ABSTRACT
As early as 1921 C. R. Stockard claimed that there are certain stages in vertebrate ontogeny during which toxic substances have more injurious effects than in adulthood. These stages were referred to as “critical periods”, being evident during organogenesis in mammals. The syndrome resulting from early exposure to sex hormones has been extensively studied in rats, revealing a mechanism of persistent secretion of ovarian estrogen owing to permanent functional alteration of the hypothalamo-hypophysial system. Long-term administration of estrogen in adulthood is known to cause hyperplastic, dysplastic, and neoplastic lesions in the mammary and pituitary glands, kidney, gonad, and accessory organs in male and female rats, mice, and hamsters. Crystals and/or concretions also appear in the vaginal lumen in neonatally Entreated adult mice. There have been few attempts to search for effective factor(s) which can prevent the occurrence of hormone-induced lesions other than a series of experiments with retinoids.
