Hudson Institute of Medical Research, Clayton, Vic 3168
Models of estrogen insufficiency have revealed new and unexpected roles for estrogens in both males and females. These models include natural mutations in the aromatase gene, as well as mouse KOs of aromatase and the estrogen receptors. Some of these roles apply equally to males and females and do not relate to reproduction, for example the bone, vascular and “Metabolic Syndrome” phenotypes. We have studied the phenotypes of several men with natural inactivating mutations in the aromatase gene as well as mice in which the gene has been disabled (ArKO mice). Some of the phenotypes of these mice are summarized below:
Infertility and lack of sexual behavior in both males and females.
Progressive defects in folliculogenesis and spermatogenesis.
Elevated gonadotropins and T levels.
Loss of bone mass in both females and males.
Metabolic syndrome with insulin resistance, truncal obesity, male-specific hepatic steatosis, and defective vascular endothelial and smooth muscle function.
Development of male-specific Obsessive Compulsive Disorder.
Many of these phenotypes are also present in aromatase – deficient humans, as will be presented.