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)

The effects on the fertility of adult male rats of six new synthetic steroids: I, 3-cyano-5alpha-androst-1-en-17-one; II, the 17beta-acetate form of I; III, 17beta-hydroxy-5beta-cyano-androstan-3-one; IV, 6-methylpregnenolone; V, 17beta-hydroxy-17alpha-ethynyl-5beta-cyano-19-norandrostan-3-one; and VI, 19-norspiroxenone (oestr-4-en-3-one-spiro-17alpha-2'-[tetrahydrofuran]) have been tested. After 6 weeks of treatment with daily doses of 5 mg (I, II, III), 15 mg (IV) or 10 mg (V, VI) only steroid VI blocked the completion of spermatogenesis and reduced the number of foetuses sired in at least five females/male. Steroid VI also diminished seminal vesicular, prostatic, testicular and epididymal weights. It inhibited the testicular enzymes, 3beta-hydroxysteroid dehydrogenase-delta4-5-3-oxosteroid isomerase system, 17alpha-hydroxylase, and C17-20 lyase markedly, but did not affect the adrenal dehydrogenase-isomerase system. It depressed, strikingly, testicular and serum levels of testosterone and 5alpha-dihydrotestosterone and reduced pituitary and serum levels of FSH and LH. Although marked depression of target organ weights also occurred with steroids II, IV and V, and reduction of androgen levels and LH in the circulation with III, IV and V, only VI was a potent blocker of male fertility with the exception of a slight block of the siring of viable foetuses by steroids IV and V. The major difference in site of action of steroid VI from the others was the depression of pituitary and serum levels of FSH along with a marked diminution of testicular content of both testosterone and 5alpha-dihydrotestosterone. 19-Norspiroxenone in the rat is a potent anti-oestrogen without inherent oestrogenicity and is anti-uterotrophic. Thus, VI may affect male fertility by virtue of its potent anti-oestrogenic action in the hypothalamus or testis.
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PMID:Effects of new multi-site hormone blockers on the fertility of male rats. 127 Sep 48

We have investigated the effects of two 4-ene-steroid 5 alpha-reductase inhibitors, diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA) and (4R)-5,10-seco-19-norpregna-4, 5-diene-3,10,20-trione (SECO), on testicular and epididymal androgen biosynthesis. Kinetic analyses revealed that both compounds inhibited epididymal DHT biosynthesis. 4-MA was a competitive inhibitor of epididymal nuclear and microsomal 4-ene-steroid 5 alpha-reductases (3-oxo-5 alpha-steroid: NADP 4-ene-oxidoreductase EC 1.3.1.22) with Kiapp values of 12.8 and 15.1 nmol/l compared to the respective Kmapp values of 185 and 240 nmol/l. Values for the Vmaxapp were always within 70-130% of the control. SECO at 1.0 mumol/l, also inhibited epididymal nuclear and microsomal 4-ene-steroid-5 alpha-reductases, causing respectively 2.9 and 5.2-fold increases in Kmapp. The Vmaxapp values were unchanged. However, SECO concentrations of 5 and 25 mumol/l abolished 4-ene-steroid 5 alpha-reductase activity at all testosterone concentrations. To examine the specificity of these compounds, we investigated their effects on the enzymes that convert pregnenolone to testosterone. Rat testis microsomes converted pregnenolone to testosterone via the 4-ene-3-oxo pathway, with the major metabolites being progesterone, 17-hydroxyprogesterone, 4-androstenedione and testosterone; some 17-hydroxypregnenolone was also formed. Very small amounts of dehydroepiandrosterone (DHA) and 5-androstenediol were detected. SECO, at a concentration that completely inhibited epididymal 4-ene-steroid 5 alpha-reductase activity, did not alter the metabolic profile of pregnenolone metabolism. However, 4-MA prevented the appearance of 4-ene steroids, and large quantities of 17-hydroxypregnenolone and DHA accumulated, suggesting that inhibition of the 3 beta-hydroxysteroid: NAD(P)+ oxidoreductase (EC 1.1.1.51) and 3-oxosteroid 5-ene-4-ene-isomerase (EC 5.3.3.1) [3 beta-hydroxysteroid dehydrogenase-isomerase] was occurring. Optimal conditions for the microsomal conversion of DHA to 4-androstenedione were determined; kinetic analyses of the 3 beta-hydroxysteroid dehydrogenase-isomerase activity revealed that 4-MA inhibited this reaction non-competitively, reducing Vmaxapp values to 25% of the control. The Kiapp determined from the intercept replot, was 121 nmol/l, and the Kmapp was always between 90 and 130% of the control value. It is concluded that SECO is more specific than 4-MA in its effects on androgen biosynthesis in the testis and epididymis and that both these drugs should provide useful tools in assessments of the relative contributions of 5 alpha-reduced androgens to androgen dependent processes.
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PMID:The effects of diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA) and (4R)-5,10-SECO-19-norpregna-4,5-diene-3,10,20-trione (SECO) on androgen biosynthesis in the rat testis and epididymis. 370 62

