Human models of aromatase deficiency.

Estrogens exert a wide range of biological effects in both sexes also on non-reproductive systems andorgans. Human congenital estrogen deficiency, due to an inactivating mutation of the aromatase gene,leads to the lack of the estrogen synthesis, with gonadotropins and circulating testosterone ranging fromnormal to elevated. The aromatese-deficient females show hyperandrogenism and virilization at birthwith ambiguous genitalia. During childhood there are a dysfunction in the LHRH-LH/FSH axis and a progressivedelay in bone age. At puberty they showprimary amenorrhea, no breast development,worseningof the virilization and the absence of growth spurt. The clinical phenotype in the male affected subjectscomprises tall stature, persistent linear growth and delayed bone age, osteopenia/osteoporosis, eunuchoidbody proportion, different degrees of glucose–insulin and of fertility impairment. These phenotypes suggestthe physiological role of estrogens on the skeleton, on pituitary function, on the reproductive system,on glucose metabolism, being the precise mechanism on each of these functions not yet known in detail.The estradiol replacement treatment leads to a complete epiphyseal closure and to the skeletal maturation.Moreover, the increasing knowledge on the role of estrogen in several metabolic pathways could beimportant for a better management of several metabolic diseases.