Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Equol (7-hydroxy-3[4'hydroxyphenyl]-chroman) is the major metabolite of the phytoestrogen daidzein, one of the main isoflavones found abundantly in soybeans and soy foods. Equol may be an important biologically active molecule based on recent studies demonstrating that equol can modulate reproductive function. In this study, we examined the effects of equol on prostate growth and LH secretion and determined some of the mechanisms by which it might act. Administration of equol to intact male rats for 4-7 days reduced ventral prostate and epididymal weight and increased circulating LH levels. Using binding assays, we determined that equol specifically binds 5alpha-dihydrotestosterone (DHT), but not testosterone, dehydroepiandrosterone, or estrogen with high affinity. Equol does not bind the prostatic androgen receptor, and has a modest affinity for recombinant estrogen receptor (ER) beta, and no affinity for ERalpha. In castrated male rats treated with DHT, concomitant treatment with equol blocked DHT's trophic effects on the ventral prostate gland growth and inhibitory feedback effects on plasma LH levels without changes in circulating DHT. Therefore, equol can bind circulating DHT and sequester it from the androgen receptor, thus altering growth and physiological hormone responses that are regulated by androgens. These data suggest a novel model to explain equol's biological properties. The significance of equol's ability to specifically bind and sequester DHT from the androgen receptor have important ramifications in health and disease and may indicate a broad and important usage for equol in the treatment of androgen-mediated pathologies.
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PMID:Equol is a novel anti-androgen that inhibits prostate growth and hormone feedback. 1468 Dec

Although studies in transgenic mice suggest that estrogen is important for development of the testis, very little is known about the potential role of estrogen in maturation of the primate fetal testis. Therefore, as a first step to determine whether estrogen regulates maturation of the fetal primate testis, we used immunocytochemistry to determine estrogen receptor (ER) alpha and beta expression in the fetal baboon testis. Second, we established methods to quantify ERbeta mRNA levels by competitive reverse transcription-polymerase chain reaction in Sertoli cells isolated by laser capture microdissection (LCM) from the fetal baboon testis. ERbeta protein expression was abundant in the nuclei of Sertoli, peritubular, and interstitial cells in baboon fetuses at mid (Day 100) and late (Day 165) gestation (term is 184 days). ERbeta mRNA level was 0.03 attomole/femtomole 18S rRNA in Sertoli cell nuclei and associated cytoplasm isolated by LCM. ERalpha was expressed in low level in seminiferous tubules and in moderate level in peritubular cells on Day 165. Germ cells expressed very little ERalpha or ERbeta protein, whereas the baboon fetal epididymis exhibited extensive ERalpha and ERbeta immunostaining at mid- and late gestation. In contrast to the robust expression of ERbeta, androgen receptor protein was not demonstrable within the cells of the seminiferous cords but was abundantly expressed in epididymal epithelial cells of the fetal baboon. In summary, the results of this study show that the fetal baboon testis and epididymis expressed the ERalpha and ERbeta, and we suggest that our nonhuman primate baboon model can be used to study the potential role of estrogen on maturation of the fetal testis.
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PMID:Expression of estrogen receptors alpha and beta in the fetal baboon testis and epididymis. 1503 77

In this study, two selective estrogen receptor modulators (SERMs), tamoxifen (TAM) and toremifene (TOR) or two estrogens, ethinylestradiol (EE) and diethylstilbestrol (DES) were administered to newborn male and female Sprague-Dawley rats (days 1-5) to investigate the occurrence of developmental abnormalities in the adulthood. The compounds were dosed (s.c.) at an equimolar dose of 24.9 micromol/kg. During the follow-up period, mortality occurred mainly in DES-treated male rats (3/4), associated with obstructive urinary calculi and suppurative renal inflammation in 2/3 rats. Similar lesions were not evident in other groups. At the age of 15 months, the animals were necropsied and organs were collected for histopathology and histomorphometry. Treatment-related abnormalities were restricted to the reproductive organs. Chronic prostatitis and epithelial abnormalities in the vas deferens were observed in all treatment groups. The columnar epithelium of vas deferens showed hyperplasia and development of subepithelial glandular structures resembling epididymal cysts reported in humans exposed in utero to DES. Testicular atrophy was observed especially in estrogen-treated rats. Mainly in SERM-treated female rats, the uterus showed luminal dilation or obstruction, loss of endometrial glands and myometrium disorganization including foci of muscular disruption. TOR-treated female rats showed polyp-like nodules (incidence 4/15) and a high incidence (9/15) of a simple cuboidal epithelium in cervical regions normally occupied by multilayered epithelia. In conclusion, the vas deferens is a main target organ following neonatal administration of SERMs and estrogens. In addition, female rats were significantly more susceptible to SERM treatment than to treatment with estrogens.
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PMID:Histopathology and histomorphometry of the urogenital tract in 15-month old male and female rats treated neonatally with SERMs and estrogens. 1670 47

