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Estrogen Receptor Null Mice: What Have We Learned and Where Will They Lead Us?

Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709

I. Introduction—A Historical Perspective

II. Estrogen Receptors (ER)

A. Gene and mRNA structure

B. Mechanism of ER action

C. Generation of the estrogen receptor null mice

III. Reproductive Tract Phenotypes of the Female

A. Uterus

B. Vagina

C. Oviduct

D. Ovary

IV. Mammary Gland

A. ERKO phenotype

B. ßERKO phenotype

C. ER and oncogene-induced tumorigenesis: Wnt-1/ERKO mice

V. Reproductive Tract Phenotypes of the Male

A. Testicular function and spermatogenesis

B. Accessory sex organs

VI. Neuroendocrine System

A. Hypothalamic-pituitary axis

B. Behavior

VII. Phenotypes in Peripheral Tissues

A. Skeletal system

B. Cardiovascular system

C. Adipogenesis

VIII. Comparison with Human Disease and Models of Deficient Estrogen Action

A. Ovarian carcinogenesis

B. Chronic anovulation

C. ER and aromatase deficiency

IX. Summary