Abstract
The role of estrogen on male reproductive function has become clearer in the last decade. During these years the study of the effect of testosterone, estrogen or an aromatase inhibitor in hypogonadal men provided a first evidence of the effects of estrogens in the regulation of gonadotropin secretion. At the same time, the development of a line of transgenic male mice lacking estrogen receptor α, estrogen receptor β or aromatase gene provided further evidence about the role of estrogens not only in the regulation of gonadotropin secretion, but also on the effects of estrogens on testicular function and development. A confirmation of these actions of estrogens came from the observation of naturally occurring mutations of the estrogen receptor and of the aromatase gene in human males. Based on these data it has been demonstrated that estrogens are major regulators of gonadotropin secretion acting both at pituitary and hypotalamic level. The presence in the human reproductive structures of estrogen receptor α, estrogen receptor β and the aromatase enzyme indicates the existence of receptor α, estrogen receptor β or aromatase estrogen actions at this level. Anyway, the precise role of estrogens in testicular development and function and on the regulation of human spermatogenesis has not yet been precisely clarified.
Highlights
From an historical perspective, estrogens were identified about 85 years ago and estradiol was identified in 1940, reviewed in (1)
The term estrogen refers to any substance, natural or synthetic, able to interact with the estrogen receptor (ER) (27,28). 17β-estradiol is the prevalent endogenous estrogen form in mammals, many of its metabolites could be detected with several degrees of estrogenic activity (29)
Aromatase enzyme and ERs are widely expressed in the male reproductive tract both in animals and humans (45,46), implying that estrogen biosynthesis occurs at this site and that both locally produced and circulating estrogens may interact with ERs in an intracrine/paracrine and/or endocrine fashion (29)
Summary
Vincenzo Rochira, MD, PhD,[1,2] Bruno Madeo, MD, PhD,[2] Chiara Diazzi, MD, PhD,[2] Lucia Zirilli, MD, PhD,[2] Daniele Santi,[1,2] and Cesare Carani, MD1
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