Isoproturon, a nonhalogenated substituted phenylurea herbicide, was evaluated for its cumulative toxic effects on testicular histomorphology., steroid hormone biosynthesis-related enzymes, spermatogenesis and sperm cells in adult albino rats. The compound, suspended in refined groundnut oil, was administered (po) to rats for 10 weeks @ 0,200, 400 and 800 mg/kg/day for 6 days/week. Isoproturon, at 800 mg/kg dose, decreased epididymal sperm count and percentage of motile sperms and increased the percentage of morphologically abnormal sperm cells. At the same dose, diameter of seminiferous tubules was reduced, number of tubules per microscopic field was increased and the percentage of tubules with evidence of spermatogenesis decreased. However, the percentage of damaged tubules was increased with 400 and 800 mg/kg doses. Histoenzymological observations revealed dose-related reduction in the activities of glucose-6-phosphate dehydrogenase and delta 5-3 beta-hydroxy steroid dehydrogenase. Activity of 17 beta-hydroxy steroid dehydrogenase was not affected appreciably. Overall findings suggest that isoproturon, at high dose, impairs androgen biosynthetic process, affects spermatogenesis and induces maturational anomalies of sperm cells in rat.
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PMID:Effect of isoproturon on male reproductive system: clinical, histological and histoenzyonological studies in rats. 931 20

Glutathione S-transferases (GSTs), a family of isoenzymes, catalyze the conjugation of glutathione to a variety of electrophiles, and protect cellular constituents from electrophilic and oxidative attack. Aging is associated with an overall increase in oxidative stress and thus free radical production. The present study examines the immunocytochemical localization of Ya, Yc, Yb1, Yb2, Yo, and Yf GST subunits in the testis and epididymis of Brown Norway rats aged 3, 12, 18, and 24 months. In the testis, neither Sertoli nor germ cells showed changes in the GST staining pattern during aging. At 24 months, two types of Leydig cells were noted. Some (peritubular) formed a distinct band at the periphery of the tubule while others were seen in the interstitial space. The peritubular cells were identified as Leydig cells by specific staining for 3beta-hydroxysteroid dehydrogenase (3beta-HSD), a Leydig cell-specific marker. Both types of Leydig cells were intensely reactive for all GST subunits at all ages. In the epididymis, principal cells of all epididymal regions, except the proximal cauda region, showed no changes in GST expression at all ages examined. At 24 months, some principal cells of this region became greatly enlarged and vacuolated. These cells were unreactive for Yo, Yb1, Yb2, and Yc, while adjacent normal-appearing principal cells maintained the same intensity of expression as seen in 3-month controls. In contrast, vacuolated principal cells were reactive for the Ya subunit, while adjacent normal principal cells were unreactive. These data indicate that selective changes occur in the expression of GSTs at 24 months in principal cells having both a normal and a vacuolated appearance. The underlying mechanism responsible for these changes with age is unresolved, but we speculate that they lose the ability to handle oxidative stress. Taken together, these data show that aging affects region-specific changes in GST expression in the epididymis and Leydig cell distribution in the testis.
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PMID:The effects of aging on the expression of glutathione S-transferases in the testis and epididymis of the Brown Norway rat. 973 48

