Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.20 (alpha-glucosidase)
4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Results from recent animal models with implications for putative human male contraceptives acting on the epididymis are reviewed. Inducing sterility by enhancing sperm transport through the epididymis has not been achieved. The induction of infertility in males of several species is easier to achieve by direct actions of drugs on sperm function (e.g. inhibition of sperm-specific isoenzymes of the glycolytic pathway by chloro-compounds) than by indirectly reducing amounts of epididymal secretions normally present in high concentration (e.g. alpha-glucosidase, L-carnitine). The former show promise for the clinic since human spermatozoa are susceptible to inhibition. On the other hand, the infertile male mice of the c-ros knock-out model demonstrate the influence of even a small region of the epididymis on fertility, so that targeting the as yet unknown epididymal factors presumably secreted in limiting amounts by this epididymal segment, is a new lead for a contraceptive. Targeting a specific sperm protein acquired in the testis, but depleted in the epididymis by toxicants that induce rapid infertility, may also lead to the discovery of new contraceptives, but these will require developing new means of organ-specific delivery of contraceptive drugs.
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PMID:Recent biochemical approaches to post-testicular, epididymal contraception. 1033 18

The human epididymis and its secretions actively promote sperm fertilizing capacity and provide protection for spermatozoa against harmful influences. Among epididymal secretions, glycosidases have been recently studied and associated with molecular changes on the sperm surface. In the present work, we studied the influence of different concentrations of testosterone, dihydrotestosterone and cyproterone acetate on the secretion of alpha-glucosidase, N-acetyl-glucosaminidase, beta-glucuronidase and alpha-mannosidase by isolated and cultured epithelial cells from human caput, corpus and cauda epididymides. Cell cultures were obtained from aggregates of isolated tubule fragments plated on extracellular matrix-covered multi-well plates. Activities of the glycosidases were measured in conditioned culture media and were higher in the distal regions of the epididymis. Testosterone and dihydrotestosterone significantly increase the enzyme secretion in a concentration-dependent manner. This increase was higher in corpus and/or cauda than in caput epididymis. Cyproterone acetate caused a dose-dependent decrease in glycosidase secretion in cultures from all epididymal regions. It is concluded that the secretion of epididymal glycosidases is regulated by androgen, being stimulated by dihydrotestosterone and testosterone and inhibited by the androgen antagonist cyproterone acetate.
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PMID:Androgen regulation of glycosidase secretion in epithelial cell cultures from human epididymis. 1035 69

alpha-Glucosidase is a normal constituent of human semen, produced mainly in the epididymis. It is significantly correlated to sperm count. Its activity is low in cases of epididymal obstruction. We evaluated alpha-glucosidase activity in 653 semen samples of patients, who attended our department for marital infertility, with respect to associations to clinical and other seminal parameters. The normal range (mean +/- 2 SD) in samples with normal parameter values was 7.2-46.4 mU ml-1. The determination in patients with azoospermia revealed mean values of 7.7 +/- 9.5 mU ml-1 in obstructive azoospermia, and 15.8 +/- 11.5 mU ml-1 in nonobstructive azoospermia. The difference was not statistically significant in that the sensitivity of determination with respect to the presence of obstruction was only 0.66, and the specificity 0.83. A significant correlation (r = 0.34) of alpha-glucosidase activity with log sperm count was observed. The mean alpha-glucosidase activity was not significantly different in groups formed according to sperm motility, according to leucocyte count or according to semen volume. A difference between smokers and nonsmokers with comparable sperm count, as reported in the literature, did not occur. We conclude from our results that the determination of alpha-glucosidase activity does not give additional information of the fertility status exceeding that of other clinical investigations or parameters of semen analysis.
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PMID:Why do we determine alpha-glucosidase activity in human semen during infertility work-up? 1052 38

