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)

Gossypol administered orally to male rats at a daily dose of 20 mg/kg body weight for 63 days caused hypertrophy of the cauda epididymal epithelium, with more than fourfold increase in height of the cells. The principal cells lost most of their microvilli and formed apical blebs which appeared to produce the dense secretory material which was found in the lumen. Less dramatic but similar changes also occurred after 9 days on the same regimen, with the height of the epithelium doubling. However after 19 days on this regimen, with the height of the epithelium doubling. However after 19 days on this regimen, the epithelium looked fairly normal apart from a maintained hypertrophy. As reported in other studies, the cauda epididymal sperm were severely damaged and immotile; many were decapitated and the oxygen uptake was low. Ultrastructural defects were abnormal or absent mitochondria, absence of plasma membranes and axonemal components and accessory fibres.
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PMID:Electron microscopic observations on the effect of gossypol on rat cauda epididymis. 222 26

This study was undertaken with a view to investigate the possible mechanism(s) of antifertility action of gossypol acetate in rats and hamsters. Adult male rats were treated by gavage with 30 mg/kg/day of gossypol for 7 weeks and adult male hamsters were treated similarly with 20 mg/kg/day gossypol for 8 weeks. The treatment caused a marked reduction in the weights of testis and epididymis. Histological examination of the testis in the two species revealed presence of seminiferous tubules showing varying degrees of damage along with a large number of normal tubules. Exfoliation of germ cells and spermatogenic arrest at spermatid stage was a common feature. Leydig cells presented normal morphological features. Though there was a reduction in the diameter of epididymal tubules, the epithelium did not show any morphological alterations. Examination of vasal flushings revealed marked reduction in sperm population and consisted of decapitated and immotile spermatozoa. Gossypol caused a significant reduction in the levels of total protein, RNA and DNA, and a marginal decrease in glycogen content in the testis. This was accompanied by a reduction in the activities of SDH and MDH. Except for LDH activity which showed a marked rise, there was no effect on glycolytic enzymes in the testis. The concentrations of glycerylphosphorylcholine and sialic acid were reduced in the cauda epididymis. The antifertility effects of gossypol appear to be due to its action both on testis as well as on epididymis.
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PMID:Studies on mechanism(s) of antifertility action of gossypol in rat and hamster. 246 50

Gossypol acetic acid (20, 25 or 30 mg/kg/day orally for 5 weeks) decreased epididymal weight in adult Sprague-Dawley rats but the epididymal concentrations of proteins, lactate dehydrogenase and acid phosphatase were unchanged. The concentrations of carnitine, inositol and potassium in epididymal fluid were decreased in a dose-related manner. These modifications were not due to disturbances of Leydig and Sertoli cell functions which were normal. We suggest that the reduction in epididymal secretion results from a decrease in the number of spermatozoa rather than from a direct action of gossypol on the epididymal epithelium.
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PMID:Gossypol-induced modifications in the microenvironment of rat epididymal spermatozoa. 276 Aug 73

Gossypol administered orally to male rats at a daily dose of 20 mg/kg body weight for 62 days caused infertility. There were changes in the epididymal epithelium and the sperm were severely damaged and immotile. The sperm head was often detached; other defects were abnormal mitochondria, absence of plasma membranes and axonemal and accessory fibres and a lower oxygen uptake. To study the effect of gossypol on the motor apparatus of sperm, ram sperm were demembranated with the detergent, Triton-X-100. Such sperm models can normally be reactivated with ATP but gossypol (2.5-12.5 microM) decreased reactivation and must have a direct effect on the axoneme. Gossypol also inhibited ram sperm adenyl cyclase which is essential for maintaining high levels of cAMP in sperm and, in turn, motility. Ram sperm adenyl cyclase required Mn2+ for activity and high Mn2+ concentrations protected the enzyme from gossypol inhibition. Electron spin resonance studies proved that gossypol chelated Mn2+ with the formation of a 2:1 complex.
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PMID:Studies of the mechanism of action of gossypol as a male antifertility agent. 283 27

