The regulation by thyroid hormones and androgen of epidermal growth factor synthesis in the submandibular gland and its plasma concentrations in mice

The effects of androgen and thyroid hormones on epidermal growth factor (EGF) synthesis in the submandibular gland and on plasma EGF concentrations in mice were examined. Testosterone propionate was administered alone or in combination with L-thyroxine (T4) to female mice for 2 weeks. The submandibular EGF concentrations were increased by the administration of testosterone propionate in a dose-dependent fashion; the maximal increase, 20-fold, being produced by a dose of 2 mg every other day. The EGF levels were increased sevenfold by T4, which also enhanced the stimulatory effect of suboptimal doses of testosterone propionate. Cyproterone acetate, an anti-androgen, inhibited the testosterone propionate-induced increase, but not the T4-induced increase. Plasma EGF concentrations were raised by testosterone propionate but not by T4. Both hormones stimulated the accumulation of 4.7 kb preproEGF mRNA in the submandibular gland, which occurred almost in a parallel manner with the increase in submandibular EGF concentrations. These results suggest that EGF synthesis in the submandibular gland is regulated by alterations in the level of its mRNA by thyroid hormones and androgen, and that the rise in plasma EGF concentrations is under the influence of androgen but not of thyroid hormones.