The discovery of a second estrogen receptor has redefined the estrogen signaling pathway and may have broad implications on estrogen-responsive tissues.1 The new estrogen receptor, named estrogen receptor-beta (ERbeta), is preferentially expressed in the prostate and maintains some characteristics that are different from ERalpha.2 The rat tissue distribution and/or the relative level of ERalpha and ERbeta expression seems to be quite different, i.e., moderate to high expression in uterus, testis, pituitary, ovary, kidney, epididymis, and adrenal for ERalpha and prostate, ovary, lung, bladder, brain, bone, uterus, and testis for ERbeta. Within the same organ it often appears that the ER subtypes are expressed in different cell types, supporting the hypothesis that the ER's may have different biological functions. The discovery of ERbeta suggests the existence of two previously unrecognized pathways of estrogen signaling, via the ERbeta subtype in tissues exclusively expressing this subtype and via the formation of heterodimers in tissues expressing both ER subtypes.The existence of two ER subtypes, their differential expression pattern, and different actions on certain response elements could provide explanations for the striking species-, cell-, and promoter-specific actions of estrogens and antiestrogens.3 Both estrogen receptors appear to be involved in a multitude of regulatory events.
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