Two Binding Sites for Estradiol in Rat Uterine Nuclei: Relationship to Uterotropic Response*

Abstract

Estradiol administration causes an increase in two specific binding components in uterine nuclei of mature ovariectomized rats. One of these sites (type I) represents the estrogen receptor which binds estradiol with high affinity (dissociation constant, 1 nM) and low capacity (1 pmol/uterus) and is translocated from the cytoplasm to the nucleus. The second component (type II) binds estradiol with a higher capacity than type I sites and displays a saturation curve which is sigmoidal. Hence, no accurate estimation of the dissociation constant can be made. The differential stimulation of type II sites by estradiol and estriol suggests that this is a specific estrogenic response and is highly correlated with uterine growth. A single injection of estradiol results in long term retention of type I sites (>6 h), rapid and sustained elevations of type II sites (1-72 h), and true uterine growth. In contrast, estriol injection caused a rapid increase in type I sites which was not accompanied by an increase in type II sites, and no true uterine growth occurred. Conversely, the administration of estriol by paraffin implant sustained elevated nuclear levels of type I sites, increased nuclear type II sites 2- to 3-fold above controls, and stimulated true uterine growth 48 h after hormone administration. Similar results were obtained with an estradiol implant. These data suggest that estrogen stimulation of true uterine growth may require long term (6-24 h) nuclear retention of type I sites and sustained elevation in type II sites. These elevations in nuclear type II sites persist (1-72 h) long after the disappearance of type I sites (24 h) from the nucleus. We conclude that elevated levels of type II sites correlate well with the biosynthetic events associated with the long term uterotropic response to estrogenic hormones. These sites may constitute a component of the genome which regulates estrogen-stimulated uterine growth.