Sex differences in the development of estrogen receptors in the rat brain.

The mechanisms involved in sexual differentiation of the brain remain incompletely defined. In mammals, testosterone secretion by the male during early development permanently alters the capacity of the brain to respond to circulating estrogen. In rats, this change in estrogen responsiveness is associated with a reduction in estrogen receptor (ER) levels in the periventricular region of the preoptic area (PVP), the medial preoptic nucleus (MPO), and the hypothalamic ventromedial nucleus (VMN) of the male. To determine whether these differences represent a response to early testosterone exposure or a secondary consequence of gonadal secretions at puberty, ER levels were measured by quantitative in vitro autoradiography in the brains of rats killed at intervals between 1-10 and 28-49 days of age. As early as 24 hr after birth, ER sex differences in the MPO and PVP are already quantitatively similar to those observed in adulthood. A sex difference in the VMN emerges later, between 5 and 10 days of age. Differences between brain regions are also observed in the rate of ER development after the first week of life, ER concentrations in the PVP and MPO being close to adult levels within 1 day of birth, in contrast to the VMN where they increase markedly between Day 10 and adulthood in both sexes. These observations suggest that changes in ER concentrations may be one of the earliest hallmarks of brain sexual differentiation. Sex differences in ER in different brain regions may, however, be expressed asynchronously, providing a possible mechanism for variation in the duration of "critical periods" for testosterone-mediated organization of specific CNS functions.