Adult male rats previously exposed on gestation days (GD) 12-21 to di(n-butyl) phthalate (DBP) have reproductive tract malformations, particularly agenesis of the epididymis, decreased sperm production, and Leydig cell hyperplasia and adenomas. Although similar effects are produced by the potent androgen receptor (AR) antagonist flutamide and are indicative of disruption of male sexual differentiation via an antiandrogenic mechanism, DBP is not an AR antagonist. The purpose of the study was to determine whether DBP causes pathologic changes and alterations in androgen status in the testis during the prenatal period of male reproductive tract differentiation. Pregnant CD rats were given corn oil, DBP (500 mg/kg/day), or flutamide (100 mg/kg/day) p.o. on GD 12-21. At GD 16-21, DBP caused hyperplasia of Leydig cells, many of which were 3beta-hydroxysteroid dehydrogenase- and/or AR-positive. Focal areas of hyperplasia had increased numbers of Leydig cells positive for proliferating cell nuclear antigen (PCNA). At GD 21, testis atrophy was apparent, seminiferous cords in DBP-exposed fetuses were enlarged and contained multinucleated gonocytes that, unlike controls, were PCNA-positive. DBP, but not flutamide, markedly decreased testicular testosterone levels at GD 18 and 21. Fewer epididymal ducts and reduced AR staining in some ducts were evident with DBP treatment, whereas decreased overall AR staining was seen with flutamide in the presence of mild Leydig cell hyperplasia. Leydig cell proliferation is likely a compensatory mechanism to increase testicular steroidogenesis triggered by testosterone insufficiency. The overall decrease in androgen concentration is not corrected and results in reproductive tract malformations. The multinuclearity and proliferation of gonocytes suggests an underlying Sertoli cell dysfunction.
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PMID:Fetal testosterone insufficiency and abnormal proliferation of Leydig cells and gonocytes in rats exposed to di(n-butyl) phthalate. 1193 29

Studies were performed on the rat epithelial cells of the caput and cauda epididymidis cultured in a full medium enriched with foetal calf serum without or with exogenous testosterone. After 3 days of culture, the cells formed a monolayer. The cytoplasm of epididymal epithelial cells cultured with testosterone was rich in lipid droplets, glycogen and PAS-positive substances, while their content was decreased in the cytoplasm of cells cultured without testosterone. The activity of 3beta-hydroxysteroid dehydrogenase was observed both in the cytoplasm of cultured epididymal epithelial cells and epithelial cells of epididymal sections. Hormone assays showed very low levels of dehydroepiandrosterone, androstenedione and testosterone, and the absence of progesterone in the media of cells cultured without testosterone and higher testosterone concentrations when the cells were cultured with exogenous testosterone. However, the concentration of 17beta-oestradiol found in the medium of cells was high, and exceeded many-fold its levels in the control media. Lentaron (Formestan), steroidal inhibitor of cytochrome P450 aromatase added to the culture decreased the secretion of oestradiol. RT-PCR analysis yielded cDNA products of 333 bp in length when primers were chosen to amplify a highly conserved sequence in the 3' region of the cytochrome P450 aromatase gene. This study demonstrates the ability of epididymal epithelial cells in vitro to synthesize androgens and mRNA for cytochrome P450 aromatase in the cultured epididymal epithelial cells of the rat as well as the ability to aromatise the synthesized androgen to 17beta-oestradiol.
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PMID:Primary culture of the rat epididymal epithelial cells as a source of oestrogen. 1205 15

This study examined the effect of sodium fluoride, a water pollutant important through the world, including India, on testicular steroidogenic and gametogenic activities in relation to testicular oxidative stress in rats. Sodium fluoride treatment at 20mg/kg/day for 29 days by oral gavage resulted in significant diminution in the relative wet weight of the testis, prostate, and seminal vesicle without alteration in the body weight gain. Testicular delta(5),3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD activities were decreased significantly along with significant diminution in plasma levels of testosterone in the fluoride-exposed group compared to the control. Epididymal sperm count was decreased significantly in the fluoride-treated group and qualitative examination of testicular sections revealed fewer mature luminal spermatozoa in comparison to the control. The seminiferous tubules were dilated in treated animals. Fluoride treatment was associated with oxidative stress as indicated by an increased level of conjugated dienes in the testis, epididymis, and epididymal sperm pellet with respect to control. Peroxidase and catalase activities in the sperm pellet were decreased significantly in comparison to the control. The results of this experiment indicate that fluoride at a dose encountered in drinking water in contaminated areas exerts an adverse effect on the male reproductive system and this effect is associated with indicators of oxidative stress.
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PMID:Testicular toxicity in sodium fluoride treated rats: association with oxidative stress. 1222 May 99

