A single injection of estradiol to immature male chickens results in a very rapid increase in the number of both soluble and tightly bound nuclear estrogen binding sites. After an intermediate levelling off, a second longer lasting increase in binding sites is observed. Whereas the first rapid increase seems to be independent of RNA and protein synthesis, the second one obviously requires intact RNA and protein synthesis. From these results we conclude that there is a pool of cytoplasmic estrogen binding sites, which supplies the precursor for the nuclear binding sites. After this pool is exhausted, it is replenished by new synthesis of binding sites. However, although several laboratories have attempted to demonstrate directly the existence of such a cytoplasmic estrogen receptor in the chicken liver, all have so far been unsuccessful.
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