesis. The SMG may therefore be an interesting model for the study of thyroid hormone action.