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...

Previous studies of the estrogen receptor-alpha knockout (alpha ERKO) in the male mouse demonstrate that the rete testis and efferent ductules are targets of estrogen. Because the alpha ERKO mouse lacks a functional estrogen receptor alpha (ER alpha) throughout development, it was not known whether the morphological and physiological abnormalities observed in the alpha ERKO male were due to developmental defects or to dysfunctions concurrent with the lack of ER alpha in the tissue. This study was designed to determine if treatment of normal wild-type (WT) mice with the pure antiestrogen, ICI 182,780, (ICI) could reproduce the morphological characteristics seen in alpha ERKO mice. Thirty-day-old male mice were treated for 35 days with either castor oil or ICI. Age-equivalent alpha ERKO mice were used for comparison. Light microscopic examinations of the reproductive tracts revealed dramatic changes in the efferent ductules of treated mice: a 1.7-fold increase in luminal diameter, a 56% reduction in epithelial cell height, a 60% reduction in brush boarder height of nonciliated cells, and an apparent reduction of the number of observable lysosomes and endocytotic vesicles. Testes of ICI-treated mice showed swollen rete testes area (6.5 times larger than control) and a 65% reduction in rete testis epithelium height. However, there were no significant changes in body and testis weights. These results indicate that ER blockage with ICI in WT mice results in morphological changes of the efferent ductules resembling those seen in alpha ERKO siblings of the same age. Based on this study, we conclude that ER alpha has a functional role in the mouse reproductive tract and the aberrant morphology observed in the efferent ductules of the alpha ERKO mouse is likely the result of a concurrent response to the lack of functional ER alpha, and not solely due to the lack of ER alpha during early developmental times.

No 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...

We investigated the effects of estrogen on global myocardial ischemia-reperfusion injury in rats that were ovariectomized (Ovx), sham-operated, or ovariectomized and then given 17beta-estradiol (E(2)beta) supplementation (Ovx+E(2)beta). Hearts were excised, cannulated, perfused with and then immersed in chilled (4 degrees C) cardioplegia solution for 30 min, and then retrogradely perfused with warm (37 degrees C), oxygenated Krebs-Henseleit bicarbonate buffer for 120 min. The coronary flow rate, first derivative of left ventricular pressure, and nitrite production were all significantly lower in Ovx than in sham-operated or Ovx+E(2)beta hearts. However, coronary flow rates or nitrate production were not consistently different throughout the entire reperfusion period. Ca(2+) accumulated more in Ovx rat hearts than in sham-operated or Ovx+E(2)beta hearts, and mitochondrial respiratory function was lower in Ovx hearts than in hearts from the other two groups. Marked interstitial edema and contraction bands were seen in hematoxylin-eosin-stained sections of Ovx rat hearts but not in hearts from either of the other groups. Hematoxylin-basic fuchsin-picric acid-stained sections revealed fewer viable myocytes in hearts from the Ovx group than from the sham or Ovx+E(2)beta group. Transmission electron microscopy demonstrated more severely damaged mitochondria and ultrastructural damage to myocytes in Ovx rat hearts. Our results indicate that estrogen plays a cardioprotective role in global myocardial ischemia-reperfusion injury in female rats.

The purpose of the present investigation was to measure the concentrations of progesterone (P4), testosterone (T) and estradiol-17 beta (E2) in isolated theca and granulosa layers of the five preovulatory follicles of the domestic hen. The largest follicle (F1), the second largest (F2), third largest (F3), fourth largest (F4) and fifth largest (F5) follicles were removed at 24, 18, 12, 6 and 2 h before the expected ovulation. Theca and granulosa layers were isolated and P4, T, E2 and protein concentrations determined. Protein concentrations of the granulosa and theca layers increased 5- and 15-fold, respectively, during the five ovulatory cycles prior to ovulation. As the follicle approached ovulation, there was a linear decrease in E2 concentration of the theca layer with the most significant decrease (P less than 0.001) occurring between 24 and 18 h of the ovulatory cycle. In the F3 and F4 theca layers, there was a significant increase (P less than 0.005) in E2 at 6 h of the ovulatory cycle. Fluctuations in T concentrations in theca and granulosa layers were similar. There was a significant increase (P less than 0.05) in T in both layers of the F2, F3 and F4 follicles at 6 h followed by a decrease (P less than 0.005) in the theca layers at 2 h of the ovulatory cycle. The P4 concentration of the granulosa layer increased gradually during follicular maturation, with the greatest increase occurring in the F2 and F1 granulosa layers between 18 and 12 h of the ovulatory cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

