Neonatal hyperthyroidism alters submandibular gland epidermal growth factor response to thyroxine in the adult mouse

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 microgram 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 less than 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 less than 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 micrograms/d) of adult mice, SMG weight in NH mice increased significantly (P less than 0.01) but was unchanged in control mice. SMG EGF content and concentration increased significantly in both adult NH and control mice (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)