The soy isoflavone genistein targets adipose tissue and elicits physiological effects that may vary based on dietary intake. We hypothesized that the adipose effects of genistein are dose and gender dependent. Four-week-old C57BL/6 male and female mice received daily oral doses of genistein (50-200,000 microg/kg.d) or 17beta-estradiol (E2) (5 microg/kg.d) for 15 d or a diet containing 800 ppm genistein. Genistein increased epididymal and renal fat pad and adipocyte size at doses up to 50,000 microg/kg.d or at 800 ppm in the diet in males but not in females. The alteration in adipocity correlated with changes in peripheral insulin resistance. These treatments increased genistein serum concentrations from 35+/-6 to 103+/-26 nM 12 h after treatment and lowered plasma triglycerides and cholesterol levels. The 200,000 microg/kg.d genistein dose decreased adipose tissue weight similarly to E2. This genistein dose down-regulated estrogen receptor (beta more than alpha) and progesterone receptor expression and induced estrogen-dependent adipose differentiation factors; it did not change expression of the minimal consensus estrogen-responsive element in ERE-tK-LUC mice, which was positively modulated in other tissues (e.g. the lung). E2 down-regulated almost all examined adipogenic factors. Gene microarray analysis identified factors in fat metabolism and obesity-related phenotypes differentially regulated by low and high doses of genistein, uncovering its adipogenic and antiadipogenic actions. The lower dose induced the phospholipase A2 group 7 and the phospholipid transfer protein genes; the 200,000 microg/kg.d dose inhibited them. The antiadipogenic action of genistein and down-regulation of adipogenic genes required the expression of ERbeta. In conclusion, nutritional doses of genistein are adipogenic in a gender-specific manner, whereas pharmacological doses inhibited adipose deposition.
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PMID:Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner. 1695 45

The roles of the leucine-rich repeat domain containing G protein-coupled receptor (GPCR) 4 (Lgr4), which is one of the orphan GPCRs, were analyzed with the Lgr4 hypomorphic mutant mouse line (Lgr4(Gt)). This homozygous mutant had only one-tenth the normal transcription level; furthermore, 60% of them survived to adulthood. The homozygous male was infertile, showing morphologic abnormalities in both the testes and the epididymides. In the testes, luminal swelling, loss of germinal epithelium in the seminiferous tubules, and rete testis dilation were observed. Cauda epididymidis sperm were immotile. Rete testis dilation was due to a water reabsorption failure caused by a decreased expression of an estrogen receptor (ESR1) and SLC9A3 in the efferent ducts. Although we found differential regulation of ESR1 expression in the efferent ducts and the epididymis, the role of ESR1 in the epididymis remains unclear. The epididymis contained short and dilated tubules and completely lacked its initial segment. In the caput region, we observed multilamination and distortion of the basement membranes (BMs) with an accumulation of laminin. Rupture of swollen epididymal ducts was observed, leading to an invasion of macrophages into the lumen. Male infertility was probably due to the combination of a developmental defect of the epididymis and the rupture of the epithelium resulting in the immotile spermatozoa. These results indicate that Lgr4 has pivotal roles to play in the regulation of ESR1 expression, the control of duct elongation through BM remodeling, and the regional differentiation of the caput epididymidis.
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PMID:LGR4 regulates the postnatal development and integrity of male reproductive tracts in mice. 1707 37

We report the clinical, morphological and immunohistochemical findings of a case with non-papillary serous cystadenoma of the epididymis. The tumor was a unilocular cyst with a thin fibrous capsule, lined by cuboidal or columnar epithelium containing ciliated cells, mostly arranged in a single layer. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) AE1/AE3 and epithelial membrane antigen (EMA), strongly positive for CK7, progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), vimentin, CA-125 and S-100 protein. The cells did not stain for CK20 and CD10. Morphological and immunohistochemical features suggested a mullerian differentiation, possibly originated from vestigial remnants of the Muller duct. This tumor is one of the rare benign lesions which should be considered in the differential diagnosis of a swelling in the epididymal region.
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PMID:Serous cystadenoma of the epididymis of common epithelial ovarian type: case report with an immunohistochemical study. 1731 78

Maturation of sperm within the epididymis is a pre-requisite for fertilization in mammals. Epididymal function is controlled by a complex array of hormones and growth factors. While testosterone is the primary stimulus for epididymal development and sperm maturation, the importance of estrogen effects on efferent ductules has been increasingly recognized, and points to a need to clarify the role of estrogen receptor-mediated action in the epididymis. Estrogens modulate the expression of genes involved in fluid absorption in the efferent ductules and the epididymis. The present review highlights the role of estrogen in regulation of epididymal gene expression.
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PMID:Delineating the role of estrogen in regulating epididymal gene expression. 1756 59

