Aromatase activity and bone loss

Abstract

Aromatase is a specific component of the cytochrome P450 enzyme system that is responsible for the transformation of C19 androgen precursors into C18 estrogenic compounds. This enzyme is encoded by the CYP19A1 gene located at chromosome 15q21.2, that is expressed in ovary and testis not only but also in many extraglandular sites such as the placenta, brain, adipose tissue, and bone. The regulation of the level and activity of aromatase determines the levels of estrogens that have endocrine, paracrine, and autocrine effects on target issues including bone. Importantly, extraglandular aromatization of circulating androgen precursors is the major source of estrogen not only in men (since only 15% of circulating estradiol is released directly by the testis) but also in women after the menopause. Several lines of clinical and experimental evidence now clearly indicate that aromatase activity and estrogen production are necessary for longitudinal bone growth, attainment of peak bone mass, the pubertal growth spurt, epiphyseal closure, and normal bone remodeling in young individuals. Moreover, with aging, individual differences in aromatase activity and thus in estrogen levels may significantly affect bone loss and fracture risk in both genders.