PEDIATRIC ENDOCRINOLOGY UPDATE - AN OVERVIEW - THE ESSENTIAL ROLES OFESTROGENS IN PUBERTAL GROWTH, EPIPHYSEAL FUSION AND BONE TURNOVER - LESSONS FROM MUTATIONS IN THE GENES FOR AROMATASE AND THE ESTROGEN-RECEPTOR

The goals of this presentation are to review the essential roles of ar omatase, estrogens and the estrogen receptor in pubertal growth. Estro gen deficiency due to mutations in the aromatase gene (CYP19) and estr ogen resistance due to disruptive mutations in the estrogen receptor g ene have no effect on normal male sexual maturation in puberty. Howeve r, they lead to absence of the pubertal growth spurt, delayed bone mat uration, unfused epiphyses, continued growth into adulthood and very t all adult stature in both sexes. Gonadotropin and androgen levels are elevated in patients with either estrogen deficiency (aromatase defici ency) or estrogen resistance (estrogen receptor mutation). Glucose int olerance, hyperinsulinemia and lipid abnormalities are also present. S keletal integrity is compromised. Increased bone turnover, reduced bon e mineral density and osteoporosis develop in both sexes. Sexual orien tation is appropriate in males and females. In females, aromatase defi ciency in the ovary causes pubertal virilization and multicystic ovari es because of elevated gonadotropins and androgens. Simultaneously, se condary sexual maturation fails to occur. Placental aromatase deficien cy results in virilization of the mother and her female fetus because of the accumulation of potent androgens which are not converted to est rogens. The male fetus has normal genitalia. In conclusion, estrogens are essential for normal female secondary sexual maturation, bone matu ration, epiphyseal fusion, pubertal growth spurt and achievement of no rmal bone mineral mass. Estrogens also influence insulin sensitivity a nd lipid homeostasis. However, estrogens do not appear to be essential for fetal survival, placental growth, or female sexual differentiatio n.