The high mortality rate due to ovarian cancer is attributed to the lack of an effective early detection method. Due to the non-specificity of symptoms at early stage, most of the ovarian cancer cases are detected at late stages. This makes the access to women with early stage disease problematic and presents a barrier to development and validation of tests for detection of early stage of ovarian cancer in humans. Animal models are used to elucidate disease etiologies and pathogenesis that are difficult to study in humans. Laying hen is the only available animal that develops ovarian cancer spontaneously; however, detail information on ovarian tumor histology is not available. The goal of this study was to determine the histological features of malignant ovarian tumors in laying hens. A total of 155 young and old (1-5 years of age) laying hens (Gallus domesticus) were selected randomly and evaluated gross and microscopically for the presence of ovarian tumors. Histological classification of tumors with their stages and grades were performed with reference to those for humans. Similar to humans, all four types including serous, endometrioid, mucinous and clear cell or mixed carcinomas were observed in hen ovarian tumors. Some early neoplastic as well as putative ovarian lesions were also observed. Similarities in histology, metastasis and stages of hen ovarian cancer to those of humans demonstrate the feasibility of the hen model for additional delineation of the mechanism underlying ovarian carcinogenesis, preclinical testing of new agents for the prevention and therapy of this disease. Keywordsovarian cancer; preclinical model; laying hen; tumor histology Ovarian cancer (OVCA) is a fatal disease of women with the highest mortality rate of all gynecological malignancies. Approximately 70% of women with OVCA die of this disease (1,2). Survival is high in women who present with early stage disease(3,4). The lack of specific symptoms, the relative inaccessibility of the ovaries deep in the pelvis, and the absence of NIH Public Access Author ManuscriptInt J Gynecol Cancer. Author manuscript; available in PMC 2010 May 1. Published in final edited form as:Int J Gynecol Cancer. 2009 May ; 19(4): 531-539. doi:10.1111/IGC.0b013e3181a41613. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript specific marker(s) represent barriers for early detection (5,6). In most cases, OVCA is diagnosed at a late stage(3). Furthermore, our understanding of the early pathogenesis of OVCA has been hindered by the lack of sufficient number of patients with early stage disease (3,4,7). Animal models are used to elucidate disease etiologies and pathogenesis that are difficult to study in humans. Although large domestic mammals including bovine have similar reproductive traits and develop OVCA spontaneously similar to humans, the low incidence rate, multiple pregnancies, longer gestation and lactation period make them an inappropriate model for human OVCA. On the other hand, a number of rodent models, induced or g...

Estrogen production within the testis has been a subject of considerable controversy for many years. Several studies have shown that both Sertoli and Leydig cells produce estrogen during different stages of development. Therefore, we have conducted experiments to localize aromatase, a cytochrome P450 enzyme that converts androgen to estrogen, within the testis. First, P450 aromatase (P450arom) was localized in germ cells of the adult mouse testis by immunocytochemistry, using an antiserum generated against purified human placental cytochrome P450arom. In the germinal epithelium, P450arom was located primarily in the Golgi region of round spermatids, throughout the cytoplasm of elongating spermatids, and along the flagella of late spermatids. Second, localization of P450arom within the germinal epithelium was supported by Western blot analysis of isolated germ cells. Third, Northern blot analysis using a mouse P450arom cDNA probe indicated that the mRNA for the mouse P450arom was present in testicular germ cells. Fourth, P450arom activity was measured in germ cells by the 3H2O water assay. Based upon these observations, we conclude that germ cells are a site of estrogen synthesis in the adult mouse testis.