Thyroxine increases submandibular gland nerve growth factor and epidermal growth factor concentrations precociously in neonatal mice: Evidence for thyroid hormone-mediated growth factor synthesis

Abstract

Thyroxine (T4) administration to adult female mice significantly increases submandibular gland (SMG) nerve growth factor (NGF) and epidermal growth factor (EGF) concentrations and does so in a time- and dose-dependent manner. Postnatal maturation of the SMG can be markedly accelerated by T4 treatment. We, therefore, performed a series of experiments to examine the effect of T4 on SMG NGF and EGF content and concentration as a function of postnatal age in neonatal mice. In experiment 1, male and female neonatal Swiss-Webster mice received daily subcutaneous injections of T4 (0.4 μg/ g body weight) for 6, 13, or 20 days and were sacrificed 24 h after the last injection. Vehicle injected mice served as controls. SMG NGF and EGF content and concentration were measured by specific double antibody radioimmunoassay systems. Pools were made using either female or male SMGs. Since no significant differences were noted for NGF or EGF content using sex of the animal as the determining variable, the values were combined. At 7 days of age, mean SMG NGF and EGF content and concentration of control mice significantly exceeded those of T4-treated animals (p < 0.05). At 14 days of age, mean SMG NGF and EGF content in T4-treated mice significantly exceeded those in control mice by 39- and 22-fold, respectively (p < 0.001). At 21 days of age, these increases were 4100- and 2400-fold, respectively. In order to determine more precisely the time of onset of responsivity of the SMG to thyroid hormones, a second series of experiments was performed. Vehicle and T4 (0.4 μg/g body weight daily) injected mice were sacrificed at 7, 9, 11, and 14 days of age. SMG EGF concentration was measured by radioimmunoassay. T4 treatment was without significant effect at 7 and 9 days of age. At 11 days of age, mean SMG EGF content and concentration in the T4-treated mice exceeded that in control mice by a factor of 2 (p < 0.05). Subsequently, SMG EGF content and concentration increased exponentially. Daily treatment of neonatal mice from birth or from the 7th postnatal day resulted in similar SMG EGF content and concentration when measured at 14 days of age. These data indicate that T4 administration to neonatal mice significantly increases SMG NGF and EGF concentrations and markedly accelerates their appearance in the gland as early as 11 days of age. Onset of SMG EGF responsiveness to thyroid hormone appears to commence at some time on or after the 7th postnatal day. The observation of exponential increases in SMG growth factor concentrations strongly suggest thyroid hormone mediated synthesis. The use of the neonatal SMG as a model will allow further insights into the biosynthesis of NGF and EGF and also into the mechanism of thyroid hormone action. © 1986 International Pediatric Research Foundation, Inc.