Seasonal changes in spermatogenesis of Japanese lesser horseshoe bats, Rhinolophus cornutus, captured in Aomori Prefecture (Japan) were examined by light microscopy. In March, the seminiferous tubules revealed almost no lumen. The seminiferous epithelium consisted of Sertoli cells and spermatogonia. The interstitium occupied a relatively large area. In June, the seminiferous tubules gradually increased in diameter. Lumen was clearly seen at the center of seminiferous tubules. Mitotic figures of spermatogonia and spermatocytes were occasionally recognized. Interstitium occupation was still abundant. In August, the diameter of seminiferous tubules maximized. The interstitium occupied only a small area. Active spermatogenesis was obvious at this time. Released spermatozoa were frequently observed within the expanded lumen. In October, although spermatogenesis was still active, the diameter of seminiferous tubules tended to decrease in size. In December, active spermatogenesis completely disappeared. The diameter of tubules greatly decreased. In most cases, the seminiferous epithelium contained only Sertoli cells and spermatogonia. Thus, spermatogenesis in Japanese lesser horseshoe bats occurs from the middle or late summer to the middle autumn in Aomori Prefecture. In epididymal tracts, aggregated spermatozoa were recognized throughout the year. The cytoplasm of all Leydig cells in the interstitium was positive for 3beta-hydroxysteroid dehydrogenase throughout the year.
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PMID:Seasonal changes in spermatogenesis of the Japanese lesser horseshoe bat, Rhinolophus cornutus from a morphological viewpoint. 1248 43

This study concerned the minimum and optimum effective doses of calcium chloride needed for induction of chemosterilization in male albino rats, 30 days after a single intratesticular injection of calcium chloride (CaCl2.2H2O) solution at 2.5, 5, 10 or 20 mg per 100 g body weight per testis. There was a significant diminution in the relative wet weight of the sex organs (p<0.01), epididymal sperm count (p<0.001), plasma concentration of testosterone (p<0.01), testicular activities of delta5,3beta-hydroxy steroid dehydrogenase (delta5,3beta-HSD), 17beta-hydroxy steroid dehydrogenase (17beta-HSD) (p<0.01), glutathione S-transferase (GST) (p<0.01), superoxide dismutase (SOD) (p<0.01), and peroxidase (p<0.01), significant elevations in testicular content of malondialdehyde (MDA) and conjugated dienes (p<0.01), along with derangement of seminiferous tubular architecture and degeneration of the Leydig cells in the testis and elevations in the concentrations in the plasma of LH and FSH (p<0.01), commencing at a dose of 5 mg, with the greatest effects at a dose of 20 mg. No significant alterations in these factors occurred at the dose of 2.5 mg in comparison to the control that received only the vehicle. There was no significant alteration in the plasma concentrations of prolactin (p>0.05), corticosterone (p>0.05) or fasting blood glucose or in the rectal temperature (p>0.05) at any of the doses relative to the control group, suggesting that this chemosterilizing procedure did not exert any chronic stress on the experimental animals. From these observations, it may be suggested that 5 mg should be considered as the minimum dose, and 10 mg or 20 mg as the optimum dose, whereas 2.5 mg was ineffective for induction of chemosterilization. There would seem to be little point in using more than 20 mg of calcium chloride for this purpose. Intratesticular injection of calcium chloride at an effective dose may be considered as an alternative to surgical castration.
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PMID:Dose-dependent response to an intratesticular injection of calcium chloride for induction of chemosterilization in adult albino rats. 1250 39

Fenvalerate (Fen) is a synthetic pyrethroid, which is commonly used for destroying a variety of insect pests damaging several vegetable, fruit, and cotton crops. This insecticide is also used to mitigate household insects like flies, cockroaches, mosquitoes, and so forth. Human beings are exposed to formulated Fen preparations mostly by inhalation during spraying in fields for crop protection, for control of household insects, and also during handling and packaging at manufacturing plants. Limited online information is available regarding toxic effects of formulated Fen exposure on mammalian reproductive system. The present study has been undertaken to investigate male reproductive toxic effects of a formulated preparation of Fen (20% EC) particularly in relation to steroidogenic alterations in testes and sera of rats exposed by nose-only inhalation for (4 hours/day and five days a week) for three months. The results indicate significant reduction in the weight of testes, epididymal sperm counts, and sperm motility, along with decrease in marker testicular enzymes for testosterone biosynthesis viz. 17-beta-hydroxy steroid dehydrogenase (17-beta-HSD) and glucose-6-phosphate dehydrogenase (G6PDH), leading to net decrease in serum testosterone concentration in group of rats exposed to one-fifth LC50 of Fen (20% EC) by inhalation (4 hours/day, five days a week) subchronically for three months. These results for the first time indicate the role of testosterone in Fen (20% EC)-induced male reproductive toxicity of rats subchronically exposed by inhalation probably due to neuroendocrine-mediated phenomenon and hormone-disrupting property of the insecticide.
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PMID:Steroidogenic alterations in testes and sera of rats exposed to formulated Fenvalerate by inhalation. 1250 54


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