Estrogen receptor mutations

The purpose of this paper is to review potential novel functional pathways by which estradiol and estrogenic compounds elicit biological responses in mammals. We will limit our approach to those novel functions suggested by p henotypes associated with estrogen receptor-alpha (ER alpha) gene mutations and polymorphisms. The study of these pathways has been greatly aided by t he availability of ER alpha-minus mice, which lack classic biological respo nses to estradiol. In addition, the availability of an ER alpha-minus human family, aromatase-minus human families, and in the near future an aromatas e-minus mouse model will allow correlations of novel phenotypes with the la ck of active ER alpha protein. The ER alpha-minus mice can potentially be u sed to characterize in depth novel clinical phenotypes that link the functi ons of estrogens with sexual maturation, cardiovascular disease, osteoporos is, diabetes, and cancer. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.