A role for oestrogens in the male reproductive system

Abstract

Oestrogen is considered to be the 'female' hormone, whereas testosterone is considered the 'male' hormone. However, both hormones are present in both sexes. Thus sexual distinctions are not qualitative differences, but rather result from quantitative divergence in hormone concentrations and differential expressions of steroid hormone receptors. In males, oestrogen is present in low concentrations in blood, but can be extraordinarily high in semen, and as high as 250 pg ml −1 in rete testis fluids 1,2 , which is higher than serum oestradiol in the female 3 . It is well known that male reproductive tissues express oestrogen receptors [4][5][6][7] , but the role of oestrogen in male reproduction has remained unclear. Here we provide evidence of a physiological role for oestrogen in male reproductive organs. We show that oestrogen regulates the reabsorption of luminal fluid in the head of the epididymis. Disruption of this essential function causes sperm to enter the epididymis diluted, rather than concentrated, resulting in infertility. This finding raises further concern over the potential direct effects of environmental oestrogens on male reproduction and reported declines in human sperm counts 8,9 .Classic cellular responses to the hormone oestrogen are mediated through nuclear oestrogen receptors (ER), which function as ligand-dependent transcription factors. Efferent ductules of the testis are known to express high amounts of ER-α 10,11 , higher even than uterine tissue, and both the α and β forms of ER are present in efferent ductules and the epididymis 10 . These ductules form a series of small tubules that transport sperm from the testis to the epididymis 12 . In humans, one third of the epididymal head consists of efferent ductules 13 . In addition to ciliated cells that stir the luminal fluid, their epithelia contain nonciliated cells that resemble proximal tubule cells in the kidney. The non-ciliated cells have a reabsorptive function that results in the uptake of water, ions and proteins from the ductal lumen 12,14 . Ductules in the rat reabsorb nearly 90% of the rete testis fluid, coupling water and active ion transport in an electroneutral environment, in which Na + and water are reabsorbed at equal rates, thereby increasing the concentration of sperm as they enter the Correspondence and requests for materials should be addressed to R.A.H. (r-hess@uiuc.edu). 15,16 . This method of concentrating sperm improves their survival and maturation during epididymal storage and ensures that a large number of sperm are released upon ejaculation, increasing the randomness of fertilization and providing genetic variation 14 . These data and the observation that efferent ductules contain the highest concentrations of ER in the male led us to hypothesize that oestrogen participates in the regulation of fluid reabsorption in the male reproductive tract. HHS Public AccessTo test this hypothesis, we used the ER-α gene knockout mouse (ERKO) 17,18 . The ERKO male is infertile 18 , but its testes appear normal un...

The faah gene is the first direct target of estrogen in the testis: role of histone demethylase LSD1

“…Many studies have underlined the importance of estrogens in male fertility [5,[32][33][34], as demonstrated by the expression of ERs and aromatase in the testis and by the fact that mice lacking either ERa [5] or aromatase [6] show altered spermatogenesis and infertility. However, evidence for a direct action of E 2 on the seminiferous epithelium is still missing, and remarkably genes that are regulated by E 2 through classical ERE sequences remain unknown in the testis.…”

Effect of 17‐α‐ethynylestradiol on germ cell proliferation in organ and primary culture of medaka (Oryzias latipes) testis

“…However, it has become quite clear now that E2 is an essential hormone in male reproduction (Hess et al 1997(Hess et al , 2001Sharpe 1998). The presence of both ␣ and ␤ estrogen receptors was reported in several cell types of the testis, including both somatic and germ cells (e.g.…”

Estrogen receptor β acts as a dominant regulator of estrogen signaling

“…Lately the role of estrogens in heart and vascular protection and for maintenance of bone mass has also attracted considerable interest (Farhat et al, 1996). Studies of ERa knock-out mice have revealed important functions for estrogens also in the male reproductive system (Hess et al, 1997;Lubahn et al, 1993). Adversely, estrogens have been implicated in development and progression of tumors in breast and endometrium (Ciocca and Fanelli, 1997).…”