The development of estrogen receptors and of the vitellogenic response to estradiol in embryonic chick liver

In liver of oviparous vertebrates, estradiol induces the synthesis of vitellogenin, the complex precursor of the egg yolk proteins. The development of the ability of the growing chick embryo to respond to exogenous estradiol by vitellogenin synthesis was determined by quantitation of labeled vitellogenin synthesized in vitro by livers from estrogen-treated embryos at different developmental stages. Vitellogenin was identified by electrophoresis of the specific immunoprecipitates. Although traces of vitellogenin synthesis are detectable in estrogen-treated 13- day embryos, the response is not firmly established until day 15. It has been known for some time that chick liver contains a salt-soluble nuclear estrogen receptor, the concentration of which is considerably enhanced by estrogen treatment in vivo. Specific high-affinity binding of estradiol in cytosol has only recently been reproducibly detected. The cytoplasmic binder is very labile, and precautions against proteolysis as well as separation from a high concentration of a low-affinity estrogen-binding protein are essential for consistent demonstration of the cytoplasmic high-affinity binding activity. The specificity and affinity of the binder and its depletion on estrogen treatment make it likely that it is a receptor. The ontogeny of the cytoplasmic receptor and of the response of the soluble nuclear receptor to exogenous estradiol has been investigated in White Leghorn chick embryos. The 10-day embryonic liver contains very little cytoplasmic receptor, and the concentration of nuclear receptor is only marginally stimulated by deposition of a large dose of estradiol into the egg yolk. At day 12, however, the cytoplasmic receptor concentration has risen to equal that of the hatched chick, and estrogen treatment results in a substantial increase in the soluble nuclear receptor. Even though the nuclear receptor response at day 12 is the same as at day 15, vitellogenin synthesis is found only at the later stage. The cytoplasmic receptor concentration in untreated embryos after day 12 undergoes a gradual increase up to 3-fold at day 19, and then declines to the 12-day level and remains constant for several weeks after hatching. The physiological significance of the apparent peak of cytoplasmic receptor at day 19 is not understood.