The development of estrogen receptor systems in the rat brain and pituitary: Postnatal development

Abstract

The postnatal development of the estrogen receptor system of the rat brain is described by means of data from in vitro cytosol binding assays and from in vivo cell nuclear experiments using 3H-labeled estrogens. Cytosol and nuclear measures give a similar picture of the changes in estrogen receptor levels from day 2–3 up to day 25 of postnatal life. Pituitary receptor levels reach a peak at day 10 and then decline slightly. A similar, though less pronounced, peak was seen in hypothalamus between days 8 and 15. In the amygdala, the concentration of receptors remains relatively constant apart from a slight increase around day 10. In the preoptic area, receptor levels increase throughout the entire period studied. In the cortex receptor levels increase between days 3 and 10 and then decline precipitously and remain low from day 15 onwards. In the midbrain and brain stem receptor levels remain low throughout the entire period. Occupation of estrogen receptors by estradiol in cell nuclei was investigated by means of an exchange assay. No occupation was seen in either cortex or limbic structures (hypothalamus, amygdala, preoptic area) of female pups on postnatal days 2–3; low level occupancy amounting to around 5% of capacity was seen in limbic structures but not in cortex of females on postnatal days 10–11 and 25–26. The possibility is discussed that this estrogen arises from testosterone via aromatization. The apparent absence of receptor occupation by endogenous circulating estradiol is discussed in relation to the presence and progressive disappearance of alpha-fetoprotein in the neonatal period. Data is presented showing that injected estrogens have a longer half-life in newborn rats than in 3-week-old animals and that estrogens such as diethylstilbestrol and moxestrol, which do not bind strongly to alpha-fetoprotein, gain access to brain estrogen receptors at lower doses compared to estradiol-17β.