The biological significance of the interaction of estrogen agonists and antagonists with the estrogen receptor.
The identification and isolation of a soluble estrogen receptor protein from estrogen target tissues, e.g., uterus, more than 25 years ago provided a unique opportunity for the biochemical pharmacologist to study the interaction of agonist and antagonist molecules in a well-defined organ. Nonsteroidal antiestrogens have proved to be valuable research tools to study cell replication or estrogen specific protein synthesis, e.g., prolactin synthesis or progesterone receptor induction. During the past two decades the antiestrogen tamoxifen has become the endocrine treatment of choice for all stages of breast cancer. This fact has provided an additional incentive to study breast cancer cell replication. In the laboratory breast cancer cells can be used to study the direct actions of antiestrogens without the complicating aspects of pharmacokinetics and metabolism. Studies of the structure-activity relationships of antiestrogens compliment the current investigation of steroid hormone receptors as part of a superfamily of transcription factors. Antiestrogens will, in the future, provide valuable information (from X-ray crystallography) about the three-dimensional folding required if a steroid receptor complex is to prevent cell replication. Clearly this information, and the description of additional transcription factors in hormone-independent cells may prove to be critical for the development of new therapeutic opportunities.
Murphy
C S
CS
Department of Human Oncology, University of Wisconsin-Madison 53792.
Jordan
V C
VC
D000818:Animals; D004965:Estrogen Antagonists / Q000737:chemistry / Q000494:pharmacology*; D004967:Estrogens / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007536:Isomerism; D015394:Molecular Structure; D011960:Receptors, Estrogen / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013347:Subcellular Fractions / Q000187:drug effects
D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen