The effect of estrogen on monoamine systems in the fetal rat brain.

The effect of a pharmacologic dose of estrogen on brain monoamine systems in the rat fetus was determined using a semiquantitative measure of histofluorescence. Pregnant rats received a subcutaneous injection of cottonseed oil alone or estradiol (E2) in cottonseed oil just before the monoamine systems began to develop. The fetuses were delivered abdominally and killed on day 22 of gestation. A study of four major monoamine areas of the brain with a glyoxilic acid preparation showed that intrauterine exposure to E2 has a significant effect on the monoamine organization of the fetal hypothalamus. No treatment effects were noted in the areas of locus coeruleus, substantia nigra and corpus striatum. The litter sizes of the E2-treated rats and the body weights of the fetuses were much lower than those of the control group. The effect of E2 on monoamine distribution in the fetal hypothalamus may explain the reported disturbances of reproductive function and sexual behavior seen after perinatal exposure to high doses of estrogen in humans.