The development of estrogen receptor systems in the rat brain: perinatal development

The estrogen receptor system of the rat brain is not detected at 15 and 19 days of gestation, even though estrogen receptors can be measured in the maternal hypothalamus. Estrogen receptors are first detected around the 21st day of gestation after which they increase rapidly in the perinatal period and reach a plateau around postnatal day 6. Estrogen receptors are found predominantly in the limbic brain (hypothalamus, preoptic area, amygdala) and in the cerebral cortex, and they are present in very low levels in a sample consisting of the midbrain, brain stem and cerebellum. Development of cortical estrogen receptors is retarded by a few days compared to those in the limbic brain, but then is extremely rapid so that cortical receptor levels are equal to those in the limbic block on or about postnatal day 6. As early as estrogen receptors can be detected in the fetus (day 21 of gestation), they are occupied by endogenous estradiol in male but not in female fetuses. This is measured by the occurrence of cell nuclear estrogen receptor complexes which can be detected by an exchange assay. The presence of such complexes in male limbic brain tissue is consistent with the presence of testicular androgen in the circulation and with the existence in the brain of aromatizing enzymes capable of converting testosterone to estradiol. The absence of such complexes from the female limbic brain is consistent with the protective role of alpha-fetoprotein in scavenging circulating maternal estradiol and keeping it from reaching intracellular receptor sites. The results are discussed with respect to the timing of the critical period for brain sexual differentiation and related maturational events.