The estrogen receptor-alpha knockout (ERalphaKO, ERalpha-/-) mice were generated via the Cre-loxP system by mating floxed ERalpha mice with beta-actin (ACTB)-Cre mice. The impact of ERalpha gene deletion in the male reproductive system was investigated. The ACTB-Cre/ERalpha(-/-) male mice are infertile and have lost 90% of epididymal sperm when compared with wild-type mice. Serum testosterone levels in ACTB-Cre/ERalpha(-/-) male mice are 2-fold elevated. The ACTB-Cre/ERalpha(-/-) testes consist of atrophic and degenerating seminiferous tubules with less cellularity in the disorganized seminiferous epithelia. Furthermore, the ventral and dorsal-lateral prostates of ACTB-Cre/ERalpha(-/-) mice display reduced branching morphogenesis. Loss of ERalpha could also be responsible for the decreased fibroblast proliferation and changes in the stromal content. In addition, we found bone morphogenetic protein, a mesenchymal inhibitor of prostatic branching morphogenesis, is significantly up-regulated in the ACTB-Cre/ERalpha(-/-) prostates. Collectively, these results suggest that ERalpha is required for male fertility, acts through a paracrine mechanism to regulate prostatic branching morphogenesis, and is involved in the proliferation and differentiation of prostatic stromal compartment.
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PMID:Defects of prostate development and reproductive system in the estrogen receptor-alpha null male mice. 1875 2

p-tert-Octylphenol (OP) is a degradation product of alkylphenol ethoxylates. OP is an endocrine disruptor known to bind to the estrogen receptor; however, effects on males are controversial. The objective of this study was to evaluate the effects of chronic exposure to OP on male reproduction. Adult Sprague-Dawley rats were administered OP for 60 d, representing 1.5 cycles of spermatogenesis. Experimental groups included a vehicle control, and three doses of OP (25, 50, or 125 mg/kg body weight [bw]) administered daily by gavage. There was a significant decrease in body weight in the 125-mg/kg group after 60 d of treatment. Both testicular and epididymal weights and histology were not altered by treatment with OP at any of the doses administered. There were no marked differences in cauda epididymal sperm counts at any doses; however, total percent sperm motility was significantly lower in rats exposed to the intermediate dose (50 mg/kg bw). There was an increase in percent static sperm cells in all OP-treated groups, with the intermediate dose (50 mg/kg) displaying a significantly higher proportion of static cells relative to untreated controls. Caput epididymal sperm motility was unaltered by OP treatment. Gene expression profiles of testes from control and high-dose-exposed rats indicate that 14 genes were modulated by at least twofold, although these changes were not statistically significant. Taken together, results from this study indicate that OP treatment of adult rats does not appear to exert major effects on male reproductive endpoints at relevant environmental exposure doses.
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PMID:Effects of chronic exposure to octylphenol on the male rat reproductive system. 2007 29

Basigin plays important roles in both male and female reproduction because basigin (Bsg) null male and female mice are infertile. The aim of the present study was to determine whether basigin expression in reproductive organs requires estrogen receptor-alpha (ESR1, ERalpha) or -beta (ESR2, ERbeta). Expression of basigin protein in the testis, ovary, and male and female reproductive tracts was studied in adult wild-type (WT), Esr1-null (alphaERKO), and Esr2-null (betaERKO) mice by immunohistochemistry and immunoblotting. Basigin mRNA levels in ovary and uterus were examined by quantitative RT-PCR. In females, basigin protein expression was observed mainly in granulosa and interstitial cells of the ovary and epithelial cells of the proximal oviduct in all genotypes. Basigin protein was also expressed in the uterine epithelium at proestrus and estrus in WT and betaERKO mice but not in alphaERKO mice. However, a higher level of basigin mRNA was observed in uteri of alphaERKO mice compared with WT and betaERKO mice. In males, basigin was expressed in Leydig cells and all germ cells except spermatogonia in all genotypes. Basigin was present in epithelial cells lining the efferent ductules in WT and betaERKO mice, but expression was greatly reduced in alphaERKO mice. In epididymal ducts, basigin expression was observed in epithelial cells in the caput and cauda in all genotypes. These data suggest that expression of basigin protein requires ESR1, but not ESR2, in the uterus and efferent ductules, but is independent of estrogen receptor in the ovary, oviduct, testis, and epididymis.
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PMID:Expression of basigin in reproductive tissues of estrogen receptor-{alpha} or -{beta} null mice. 2038 36


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