TY - JOUR
T1 - Estrogen in the male
T2 - A historical perspective
AU - Hess, Rex A.
AU - Cooke, Paul S.
N1 - 1Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA and 2Department of Physiological Sciences, University of Florida, Gainesville, Florida, USA ∗Correspondence: Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, IL 61802, USA. E-mail: [email protected] †Grant Support. This work was supported in part by National Institutes of Health grants HD087528 and HD088006 (to P. S. Cooke)
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Estrogens have traditionally been considered female hormones. Nevertheless, the presence of estrogen in males has been known for over 90 years. Initial studies suggested that estrogen was deleterious to male reproduction because exogenous treatments induced developmental abnormalities. However, demonstrations of estrogen synthesis in the testis and high concentrations of 17β-estradiol in rete testis fluid suggested that the female hormone might have a function in normal male reproduction. Identification of estrogen receptors and development of biological radioisotope methods to assess estradiol binding revealed that the male reproductive tract expresses estrogen receptor extensively from the neonatal period to adulthood. This indicated a role for estrogens in normal development, especially in efferent ductules, whose epithelium is the first in the male reproductive tract to express estrogen receptor during development and a site of exceedingly high expression. In the 1990s, a paradigm shift occurred in our understanding of estrogen function in the male, ushered in by knockout mousemodels where estrogen production or expression of its receptors was not present. These knockout animals revealed that estrogen's main receptor (estrogen receptor 1 [ESR1]) is essential for male fertility and development of efferent ductules, epididymis, and prostate, and that loss of only the membrane fraction of ESR1 was sufficient to induce extensive male reproductive abnormalities and infertility. This review provides perspectives on the major discoveries and developments that led to our current knowledge of estrogen's importance in the male reproductive tract and shaped our evolving concept of estrogen's physiological role in the male.
AB - Estrogens have traditionally been considered female hormones. Nevertheless, the presence of estrogen in males has been known for over 90 years. Initial studies suggested that estrogen was deleterious to male reproduction because exogenous treatments induced developmental abnormalities. However, demonstrations of estrogen synthesis in the testis and high concentrations of 17β-estradiol in rete testis fluid suggested that the female hormone might have a function in normal male reproduction. Identification of estrogen receptors and development of biological radioisotope methods to assess estradiol binding revealed that the male reproductive tract expresses estrogen receptor extensively from the neonatal period to adulthood. This indicated a role for estrogens in normal development, especially in efferent ductules, whose epithelium is the first in the male reproductive tract to express estrogen receptor during development and a site of exceedingly high expression. In the 1990s, a paradigm shift occurred in our understanding of estrogen function in the male, ushered in by knockout mousemodels where estrogen production or expression of its receptors was not present. These knockout animals revealed that estrogen's main receptor (estrogen receptor 1 [ESR1]) is essential for male fertility and development of efferent ductules, epididymis, and prostate, and that loss of only the membrane fraction of ESR1 was sufficient to induce extensive male reproductive abnormalities and infertility. This review provides perspectives on the major discoveries and developments that led to our current knowledge of estrogen's importance in the male reproductive tract and shaped our evolving concept of estrogen's physiological role in the male.
KW - Efferent ductules
KW - Estrogen
KW - Male reproduction
KW - Prostate
KW - Rete testis
KW - Testis
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U2 - 10.1093/biolre/ioy043
DO - 10.1093/biolre/ioy043
M3 - Review article
C2 - 29438493
AN - SCOPUS:85054970149
SN - 0006-3363
VL - 99
SP - 27
EP - 44
JO - Biology of reproduction
JF - Biology of reproduction
IS - 1
ER -