The role of estrogens in male skeletal development.
The developing human skeleton is known to be influenced by the presence of sex steroids. In girls, estrogens have been considered to be the dominant hormone, whereas in boys, androgens have occupied a primary physiological role in terms of bone mass accrual. Although these views are still current, recent observations made of rare defects in estrogen receptor sensitivity or estrogen synthesis have called attention to the importance of estrogens in the developing male skeleton. In these human genetic models, the affected men have demonstrated continuous linear skeletal growth, open epiphyses, lack of pubertal growth spurt, and reduced bone mass. In the example of men with aromatase deficiency, lacking estrogens from birth, administration of estrogen led to impressive increases in bone density, maturation of the skeletal growth plates, and cessation of linear growth. Animal models mimicking these human syndromes by knockout technology, have tended to support these observations. The data argue for a primary role of estrogens in the developing male skeleton, while not diminishing the important role for androgens.