Immunolocalisation of oestrogen receptor-α within the testis and excurrent ducts of the rat and marmoset monkey from perinatal life to adulthood

Fisher, Jane S.; Millar, Michael; Majdič, Gregor; Saunders, Philippa T. K.; Fraser, Hamish M.; Sharpe, R. M.

doi:10.1677/joe.0.1530485

Cited by 250 publications

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“…Therefore, it is also possible that changes of the efferent ductule epithelium in the adult ␣ERKO males are, at least in part, due to the developmental abnormalities. This is consistent with the report that estrogen may play a role in the development of the efferent ductules (Fisher et al, 1997).…”

Section: Discussionsupporting

confidence: 94%

Morphological analysis of endocytosis in efferent ductules of estrogen receptor‐α knockout male mouse

et al. 2001

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Lack of estrogen receptor (ER) results in fluid accumulation and dilation of the efferent ductules, suggesting that the role of estrogen and ER in the male reproductive tract is related to fluid reabsorption in the ductules. In the present study, endocytosis of the nonciliated cells of the efferent ductules was compared morphologically between wild type (WT) and estrogen receptor-␣ knockout (␣ERKO) male mice. The epithelial cells lining the WT efferent ductules were tall columnar in shape, whereas those of the ␣ERKO were low columnar. Immunocytochemically, the nonciliated cells of both genotypes showed positive reactions of sulfated glycoprotein-2, but the reaction products were reduced in amount in the ␣ERKO. Electron microscopy revealed that the nonciliated cells of the WT had numerous organelles for endocytosis such as coated pits and vesicles, tubules, endosomes, multivesicular bodies and lysosomes in the apical cytoplasm. These organelles were less developed in the nonciliated cells of the ␣ERKO. Morphometric analysis indicated that there was a significant reduction in area of endocytotic apparatus in the nonciliated cells of the ␣ERKO compared with that of the WT. A tracer study using gold particles demonstrated that the nonciliated cells of both WT and ␣ERKO efferent ductules were capable of taking up luminal contents. These results suggest that reabsorption of the luminal contents via endocytosis takes place in the efferent ductules but is greatly reduced in amount in the absence of ER␣.

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Section: Discussionsupporting

confidence: 94%

Morphological analysis of endocytosis in efferent ductules of estrogen receptor‐α knockout male mouse

et al. 2001

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“…Estrogen has been reported to inhibit testosterone production in porcine Leydig cells [13] and testicular tissue of rat [15], human [18], and frog [23] in vitro. EB may have a direct affect on testosterone production in Leydig cells, since ERα has been found in rat Leydig cells [6]. From the results of the present study, it remains unclear whether estrogen directly militates against testosterone production in Leydig cells.…”

Section: Discussionmentioning

confidence: 61%

“…Sci. 64(2): 107-113, 2002 It has been documented that estrogen receptor (ER) α is expressed in Leydig cells, rete testes, and efferent ducts [6], and that ERβ is expressed in Sertoli cells and spermatogenic cells [32]. Eddy et al found that testes in knockout mice lacking a functional ERα (ERKO) were atrophic with disruptions to the seminiferous epithelium and had gross dilations of the seminiferous tubule lumen in adulthood [5].…”

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confidence: 99%

Administration of Estradiol-3-Benzoate Down-Regulates the Expression of Testicular Steroidogenic Enzyme Genes for Testosterone Production in the Adult Rat.

Sakaue

Ishimura

Kurosawa

et al. 2002

The Journal of Veterinary Medical Science

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ABSTRACT. To study the role of estrogen in the testes, testosterone and testicular steroidogenic enzyme mRNA levels were investigated in male Sprague-Dawley rats 24 hr after intramuscular administration of a single dose of estradiol-3-benzoate (EB). EB administration resulted in a greater decrease in intra-testicular and serum testosterone in 10-week-old rats than in 3-or 5-week-old rats. A dose of 2 µg EB/kg had the lowest observed effect. The level of serum luteinizing hormone (LH) was unchanged at any dose. Semiquantitative RT-PCR analysis revealed that, of the four major testicular steroidogenic enzymes, mRNA levels of cytochrome P450 side-chain cleavage and 17β-hydroxysteroid dehydrogenase type-III were significantly reduced, and mRNA levels of cytochrome P450 17α-hydroxylase/ C 17-20 lyase (P450c17) were reduced severely and significantly, by EB administration. However, the level of 3β-hydroxysteroid dehydrogenase type-I mRNA was not changed. In addition, the P450c17 mRNA level in EB-treated rats was much lower than that in the testes of hypophysectomized rats, with the level in the latter being equal to that in control rats. LH is secreted into blood periodically, the effects of estrogen on the LH secretion pattern of the pituitary gland, for example, in frequency and amplitude of LH pulse, were difficult to detect with the methods of the present study. The results indicated, at least, that EB administration down-regulates P450c17 gene expression predominantly, resulting in the inhibition of testosterone production. From the differences in the steroidogenic enzyme expressions between hypophysectomized and EB-treated rats, it was suggested that EB acts on the testis directly or indirectly though not via alteration of LH secretion and induces reduction of P450c17 mRNA level. KEY WORDS: estrogen, rat, steroidogenic enzyme, testis, testosterone.J. Vet. Med. Sci. 64(2): 107-113, 2002 It has been documented that estrogen receptor (ER) α is expressed in Leydig cells, rete testes, and efferent ducts [6], and that ERβ is expressed in Sertoli cells and spermatogenic cells [32]. Eddy et al. found that testes in knockout mice lacking a functional ERα (ERKO) were atrophic with disruptions to the seminiferous epithelium and had gross dilations of the seminiferous tubule lumen in adulthood [5].Further studies on ERKO mice demonstrated that the disruption to spermatogenesis in this line was caused by a back pressure of fluid accumulating in the seminiferous tubules due to a lack of reabsorption of fluid in the efferent ductules, which were stimulated by estrogen in the normal male mouse [9]. These reports suggest that estrogen plays important roles in the male reproductive system.Testosterone plays a fundamental role in spermatogenesis and is synthesized by Leydig cells in the testicular interstitium. Estrogen inhibits testosterone production in the testes of many vertebrates, human [18], rat, frog [23], and fish [8]. Both 17β-estradiol (E 2 ) and estradiol-3-benzoate (EB), a synthetic estrogen agonist, are known to h...

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“…This finding is important given recent concerns over reported declines in human sperm counts and speculation that exposure to environmental oestrogens maybe a cause of this 8,9,29 . The extensive presence of ER (both α and β) at other sites in the male reproductive system and throughout the body 10,11,23 makes it possible that new and unexpected functions may be found for the 'female' hormone in men.…”

mentioning

confidence: 99%

A role for oestrogens in the male reproductive system

Hess

Bunick

Lee

et al. 1997

Nature

789

490

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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...

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Immunolocalisation of oestrogen receptor-α within the testis and excurrent ducts of the rat and marmoset monkey from perinatal life to adulthood

Cited by 250 publications

References 0 publications

Morphological analysis of endocytosis in efferent ductules of estrogen receptor‐α knockout male mouse

Morphological analysis of endocytosis in efferent ductules of estrogen receptor‐α knockout male mouse

Administration of Estradiol-3-Benzoate Down-Regulates the Expression of Testicular Steroidogenic Enzyme Genes for Testosterone Production in the Adult Rat.

A role for oestrogens in the male reproductive system

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