Estrogen in the male: a historical perspective†

Abstract

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 mouse models 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.

Motile cilia of the male reproductive system require miR-34/miR-449 for development and function to generate luminal turbulence

“…Therefore, the mechanisms involved in the early onset of this lesion warrants further investigation. The accumulation of luminal fluid in the proximal region, as well as in the rete testis and seminiferous tubules, is similar to that reported for Esr1 knockout and antiestrogen-treated mice, in which the primary lesion is the inhibition of nonciliated cell physiology of ion transport/exchange and water reabsorption (38,39). Disruption of ESR1 activity does not produce ED obstruction, as spermatozoa in these animal models are found in the cauda epididymis (40); however, the ED luminal fluid cannot be reabsorbed and, thus, exceeds the transport capacity of the more narrow distal ED.…”

Differential gene expression profiles of human efferent ducts and proximal epididymis

“…Considering the abundance of ciliated cells bordering the intraluminal luminal compartment, similar functions may be attributed to efferent ducts in humans. The estrogen receptor and its involvement in trans‐epithelial water reabsorption is a major feature of the efferent duct . This process is essential to increase the concentration of testicular spermatozoa entering the epididymis.…”

“…Efferent ducts are described as linear tubules connecting the single epididymal tubule to the testicular rete testis . They are found in different numbers depending on the species .…”

Co-expression of the aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) in the developing teeth of rat offspring after rat mothers’ exposure to 2,3,7,8-tetrachlorodib

“…29,36,37 Therefore, in the absence of estrogens, an increased expression of ER within the cytoplasm in TCDD-treated animals may be explained by a permanent activation of ER synthesis by TCDD degradation end products or inhibition of its transfer to the nucleus. 36,37 We have also found that the increased expression of ER was noted in the TCDD group, whereas the expression of AhR decreased. An increased level of ER, as an alternative pathway in the anti-inflammatory process, may be a part of the cellular self-defense against TCDD biotransformation products.…”