The use of the fetal and neonatal mouse to study the effects of steroidal and nonsteroidal substances on development and carcinogenesis has a long history. Since the early 1960s, this animal model system has been exploited by several groups throughout the world, and it is useful to recount some of the more significant points in this history. I shall also point out areas of inquiry where the mouse model continues to be used in a search for the fundamental nature of the processes by which steroid hormones cause permanent effects during development, with the hope that some of those experiments may provide clues to the causes of present or yet unseen situations in the human.
Early studies1,2 showed vaginal and cervical tumor formation in adult mice treated with estrogens in the newborn period. As early as 1963, concern was expressed about the possibility of similar consequences in humans who might be exposed to hormonal substances early in development. Subsequent investigations2-4 showed that administration of estrogen and androgen to newborn female mice in the first five days of life led to permanent vaginal and cervical changes in the adult, which were in many cases (depending on the dose administered) ovary independent; that is, the changes persisted after ovariectomy of the animal at day 40. Studies on the vaginal tissues of the adult animals that had been treated with steroids in the newborn period showed that there were permanent alterations of rates of DNA, protein, and RNA synthesis in those tissues, and that those changes apparently occurred with out modification of the fundamental characteristic of specific binding of estrogen by the vagina.3
Analytical Methods for the Determination of Neuroactive Steroids
