Estrogen, bone, growth and sex: A sea change in conventional wisdom

The discovery of a man with a homozygous mutation in the estrogen receptor ct gene, which results in estrogen-receptor a resistance, and of males and females with autosomal recessive mutations in the CYP19 gene encoding aroma tase, which leads to a failure to synthesize estrogens, has challenged conv entional wisdom about the 'unimportant' role of estrogen in the male, For e xample, in the male, estrogen (not androgen) derived from direct testicular secretion (similar to 20%) and from extragonadal aromatization of testoste rone and androstenedione (similar to 80%), is the critical sex hormone in t he pubertal growth spurt, skeletal maturation, accrual of peak bone mass, a nd the maintenance of bone mass in the adult. Estrogen stimulates chondroge nesis in the epiphyseal growth plate increasing pubertal linear growth, At puberty, estrogen promotes skeletal maturation and the gradual, progressive closure of the epiphyseal growth plate, possibly as a consequence of both estrogen-induced vascular and osteoblastic invasion and the termination of chondrogenesis, In addition, during puberty and into the third decade, estr ogen has an anabolic effect on the osteoblast and an apoptotic effect on th e osteoclast, increasing bone mineral acquisition in axial and appendicular bone. In the adult, estrogen is important in maintaining the constancy of bone mass through its effects on remodeling and bone turnover. Establishing a role for estrogen does not exclude a direct action of testosterone on bo ne in the human male (especially on cortical bone), but this action is less characterized than thought in the past and is relatively minor in comparis on with the major effect of estrogen in the male.