Ontogeny of Estradiol-Binding Sites in Rat Brain. I. Appearance of Presumptive Adult Receptors in Cytosol and Nuclei

Abstract

Investigations were made concerning the age at which regionally specific cell nuclear binding sites for estradiol appear in the female rat brain, and the cellular mechanism which might govern their appearance. One hr in vivo uptake of 3H-estradiol into whole tissue homogenates and nuclear pellets was studied at different times after birth in brain regions of ovariectomized female rats. Brain regions known to bind estradiol, namely, hypothalamus-preoptic area-amygdalamidbrain (HPAMB), were compared with cerebral cortex. HPAMB nuclear uptake of 3H-estradiol rose slightly during the first 3 weeks after birth and then increased approximately 6-fold between days 20–24 and 25–26. This high level of HPAMB nuclear uptake of estradiol persisted, with minor quantitative variations, in all subsequent age groups studied. Concentrations of radioactivity in nuclear pellets of cerebral cortex were low throughout development. Radioactivity concentrations in nuclear pellets of HPAMB and, to a lesser extent, cerebral cortex from pre- and postpuberal animals were significantly reduced by concurrent injections of unlabeled 17β-estradiol, indicating the presence of limited-capacity nuclear binding sites for estradiol in both types of brain regions. Competing estradiol also reduced slightly, but not significantly, nuclear uptake of 3H-estradiol in neonatal brains. In vitro3H-estradiol-binding experiments were performed with HPAMB cytosol from rats of different ages, in order to determine whether an increase in concentration of cytoplasmic binding sites might account for the acute maturation of nuclear binding capacity observed in the fourth postnatal week. Despite a progressive rise in in vitro estradiol-binding capacity of HPAMB cytosol during development, no sharp rise in this capacity was detected during the period of major increase in HPAMB nuclear binding capacity. It was concluded that other factors must be responsible for maturation of HPAMB nuclear estradiolbinding sites. The possible involvement of this developmental event in the onset of puberty is briefly discussed. (Endocrinology93: 1119, 1973)