Long term effects of perinatal injection of estrogen and progesterone on the morphological and biochemical development of the mammary gland.

The effects of neonatal injection of estrogen and progesterone on the subsequent in vitro hormone responsiveness of murine mammary glands were determined by a coordinated study of the morphological development and the biochemical response of explants. After daily in vivo pretreatment with estrogen and progesterone, explants were cultured for 5 days in a chemically defined medium containing insulin alone or insulin, cortisol, and PRL. After the culture period, the morphological development of alveoli and lobules was rated. In addition, casein mRNA was quantitated using a specific complementary DNA hybridization probe. Perinatal 17 beta-estradiol exposure was found to increase casein mRNA content as well as lobular development. Conversely, perinatal progesterone treatment inhibited both casein mRNA induction and the formation of lobules. The administration of both estradiol and progesterone to newborns resulted in an antagonistic response between these two steroids, and there was no effect on casein mRNA levels or lobular development in comparison with untreated controls. Mammary tissues of perinatally estrogen-treate mice displayed greater lobular development and contained higher levels of casein mRNA in response to an extension of the duration of in vivo pretreatment from 6 to 9 days. A comparison of the PRL dose response in vitro suggested that exposure to estrogen perinatally sensitized the mammary tissue to the subsequent addition of PRL in culture. These studies indicate that injection of newborns with estrogen may enhance the subsequent hormonally regulated differentiation of the mammary gland. Exposure to progesterone may inhibit later development, and both steroids in combination may exert antagonistic effects. These effects were not mediated solely by alterations in the normal endocrine status of the treated animals but were reflected by the subsequent hormonal response of mammary explants in a defined culture medium. This altered sensitive to hormones may be important in the increased incidence of mammary dysplasias observed in these animals.