Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of acrosin (AC), hyaluronidase (HY), tubulin (TU), dynein (DY), and actin (ACT) has been examined by indirect immunofluorescent measurement in sperm preparations from infertile patients to investigate the sperm fertilizing ability. The fluorescence scores were determined by the chromatically positive rates of each antibodies. In cases in which semen showed lower concentration (oligozoospermia and oligoasthenozoospermia), the scores of these proteins were all significantly lower than those of normozoospermia. In cases in which semen showed lower motility (asthenozoospermia and oligoasthenozoospermia), the scores of AC, HY, TU, and ACT were significantly less. In semen that contained numerous morphologically abnormal spermatozoa, TU and ACT exhibited a significant reduction. These results indicate that sperm productibility may be involved in all proteins and that less-motile and morphologically abnormal spermatozoa are involved in structural or functional disorder of the proteins constituting the tail. The normality of these fluorescence scores showed a good correlation with pregnancy rate, but semen analysis did not show any correlation with pregnancy rate. It would appear that this immunofluorescent procedure has an advantage over semen analysis and yields useful information on sperm fertilizing ability.
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PMID:Correlation of semen characteristics with acrosin, hyaluronidase, tubulin, dynein, and actin of spermatozoa. 858 72

Cysteamine (beta-mercaptoethylamine, or MEA) is a thiol-reducing agent and has anti-HIV activity. Because of these properties, cysteamine was evaluated as a vaginal contraceptive and tested for its effects on sperm function and on other sexually transmitted microbes. Cysteamine was contraceptive in the rabbit. Conception was inhibited completely when sperm were pretreated with 500 microg/ml cysteamine and was inhibited by more than 60% when 7.5 mg cysteamine was applied vaginally as a suspension in 50% K-Y Jelly. Cysteamine had multiple effects on spermatozoa. Both acrosin (EC 3.4.21.10) and hyaluronidase (EC 3.2.1.35) were reversibly inhibited by cysteamine. Calculated IC50 values were 370 microg/ml and 150 microg/ml for acrosin and hyaluronidase, respectively. Cysteamine behaved as a poor spermicide when activity was measured by the 30-second Sander-Cramer test. However, sperm motility was inhibited completely when cysteamine was preincubated for 10 minutes prior to motility evaluation, at concentrations as low as 50 microg/ml. The calcium ionophore A23187-induced human acrosome reaction was inhibited by cysteamine (IC50 = 0.5 microg/ml). Neither herpes simplex virus nor Neisseria gonorrhoeae was affected by cysteamine at concentrations as high as 500 microg/ml and 100 microg/ml, respectively. Cysteamine appears to have no effect on normal vaginal flora (i.e., lactobacillus). These results, together with published data, strongly support the further development of cysteamine as a topical contraceptive anti-HIV agent.
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PMID:Characterization of cysteamine as a potential contraceptive anti-HIV agent. 953 90

Effects of a combination of medoxy-progesterone acetate (MPA) and dihydrotestosterone (DHT) at a dose of 10 mg + 2 mg/kg, injected, in weekly to rats of proven fertility were investigated with respect to their fertility, sperm and organ functions. This hormonal regimen had no effect in body and organ weights except in the testis. A depletion in sperm reserves in testis and epididymis was noted in addition to a loss of their motility in the later. Alterations in cauda epididymal sperm viability and morphology and reduced levels of superoxide dismutase indicated changes in their plasma membrane permeability. Sperm acrosomal enzymes such as acrosin and hyaluronidase were also affected leading to a loss of their function. Consequently the fertility potential of these rats also impaired after 60 days of hormonal regimen. Testicular biochemical machinery revealed its altered metabolism and regressed spermatogenic activity accounting for its loss of weight. Similarly epididymal physiology also exhibited changes leading to impaired sperm maturation. However, toxicity studies showed no significant variations in liver and blood biochemical profiles indicating non-toxic nature of this combination. All these effects seemed to be transient and reversible upon withdrawal of treatment for 60 and 90 days gradually. Thus, this combination with aromatizable androgen is useful for induction of functional sterility.
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PMID:Endocrine approach to male fertility control by steroid hormone combination in rat Rattus norvegicus L. 983 78

