Neonatal hyperthyroidism (NH) in the rat is associated with permanent reductions in serum thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations in the adult, changes suggestive of a hypothyroid state. In the adult NH rat, the thyrotroph appears to be more sensitive to the feedback effects of thyroid hormones. To determine whether thyroid hormone sensitive tissues retain their responsiveness to thyroid hormones, the long-term effects of NH on mouse submandibular gland (SMG) epidermal growth factor (EGF) content were examined. NH was induced in female mice by 20 daily subcultaneous injections of 0.4 μg of T4 per gram of body weight. Control female mice received daily injections of vehicle alone. At 21 days of age, NH and control mice were sacrificed and SMG EGF content was measured by specific radioimmunoassay. SMG EGF content and concentration in 21-day-old NH mice exceeded that of control mice by 2400- and 1500-fold, respectively (P < 0.001). SMG EGF content and concentration in adult (90-day-old) NH mice were slightly, but not significantly, lower than those of control mice. Mean SMG weight, however, was significantly decreased in adult NH mice (P < 0.01). Interestingly, SMG content and concentration of EGF in adult NH mice were lower than in 21-day-old NH mice. After 5 days T4 treatment (16 μg/d) of adult mice, SMG weight in NH mice increased significantly (P < 0.01) but was unchanged in control mice. SMG EGF content and concentration increased significantly in both adult NH and control mice (P < 0.01). However, the magnitude of the increase was markedly obtunded in adult NH mice. These observations indicate that thyroid hormones precociously and exponentially increase SMG EGF content and concentration in neonatal mice. The marked increases strongly suggest thyroid hormone mediated synthesis of EGF and acceleration of maturation of gene expression for EGF synthesis. In addition, NH appears to modify thyroid hormone regulation of gene expression for EGF synthesis in adult mice.
Stimulation of epidermal growth factor gene expression during the fetal mouse reproductive tract differentiation: role of androgen and its receptor.
