Endocrine Abstracts

The discovery of naturally occurring, inactivating mutations of the aromatase gene and of the estrogen receptor (ER) gene in humans shed new light on the precise role of estrogen in several metabolic processes, both in male and female.

To date, few clinical cases of males with well-documented congenital aromatase deficiency (11 females and 8 males) have been reported in medical literature. All mutations accounting for aromatase deficiency have been located in regions encoding essential functions in the aromatization process. Aromatase-deficient males show persistent linear growth with delayed skeletal maturation and epiphyseal closure, eunuchoid body proportions, osteoporosis, various degrees of fertility impairment and strong evidences of metabolic syndrome (impaired lipid, glucose and liver metabolism). Moreover preliminary data demonstrate an impaired GH response to GHRH plus Arginine and serum IGF-I levels at the lower end of the normal range in four patients with aromatase deficiency.

The estrogen treatment in some of these patients demonstrated the crucial role of estrogens also in men. Particularly, estradiol treatment induces the pubertal growth spurt, the achievement and maintenance of normal skeletal proportions and of peak bone mass, and the inhibition of bone resorption. Moreover, among gonadotropin feedback it was shown that estrogens are the most effective gonadotropin-secretion inhibitor at pituitary level, particularly with respect to FSH, and that they act also at hypothalamic level. Nevertheless estrogens are not able to improve the fertility and to restore GH-IGF-1 axis function. After all, the human model of aromatase deficiency shows that estradiol treatment could act on heart and cardiovascular system by possible cardio-protective effects and prevention of atherogenesis, and on dysmetabolic pattern by an improvement of lipid profile, insulin sensitivity, and of liver homeostasis.

By studying the naturally occurring aromatase-deficient patients we are expanding our understanding of the essential role of estrogens in human physiology.