Aromatase in human physiology and pathology: implications of human aromatase deficiency

cP450arom is essential in the biosynthesis of estrogens from androgen precursor. Aromatase expression and activity influence the androgen–estrogen balance in target tissues. Aromatase expression in the placenta protects the fetus and the mother from virilizing effects of fetal adrenal androgens. In affected patients in particular adult males show increased body weight, glucose intolerance, insulin resistance, and hyperlipidemia. Currently, the mechanism is poorly understood. Estrogen therapy improves glucose homeostasis and lipid metabolism but normal values are not achieved. A minimal amount of estrogens is required for the negative feedback mechanism of FSH secretion in females during infancy, childhood, and puberty. Conversely, estrogens are not involved in the regulation of FSH secretion in infant boys, but it appeared to be one of the components of gonadal feedback on LH and FSH in adult men. Different adult testis sizes and sperm abnormalities were reported. The role of estrogens in normal fetal ovary development, if any, is poorly understood. In the ArKO mice model and in nearly all 46,XX aromatase-deficient (AD) patients, normal fetal ovary development was described. Therefore estrogens might not be involved in fetal ovary development, even though a few cases with postnatally atrophic ovaries have been reported suggesting that after birth estrogens are required to prevent ovarian atrophy. Polycystic ovaries are very frequently observed in AD females mainly in puberty secondary to constantly high-serum FSH levels. Estrogens are involved in the pubertal growth spurt, skeletal maturation, and bone mineral density and it improves with estrogen therapy in both sexes, however scarce information is available on the role of estrogen in bone mineral acquisition during childhood. Finally, patients with cP450arom deficiency represent another “experiment of nature” that has proven to be a fertile source of knowledge on estrogen physiology and pathology.