A commercial preparation of a sodium polystyrene sulfonate (designated as N-PSS; its molecular weight is 500000 daltons) was tested as an inhibitor of sperm function and as a preventive agent for conception and the transmission of sexually transmitted diseases. The polymer is an irreversible inhibitor of hyaluronidase and acrosin; its IC50 values are 5.7 microg/mL and 0.5 microg/mL, for hyaluronidase and acrosin, respectively. N-PSS is also a stimulus of human sperm acrosomal loss. It produces maximal acrosomal loss at 2.5 microg/mL. Contraception in rabbits is nearly complete when rabbit spermatozoa are pretreated with 0.5 mg/mL of N-PSS before artificial insemination; however, N-PSS does not immobilize spermatozoa at concentrations as high as 50 mg/mL. N-PSS has broad spectrum antiviral and antibacterial activities. Infection by human immunodeficiency virus and herpes simplex virus are inhibited by N-PSS; 3-log reductions are produced by 7 microg/mL and 3 microg/mL, respectively. N-PSS is active against Chlamydia trachomatis and Neisseria gonorrhoeae. At 1 mg/mL, N-PSS inhibits chlamydial infectivity by more than 90%. N-PSS produces a 3-log reduction in gonococcal growth at 15 microg/mL. In contrast, N-PSS (5 mg/mL) does not affect the growth of Lactobacillus (normal component of the vaginal flora). N-PSS can be classified as a noncytotoxic contraceptive antimicrobial agent. These properties justify bringing a polystyrene sulfonate into clinical trials for its evaluation as a preventive agent for conception and several sexually transmitted diseases.
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PMID:Evaluation of poly(styrene-4-sulfonate) as a preventive agent for conception and sexually transmitted diseases. 1110 13

To elucidate the mechanism of sterility induced by gossypol, we studied the relationship between the activities of acrosomal enzymes and their fertilizing capacity in the hamster. The results showed that the ability of spermatozoa to penetrate into bovine cervical mucus, hyperactivated motility (HAM) and fertility in vivo were significantly inhibited when spermatozoa were exposed to gossypol (2.5 microg - 60 microg/mL) for 15 min in vitro. Also, following administration of gossypol (12.5 mg/kg/day) for 6 weeks, sperm motility, HAM and rate of fertilization in vitro by the hamster cauda epididymal spermatozoa were significantly decreased and the extracts of testis delayed dispersion of the cumulus oophorus cells, suggesting that hyaluronidase and other acrosomal enzymes might be inhibited by gossypol. In addition, acrosin and arylsulfatase activities were also markedly inhibited. These data show that the inhibition of acrosin and arylsulfatase activities is the main cause of gossypol-induced infertility. The inhibition was dependent upon gossypol dose and the duration of administration. Thus, the assay of acrosin and arylsulfatase activities may provide a useful tool for monitoring sterility induced by gossypol.
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PMID:Inhibition of hamster sperm acrosomal enzyme by gossypol is closely associated with the decrease in fertilization capacity. 1113 75

