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“ Shall it be male or female? say the cells, And drop the plum like fire from the flesh .” —Dylan Thomas The presence of steroid hormone receptors in the vasculature of male animals has been recognized for more than two decades,1,2 and the ability of vascular estrogen receptors (ERs) to activate gene expression in vascular smooth muscle and endothelial cells from both sexes is now well established.3 We know now that normal ER function is required for skeletal development in the human male,4 male fertility,5 and normal cardiovascular development and function in males as well as females.6–8 In men, circulating estrogen levels are quite low and substantially lower than androgen levels.How do cardiovascular tissues in men become exposed to estrogen? Males generate estrogen by synthesizing it directly from testosterone in target tissues. The enzyme aromatase, a member of the P450 superfamily of enzymes, is responsible for the conversion of C19 androgenic steroids to the corresponding estrogens, a reaction known as aromatization, since it involves conversion of the A-ring of androgens to the corresponding phenolic A-ring characteristic of estrogens (Figure). Aromatase is widely expressed in ovary, placenta, hypothalamus, liver, muscle, adipose tissue, and of note, in vascular smooth muscle and endothelial cells.9–12 Estradiol is therefore generated directly in the male vasculature, where it can activate ERs in both the cells in which it arises and in neighboring vascular smooth muscle and endothelial cells. The enzyme aromatase, a member of the P450 superfamily of enzymes, is responsible for the conversion of C19 androgenic steroids to the corresponding estrogens, a reaction known as aromatization. Two new studies discussed here support the hypothesis that aromatization of testosterone to estrogen is required for the maintenance of normal endothelial function and vascular tone in males.13,14Two new …

Hormonal Regulation of Normal Vascular Tone in Males