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...

Genistein as an anti-inflammatory agent

“…Isoflavones selectively binds to the estrogen beta receptor [12], being efficiently blocked by ICI 182,780 [13]. Genistein was injected every second day and 795 nmoles of ICI 182,780 every fifth day.…”

Estrogen-mediated immunosuppression in autoimmune diseases

“…The role of estrogen in normal male mice, and 295 Vol. 47,1998 Estrogen-mediated immunosuppression Ⅵ the cause of the infertility in ERKO males, has recently been shown to be the transport and storage of sperm in the epididymis [164]. The expression of ER regulating the immune system is probably similar in females and males since estrogen treatment suppressed CIA in both sexes [96].…”

“…In CIA, a pure estrogen inhibitor, ICI 182.870 [176] blocks the immune suppression mediated by endogenously produced estrogens in lower doses than it affects the estrous cycling tested by examining vaginal smears (L. Jansson, manuscript in preparation). ICI 182.870 binds to both ERa and ERb [164] and it is therefore not possible from these data to determine whether estrogen-induced suppression of CIA is mediated by one single ER only or by both.…”

The effects of environmental hormones on reproduction

“…It also causes sloughing of germ cells, seminiferous tubule atrophy, occlusion of the efferent ducts and other abnormalities of the male reproductive system [53]. Since the efferent ducts contain oestrogen receptors [54][55][56] and fluid resorption by the ducts appears to be under oestrogenic control [57], it is possible that the effects of benomyl, at least on these structures, is oestrogenic or anti-oestrogenic. PCBs are manufactured through the progressive chlorination of biphenyl, theoretically, giving rise to 209 congeners [4,11].…”

“…During the critical period of sexual differentiation, one might anticipate that exposure of a chromosomal male to antiandrogenic xenobiotics would interfere with the androgen-dependent differentiation of the Wolffianderived structures and/or with the normal development of the male genitalia. Since oestrogen receptors are present in the male reproductive tract [54,55,57,135,[137][138][139][140], xenooestrogens could also interfere with the proper development of these structures. Likewise, xenoandrogens could masculinize the developing female foetuses, since the structures of their reproductive tracts contain androgen receptors [141].…”