Host cell infection by sexually transmitted disease (STD)-causing microbes and fertilization by spermatozoa may have some mechanisms in common. If so, certain noncytotoxic agents could inhibit the functional activity of both organisms. High molecular mass poly(sodium 4-styrenesulfonate) (T-PSS) may be one of these compounds. T-PSS alone (1 mg/ml) or in a gel (2% or 5% T-PSS) completely prevented conception in the rabbit. Contraception was not due to sperm cytotoxicity or to an effect on sperm migration. However, T-PSS inhibited sperm hyaluronidase (IC(50) = 5.3 microg/ml) and acrosin (IC(50) = 0.3 microg/ml) and caused the loss of acrosomes from spermatozoa (85% maximal loss by 0.5 microg/ml). T-PSS (5% in gel) also reduced sperm penetration into bovine cervical mucus (73% inhibition by 1 mg gel/ml). T-PSS (5% in gel) inhibited human immunodeficiency virus (HIV; IC(50)= 16 microg gel/ml) and herpes simplex viruses (HSV-1 and HSV-2; IC(50) = 1.3 and 1.0 microg gel/ml, respectively). The drug showed high efficacy against a number of clinical isolates and laboratory strains. T-PSS (5% in gel) also inhibited Neisseria gonorrhea (IC(50) < 1.0 gel/ml) and Chlamydia trachomatis (IC(50) = 1.2 microg gel/ml) but had no effect on lactobacilli. These results imply that T-PSS is an effective functional inhibitor of both spermatozoa and certain STD-causing microbes. The noncytotoxic nature should make T-PSS safe for vaginal use. T-PSS was nonmutagenic in vitro and possessed an acute oral toxicity of >5 g/kg (rat). Gel with 10% T-PSS did not irritate the skin or penile mucosa (rabbit) and caused no dermal sensitization (guinea pig). Vaginal administration of the 5% T-PSS gel to the rabbit for 14 consecutive days caused no systemic toxicity and only mild (acceptable) vaginal irritation. T-PSS in gel form is worthy of clinical evaluation as a vaginal contraceptive HIV/STD preventative.
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PMID:Efficacy and safety of a new vaginal contraceptive antimicrobial formulation containing high molecular weight poly(sodium 4-styrenesulfonate). 1190 5

This review describes the research done so far on sperm enzyme inhibitors to establish their potential as contraceptives. The mode of action of hyaluronidase inhibitors is discussed, a chronological summary of studies showing the in vivo and antifertility activity of synthetic hyaluronidase is provided, present research needs are indicated, and marketed compounds able to inhibit hyaluronidase are identified. The mode of action of acrosin inhibitors, advantages and shortcomings of different acrosin-inhibiting agents and certain ions, and potential utility of acrosin inhibitors in enhancing the contraceptive potency and reducing the side effects of the IUD, and the systemic application of acrosin inhibitors to induce infertility are discussed. Possible use of gossypol as a spermicide, the effect of gossypol on the fertilizing capacity of human spermatozoa, and its possible use as a vaginal contraceptive are assessed. Theoretical and practical implications of using a form of the enzyme lactate dehydrogenase found only in the male genital tract as an antigen for contraceptive purposes are discussed. Other enzymes whose inhibitors would also lead to infertility, giving promise of contraceptive applications, are identified. The author concludes that inhibitors of sperm enzymes, whether chemical agents or antibodies, could be potent contraceptives whose use is attractive because enzymes are often sperm specific. A sperm directed contraceptive method would probably be more feasible in the female, because the concentration of the inhibitors needed to induce contraception is less and the inhibitors can be applied locally in the female. Research to date has focused on only a small number of the possible enzymes that could be inhibited to prevent fertility, primarily because too little is known about the biochemical properties of the sperm enzymes and their role in fertility.
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PMID:Sperm enzyme inhibitors for vaginal and other contraception. 1217 23

There is a growing demand for men to share the burden of responsibility and risks of contraception because of growing population pressures and the increasing dissatisfaction of women in assuming almost all the risks of adequate contraception. 3 approaches are being used in male contraceptive research: stopping sperm production, blocking sperm transport at the time of intercourse, and altering the quality or capacity of sperm to fertilize. Methods currently in use are based on physically blocking sperm from entering the female reproductive system--vasectomy, condoms, or withdrawal before ejaculation. Current research goal is the development of an effective, reversible, easily used method which neither interferes with libido nor the act of intercourse and is free of any dangerous side effects; for developing countries, added requirements are that the method must be inexpensive and easily distributed. LHRF (luteinizing hormone-releasing factor) agonists are currently being tested. The most extensive trials have involved a super agonist which is about 144 times more powerful than LHRF; however, although a 75-100% sperm reduction is possible with this method, the regime of daily injections may prove inconvenient to potential users, in addition to the unwarranted side effects (impotency, reduced libido, and 'hot flashes' or momentary increases of body temperature). Gossypol is a male pill currently being used in the People's Republic of China. Clinical trials on about 10,000 men revealed a 99.89% effectiveness and a low incidence of mild side effects. In Thailand, research is being conducted on the biochemical processes involved in sperm maturation in the hope of developing sophisticated techniques which would modify these processes and prevent conception from taking place. Another research effort aims to provide contraception precisely at the point where sperm and ovum meet using 2 enzymes (hyaluronidase and acrosin) which play a part in the penetration of sperm through the layers that surround the ovum. Another potential method is the contraceptive vaccine which would have only 1 effect--infertility. Many considerations need to be resolved before the goal of an effective, reversible, safe, and inexpensive male contraceptive is realized.
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PMID:The manly art of contraception. 1233 50

