The recent cloning by Thornton (2001) of estrogen, progesterone and corticoid receptors from lamprey provides important insights into the early evolution of adrenal and sex steroid receptors and an opportunity to elucidate the ancient steroids that regulated gene transcription. Inclusion of lamprey sequences in a steroid receptor phylogeny indicates that the estrogen receptor is the most ancient of these receptors, followed by the progesterone receptor and the corticoid receptor. Thornton proposed that estradiol was the earliest of the steroids to activate a steroid receptor. An alternative hypothesis is that a steroid in the Delta(5) pathway activated the ancestral estrogen receptor.

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