The effects of atrazine exposure on testicular sperm number, epididymal sperm number and motility and alpha-glucosidase activity in the epididymis were studied in Fischer rats. Histological changes in the testicular tissue were followed by light and electron microscopy. Groups of adult animals were treated i.p. with 60 and 120 mg atrazine kg(-1) body wt. twice a week over 60 days. The results indicate a decrease in the body weight and relative weights of pituitary and ventral prostate vs control, measured on the last day of treatment in both treated groups. Testicular sperm number (expressed as number of sperm per 500 Sertoli cells) in atrazine-treated groups increased with the treatment time due to the reduced sperm motility. Therefore atrazine treatment provoked a significant decrease in sperm number and motility in epididymis, measured after the last day of treatment. alpha-Glucosidase activity in the epididymis, after the last day of treatment, showed a decrease in both treated groups vs control values. Histological analysis of testicular tissue from treated rats showed the cell disorganization and cell clusters together with spermatocytes. Electron microscopy presented differently vacuolated cytoplasm, collagen fibre was reduced, Leydig cells were of irregular shape with unequal form and cisternae of rough endoplasmic reticulum were accentuated and softly widened. In Sertoli cell cytoplasm, atrazine treatment provoked degenerative changes. According to the results obtained, it is evident that atrazine exerted morphological changes and a toxic effect on sperm and their motility.
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PMID:Disorders of male rat reproductive tract under the influence of atrazine. 1064 Oct 17

The dynamics of glycosidase secretion was evaluated in human epididymal cell culture. Epithelial cells from caput, corpus, and cauda epididymis were isolated from tissue obtained from patients undergoing therapeutic orchidectomy due to prostatic carcinoma. The activities of alpha-glucosidase, N-acetylglucosaminidase, beta-glucuronidase, and alpha-mannosidase were analyzed in conditioned culture media. Glycosidase activity was significantly higher in corpus and/or cauda than in caput epididymis. There was a time-dependent increase in enzyme activities that was maximal between 10 and 14 days of culture in all epididymal regions. Epididymal glycosidases are secreted by cultured epithelial cell from human epididymis with an increase toward the distal regions of this organ, which may be related to the dynamics of sperm maturation. Cultures from different epididymal regions may represent a valuable tool to study of human epididymal function.
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PMID:Secretion of glycosidases in human epididymal cell cultures. 1095 1

The induction of infertility in males of several species through epididymal interference is more difficult to achieve by reduction of the amounts of epididymal secretions (eg alpha-glucosidase, L-carnitine) or immunological interference with secreted proteins (eg D/E, P34H, P26h) than by direct actions of drugs on sperm function (eg inhibition of glyceraldehyde 3-phosphate dehydrogenase by chloro-compounds). The latter approach holds promise for mankind as human sperm are susceptible to glycolytic inhibition. Future contraceptive developments may arise from production of targeted inhibitors, research on the displacement of sperm proteins in the epididymis and interference with sperm plasma membrane ion channels.
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PMID:Approaches to post-testicular contraception. 1122 1

The authors carried out a retrospective study of 162 cases of male infertility explored in a hospital unit in Lyon, France. Assays of 1 -alpha-1,4-glucosidase (epididymal function marker) backed up by clinical findings were used to select 3 types of epididymal malfunction. 1) There was complete obliteration of the epididymal duct, resulting in azoospermia. This diagnosis was based on both testicular biopsy findings, demonstrating unimpaired spermatogenesis and on the dramatically reduced level of assayed activity ( 40 mIU/ejaculation), as well as on clinical findings. 2) There was anamalous epididymal function combined with moderate oligoasthenozoospermia or normospermia. In these cases, low levels of assayed activity do not parallel fairly high sperm counts (between 20-30 million spermatozoal/ml). 3) There were those cases which were difficult to interpret and which involved severe oligoasthenozoospermia ( 5 million/ml) and reduced level of epididymal marker, suggesting partial blockage of the epididymis due to a focus of infection. Varicoceles were found more frequently among the European population, whereas a history of genital infection was more frequent among the North African population. However, when the various types of abnormality in the spermatogram were related to patient history and epididymal abnormality, no differences were found between the 2 populations. (author's modified)
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PMID:[Comparative study of epididymal disorders in two populations of male patients consulting for infertility: one from the Maghreb region of North Africa and the other of European origin]. 1231 60

