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)

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Summary

ESTROGENS AND MALE REPRODUCTION

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

INTRODUCTION
PHYSIOLOGY Estrogen Biosynthesis in Males
Non Genomic Estrogen
Distribution of ERs and aromatase in fetal rodents
Distribution of ERs and aromatase in adult rodent reproductive tract
Efferent ductules
Distribution of ERs and aromatase in the human male reproductive system
ROLE OF ESTROGENS IN MALE REPRODUCTION
Testicular histology
Depletion or germ cell arrest at primary spematocyte level
Estrogens and Prostate
Estrogens and Male Sexual Behavior
Estrogens and Gender Identity and Sexual Orientation
Sexual function
Estrogens and Sexual Behavior
Estrogens and Metabolism
Estrogens and Bone
Effects of Exposure to Excess Estrogens in Animals
Effects of Exposure to Excess estrogens in Humans
CLINICAL IMPLICATIONS OF ESTROGENS IN MALES
Effects on semen analysis
Aromatase inhibitors
Findings
CONCLUSIONS
Full Text
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