EPIDERMAL GROWTH-FACTOR IN MICE - EFFECTS OF ESTRADIOL, TESTOSTERONE AND DEXAMETHASONE

To clarify the influence of steroids on the metabolism of epidermal growth factor, we studied the effects on its concentrations in adult male and female mice of 1. gonadectomy, 2. postgonadectomy treatments with estradiol and testosterone, and 3. treatment with dexamethasone. We also measured its mRNA levels in submandibular salivary glands and kidneys after ovariectomy. After gonadectomy, the male mice had 1.4-fold higher mean epidermal growth factor concentration in the urine than the female, in contrast to a 1.5-fold reverse difference in intact mice; the female mice had 2.5-fold higher concentration in the submandibular glands than the male animals, in contrast to a 4.5-fold reverse difference in intact mice. The kidney sex difference of intact mice (male > female) was abolished. In both gonadectomized sexes, treatment with testosterone increased the concentration of epidermal growth factor in plasma and the submandibular gland; treatment with estradiol increased the concentration in urine and decreased it in the submandibular gland. Treatment with dexamethasone decreased the concentration of epidermal growth factor in plasma of the male mice, and in urine of the female mice, thus decreasing the sex differences. In the submandibular gland and the kidneys, dexamethasone increased the concentration. The mRNA levels were higher in the submandibular gland and lower in the kidneys in the ovariectomized than in the intact female mice. The effects of sex steroids on epidermal growht factor concentrations are mediated through modulations of its gene activity. Testosterone has an increasing and estradiol a decreasing effect in the submandibular gland. Estradiol has also an increasing effect in the kidneys.