The present study was designed to determine the response of human epididymis, seminal vesicles and prostate function after a 5-day course of clomiphene citrate in men attending an infertility service. In 45 men, the secretions of the epididymis, seminal vesicles and prostate were assessed by measurements of seminal alpha-glucosidase, fructose and acid phosphatase, respectively. Subjects were classified as normal or abnormal: abnormal men were defined as those who either had history of a sexually transmitted disease (STD), leukocytospermia, hypoandrogenism, or a low response of Leydig cells to clomiphene stimulation; and normal subjects were those who did not have these conditions. Mean serum testosterone luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were significantly increased after the short course with clomiphene citrate. After clomiphene citrate stimulation, the men in the normal group showed significantly increased marker levels of the seminal vesicles (P < 0.02) and prostate (P < 0.05), but not of the epididymis (P : NS). Men classified as abnormal showed no response according to the markers of the seminal vesicles and epididymis. Men with history of STD and abnormal basal values of acid phosphatase did not respond to the treatment. Men with history of STD but normal basal values of seminal acid phosphatase increased significantly in their levels of seminal acid phosphatase after clomiphene stimulation (P < 0.02). Multivariate analysis showed that the basal serum testosterone level was the only variable in predicting the probability of response to the clomiphene in terms of true-corrected seminal fructose, seminal acid phosphatase and seminal alpha-glucosidase levels. In fact, a high response of the seminal vesicles was observed in men with the highest basal serum testosterone levels (0.45 +/- 0.17; coefficient of regression +/- standard error; P < 0.018). However, a high response in terms of seminal acid phosphatase (P < 0.004) or alpha-glucosidase (P < 0.037) was observed in men with low basal serum testosterone levels. In conclusion, in the normal men, true-corrected fructose and acid phosphatase but not alpha-glucosidase in semen increased after duplicate androgen stimulation. An absence of response was observed in cases with history of STD/leukocytospermia or hypoandrogenism.
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PMID:Basal serum testosterone as an indicator of response to clomiphene treatment in human epididymis, seminal vesicles and prostate. 1239 89

Chloroform extracts of the bark of Quassia amara in different dilutions was used to assess its impact on the male reproductive system of albino rats. Single daily intramuscular injections of the extract for 15 days resulted in a significant reduction in the weight of testis and epididymis but not that of the seminal vesicles and prostate (all lobes). A marked decrease in the sperm count, motility, viability was also observed in sperm collected from the cauda epididymis of treated animals. A number of abnormalities like double heads, double tails, detached heads and fragile tails were frequently seen. Epididymal alpha-glucosidase activity was drastically reduced. However, prostatic acid phosphatase activity and citric acid levels and seminal vesicle fructose concentrations remained unchanged following treatment. Thus, it appears that the prime site of action is at the level of both the testis and the epididymis. Examination of the blood showed that cell counts and hemoglobin levels were in the normal range. Bilirubin, SGPT, SGOT, protein and urea were also not altered by the herbal extract. From the selective action on the male reproductive tract we suggest that the chloroform extract of the bark of Quassia amara has potential for use as an antifertility agent.
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PMID:A comprehensive evaluation of the reproductive toxicity of Quassia amara in male rats. 1250 57

Following the intravasal injection of a new male contraceptive RISUG (reversible inhibition of sperm under guidance) in volunteers, routine semen analysis, semen biochemistry and germ cell morphology were evaluated in comparison with the corresponding preinjection samples for a maximum period of 6 months. Sperm counts in all 25 subjects before injection varied from 45 to 120 x 10(6)/ml. Out of 25 subjects, 6 became azoospermic after 1 month, 15 after 2 months, 3 after 3 months and 1 after 4 months of contraceptive injection. The mean volume of the ejaculates was found to be less as compared to preinjection samples. Occasional sperm or sperm heads and immature germ cells were identified in only a few postinjected subjects. However, no pregnancy was reported in these subjects during the study period. Abnormal morphology found in most of the sperm, but not in the accompanying immature germ cells, may be due to a charge-related effect on the former but not on the latter cells. Neutral alpha-glucosidase, the biochemical marker for epididymis, was estimated to be significantly lower in the seminal plasma of all the postinjected subjects. On the other hand, acid phosphatase activity and fructose levels in the seminal plasma were found to be in the normal range. Based on the above findings, it is concluded that at least for the present study period, RISUG, a new male contraceptive, is effective as a partially occluding agent in the vas deferens.
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PMID:A short-term evaluation of semen and accessory sex gland function in phase III trial subjects receiving intravasal contraceptive RISUG. 1252 62


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