The Role of Estrogen in Pubertal Skeletal Physiology: Epiphyseal Maturation and Mineralization of the Skeleton

The year 1994 is likely to be remembered by many endocrinologists as the year in which dramatic new light was shed on the role played by estrogen in human skeletal physiology. It was in 1994 that two new syndromes were described, each representing a human model in which estrogen action was lacking. The first case was a female with an aromatase defect and a resultant inability to synthesize estrogen, and the second case was a man with an estrogen receptor gene defect that resulted in a non-functioning estrogen receptor and complete estrogen resistance. By examining the phenotypes of these two individuals, we were able, for the first time, to see what pubertal skeletal changes occur in the absence of estrogen action and directly extrapolate the role of estrogen in skeletal physiology. What has become abundantly clear is that it is estrogen and not androgen that is responsible for pubertal epiphyseal maturation and skeletal mineralization.