Aromatase activity and bone homeostasis in men.

[aromatase deficiency]

It is known that sex steroid hormones play an important role in the maintenance of bone mass in males as well as in females . Even though androgens are the major sex steroids in men , their primacy in regulating male skeletal remodeling has been increasingly questioned as direct and indirect evidence emerged suggesting that estrogens may also play a major role in male skeletal health . Recent data suggested that a threshold level of bioavailable estradiol is needed to prevent bone loss , and that with aging an increasing percentage of elderly men begin to fall below this level . The testes account for , at most , 15 % of circulating estrogens in the male ; the remaining 85 % comes from peripheral aromatization of androgen precursors in different tissues , including bone . Human models of aromatase deficiency were the first to demonstrate the critical importance of the conversion of circulating androgens into estrogen in regulating male skeletal homeostasis . All four cases of aromatase-deficient men reported to date showed an identical skeletal phenotype , characterized by tall stature due to continued longitudinal growth , unfused epiphyses , high bone turnover , and osteopenia . Studies using knockout mice along with experimental observations in rats treated with an aromatase inhibitor provided useful information about the importance of aromatase in the male skeleton . Confirmatory evidence comes from recent interventional studies in adult men using aromatase inhibition , which confirmed that estrogens are critically important to the male skeleton by helping to control rates of bone remodeling . Intriguingly , common polymorphisms at the human aromatase (CYP 19 ) gene have been associated with differences in aromatase activity , bone turnover , and rates of bone loss in elderly men , suggesting that variations in aromatase efficiency may also be relevant for skeletal homeostasis . Several additional mechanisms have been proposed in which aromatase activity could be modulated under certain circumstances in different tissues . Additional studies are needed to identify how these genetic , environmental , pathological , and pharmacological influences might modulate aromatase activity in vivo , increasing or reducing estrogen production in males and thereby affecting skeletal health .

Diseases
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Diseases presenting "skeletal health" symptom

aromatase deficiency

phenylketonuria

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