CLINICAL SIGNIFICANCE

Estrogens

Estrogens and estrogen-like molecuels exert their effects through binding to and activating estrogen receptors. Estrogens are clinically important in both men and women. Estrogen affects growth, differentiation, and the development of reproductive tissues, including uterus, vagina, and mammary glands in women and testis, epididymus, and prostate in men. In bone tissue, estrogen maintains bone density and helping prevent osteoporosis; in the cadiovascular system estrogen exerts anti-atherosclerotic effects by lowering circulating cholesterol, and within the central nervous system estrogen influences reproductive behavior, general mood, and is implicated in slowing the processes that lead to dementia. The neuroprotective efficacy of estrogens observed in neuronal culture models and in animal models include the attenuation of neuronal death in cerebral ischemia, in traumatic injury, and in Parkinson's disease. Most commonly, estrogens are used as hormone therapy in treating and preventing postmenopusal symptoms and as contraceptive agents. Anti-estrogens are used in treatment of certain breast cancers and some prostate cancers. For a more complete overview on estrogen, its effects, and therapeutic uses, see National Cancer Institute's Behind the News' web site Understanding Estrogens

Environmental Estrogens

• Phytoestrogen- natural compounds derived from plants
• Xenoestrogens- synthetic compounds released into the envoronment

Environmental estrogens bind to ER with varying affinities and mimic the actions of hormonal estrogen. While environmental estrogens are often considered non-beneficial, phytoestrogens are often associated with health benefits. They include two main classes, isoflavenes and lignans. Soy protein containing foods are a rich source of isoflavene phytoestrogens, such as genistein and daidzein while whole grains and flax seeds are sources of lignans. These compounds are reported to have beneficial effects on lowering coronary heart disease and some cancers.

Targets

• Reproductive System
  • Breast and Ovaries (NCBI-OMIM)
  • Uterus
  • Endometrial Lining
  • Testis/Epididymis
  • Prostate
• Bone Tissue(NCBI-OMIM)
• Cardiovascular System
• Central Nervous System
• Gastrointestinal Tract
• Lipid Metabolism
• Adipose Tissue

Click here for more information on this target tissue as it relates to health

Selective Estrogen Receptor Modulators (SERM)

Other natural compounds and synthetic drugs are also capable of binding to the estrogen receptor. Selective estrogen receptor modulators constitute a group of compounds capable of regulating ER-mediated gene expression in different tissues. Some mimic the effects of estrogen, others have antiestrogenic effects, and some may even have dual roles, depending on the organ system and physiological context. SERMs are divided into three major categories:

Triphenylethylenes:

• Tamoxifen (Nolvadex; AstraZeneca Pharmaceuticals, Wilmington, DE)
• Toremifene (Fareston;Schering Corp, Kenilworth, NJ)

Other nonsteroidal compounds:

• Raloxifene (Evista; Eli Lilly and Co, Indianapolis, IN)
• LY353381 and LY357489 (Evista; Eli Lilly and Co, Indianapolis, IN)

Steroidal compounds:

• ICI182,780 (Faslodex; AtraZeneca Pharmaceuticals)

Reference: Osborne CK, Zhao H, Fuqua SA. Selective estrogen receptor modulators: structure, function, and clinical use. J Clin Oncol. 2000 Sep;18(17):3172-86.

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