Long-Term Effects of Neonatal Steroid Exposure on Mammary Gland Development and Tumorigenesis in Mice2

Abstract

Newborn female mice of three strains—BALB/cfC3H [mammary tumor virus (MuMTV)-infected], BALB/c, and C57BL (both virus-free)—were given injections of 17β-estradiol or testosterone, alone or in combination with ovine prolactin, for the first 5 days of life. Half of each group of mice were ovariectomized at 40 days of age, and all mice were killed between 6 and 16 months of age. Mammary glands of BALB/cfC3H mice receiving steroid hormones were better developed than those of mice not receiving steroids. Androgen induced a higher incidence of grossly dilated ducts and secretion-filled alveoli. Mammary nodule and tumor incidences were higher in steroid-treated mice than in controls; androgen resulted in higher incidences than did estrogen. The age of onset of mammary tumors was also earlier after neonatal steroid treatment. In BALB/c mice, neonatal injections of estrogen induced some alveolar development of the mammary gland; neonatal injections of ovine prolactin had a greater effect. The mammary glands of C57BL mice did not show any evidence of stimulation by neonatal hormone treatment, which indicated the probability of strain differences. However, no nodules or tumors occurred in these MuMTV-free strains. Therefore, MuMTV was essential for neoplastic mammary responses to neonatal hormone treatment. Ovariectomy prevented alveolar development and abnormal changes in the mammary glands of all groups, thus indicating that ovary-independent alterations in the mammary gland were not induced by neonatal steroid treatment. We concluded that neonatal steroid exposure resulted in increased mammary tumor risk in mice, but only in the presence of both MuMTV and ovaries.