The first estrogen receptor was discovered in the late 1950s, a period that Jan-Ǻke Gustafsson refers to as BC (before cloning). Forty years later, he and colleagues were looking for a completely unrelated androgen receptor in the prostate when they stumbled across a nuclear hormone receptor with near-perfect homology to the estrogen receptor's DNA binding region, and 58% homology at the c-terminal domain. "We thought it might be a cloning variant," Gustafsson says, but as soon as they realized it was a novel estrogen receptor, they raced to publish the results.
Dubbing the original protein ERα and this version ERβ, the group and others found the protein expressed in dozens of tissues, but surprisingly, and fortuitously for some clinical applications, not in endometrial tissue or the pituitary. The original in situ hybridizations from rat prostate and ovarian tissue are shown along with a page from Gustafsson's lab notebook describing the ...