Estrogen receptors in the rhesus monkey brain during fetal development

Abstract

Estrogen receptor (ER) levels were measured in brain tissue cytosol from fetal male and female rhesus monkeys at Days 70, 100 and 160 postconception. The brain regions which were examined included medial basal hypothalamus (MBH), amygdala (AMG), cerebral cotex (CTX) and cerebellum (CB). For comparison, brain tissues were also obtained from an adult female, and muscle (MUS) and genital tract (GEN, ovaries + uterus) ER values were measured in several Day 70 fetuses. Tissues were dissected and homogenized as previously described 24. Cytosol was passed through a microcolumn of Lipidex 1000 to remove interfering lipids and incubated with [ 3H]Moxestrol (4 nM) in the presence or absence of 500 nM Moxestrol. Incubations were carried out for 24 h at 4 °C, and free and bound ligand separated by Sephadex LH-20 gel filtration. In one case (Day 160 male fetus), saturation analysis yielded an estimate of apparent K d of 0.46 × 10 −9M and indicated that maximal specific binding was achieved at a ligand concentration of 1–2 nM. There was no sex difference at any stage of development (ANOVA). A significant age effect ( P < 0.002) was noted for the MBH and CB but not for any of the other tissues examined. In the MBH the significance of this effect was due to a progressive increase in ER levels with fetal age and into adulthood. In contrast, CB levels exhibited a progressive decline with age. These studies revealed that the ER is present during brain development. Thus any estrogens derived from the aromatization of circulating fetal androgens could potentially exert an influence upon brain differentiation, particularly upon the MBH at late gestation and adulthood. The lack of a definitive sex difference suggests that both sexes are potentially susceptible to estrogen modification. However, this susceptibility may be minimal, since receptor concentrations are considerably lower than values reported in the literature for postnatal monkeys.