Semen samples from 12 bucks Were extended with 10 different extenders containing glycerol, DMSO, glycerol + DMSO, and glycerol + lactose in varying concentrations as cryoprotective agents. The activities of acrosin, hyaluronidase, alkaline phosphatase (AKP), aspartate aminotransferase (AST), alanine amino transferase (ALT) and lactic dehydrogenase (LDH) were assayed in equilibrated (Prefreeze) and frozen thawed (Postfreeze) semen samples. Significantly (P < 0.01) higher intracellular activity of acrosin was recorded in semen samples extended with lactose than with the other extenders, with the maximum being with Tris yolk glycerol lactose (TYGL(180)). Effects of extenders on acrosin activity were significant (P < 0.01) at both of the pre-and postfreeze stages. However, extracellular activities of hyaluronidase, alkaline phosphatase, transaminases (AST and ALT), and lactic dehydrogenase were significantly higher in extenders containing DMSO than lactose. Leakage of these enzymes was found to increase from the prefreeze to the post freeze stage.
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PMID:Effect of cryoprotectants on release of various enzymes from buck spermatozoa during freezing. 1672 4

The present study evaluated the effectiveness of ascorbic acid, catalase, chlorpromazine and their combinations in reducing the cryodamages to crossbred bull (Bos taurus x Bos indicus) spermatozoa. A total of 32 ejaculates (eight each from four bulls) were diluted in Tris-citric acid-fructose-egg yolk-glycerol extender. Each ejaculate was split into six parts (five treatment and one control). Treatment groups included 10 mm ascorbic acid, 0.1 mm chlorpromazine, 200 IU/ml catalase, 10 mm ascorbic acid + 0.1 mm chlorpromazine or 200 IU/ml catalase + 0.1 mm chlorpromazine in the extender. Fluorescent probes (Fluorescein isothiocyanate--Pisum sativum agglutinin + Propidium iodide) were used for the assessment of spermatozoa viability and acrosomal status. The proportion of acrosome intact live (AIL), acrosome intact dead, acrosome reacted live and acrosome reacted dead sperm was assessed in fresh, equilibrated and frozen-thawed semen. The functional status of the sperm was assessed using hypo-osmotic sperm swelling test (HOSST). Activities of acrosin and hyaluronidase enzyme were also determined. Lipid peroxidation level was assayed based on the melonaldehyde (MDA) production. In cryopreserved semen, the values of AIL spermatozoa, HOSST response, hyaluronidase and acrosin activity were reduced by 53%, 47%, 34% and 54%, respectively from their initial values in fresh semen. However, MDA level was threefold higher in the frozen-thawed sperm compared with fresh sperm. Significant (p < 0.05) improvement in motility, viability, HOSST response, retention of hyaluonidase and acrosin and reduction in MDA was recorded in ascorbic acid, catalase, ascorbic acid + chlorpromazine and catalase + chlorpromazine incorporated groups. The percentage of AIL sperm was significantly (p < 0.05) higher in ascorbic acid, catalase and ascorbic acid + chlorpromazine incorporated groups compared with the control. Chlorpromazine alone did not improve the post-thaw semen quality but when combined with either ascorbic acid or catalase, improvement in semen quality was noticed. It was inferred that incorporation of ascorbic acid, catalase and ascorbic acid + chlorpromazine in semen extender improved the post-thaw semen quality in crossbred bulls.
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PMID:Ascorbic acid, catalase and chlorpromazine reduce cryopreservation-induced damages to crossbred bull spermatozoa. 1903 33


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