Guinea pig spermatozoa were found to contain a fully-latent cysteine proteinase that could be unmasked by incubating epididymal sperm for 2 hr at pH 3.5 and 37 degrees C. The proteinase was identified as cathepsin L (EC 3.4.22.15) on the basis of its optimal hydrolysis of benzyloxycarbonyl-Phe-Arg-7-(4-methyl)coumarylamide (Z-Phe-Arg-NMec) at pH 5.5; lack of action on Z-Arg-Arg-NMec and Arg-NMec; urea-enhanced digestion of azocasein; marked sensitivity to thiol reagents, leupeptin, Z-Phe-Phe-CHN2, and L-trans-epoxy-succinylleucylamido(3-methyl)butane (Ep-475 or E-64-c); and insensitivity to pepstatin and serine proteinase inhibitors. Gossypol, a male antifertility agent, was inhibitory. The unmasking phenomenon was reversibly inhibited by HgCl2 and mersalyl acid, and prevented by leupeptin and Ep-475, but not by pepstatin.
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PMID:Cathepsin L--a latent proteinase in guinea pig sperm. 334 13

Gossypol acetic acid could induce total infertility in male Wistar/NIN strain rats at a dose of 30 mg per kg body weight per day, for 52 days. 20 mg for 52 days and 30 mg for 38 days produced partial infertility. Highly significant correlation between parameters of infertility like reduced cauda sperm count, and implantation sites, and reduction in LDH-X activity of cauda epididymal sperm and carnitine levels in cauda epididymal fluid were observed. Testis remained unaffected.
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PMID:Dose and time related changes in LDH-X activity, epididymal carnitine levels and fertility, in gossypol-treated male rats. 356 62

The present investigations were carried out to show the histological and ultrastructural alterations in rat testes 10 weeks after gossypol acetic acid treatment (dose: 30 mg gossypol acetic acid/kg/day). the morphological findings in the interstitial compartment were compared with the data from studies carried out to investigate the testosterone biosynthesis in gossypol acetic acid treated rats. No morphological changes in the epididymal and vasal epithelia were found; however, the germinal epithelial cells showed vacuolisation, pycnosis, disconnections of junctions, cytolysis and exfoliation of germ cells from the epithelium. The Sertoli cells were affected, too. Gossypol acetic acid seemed to stimulate the physiological activity pathologically; cellular organelles as mitochondria, endoplasmic reticulum, lysosomal vacuoles, pigment granules and nuclei were either enlarged in size and number or malformed in shape. The cellular contact was often restricted to spots or completely disconnected. If gossypol acetic acid was administered for a longer period of time some Sertoli cells were found to be unable to withstand the toxic stimulus, and the cells became necrotic too. In contrast to the toxic process in the germinal and Sertoli cells the Leydig cell compartment did not show any changes in fine structure, and therefore testosterone biosynthesis is presumed to be intact.
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PMID:Ultrastructural analysis of rat testes after gossypol acetic acid (GAA) treatment. 686 21

Reversible male antifertility activity was obtained with orally administered gossypol acetic acid in rats at 20 mg/kg/day and in hamsters at 10 mg/kg/day but not in mice at dosages up to 40 mg/kg/day. An increased number of degenerating spermatocytes was found in the testicular tubular lumens of rats. Pigment-laden cells containing an intracytoplasmic lipofuscin-like material were noted in the testis and epididymal interstitium in rats and mice. Gossypol was also tested in the female for effects on ovulation and pregnancy. Gossypol did not inhibit ovulation in the rat at dosages up to 80 mg/kg/day but did cause 90% inhibition of pregnancy in mice treated with 80 mg/kg/day during the first two weeks of pregnancy. In several standard endocrine bioassays, gossypol did not demonstrate estrogenic, antiestrogenic, androgenic or antiandrogenic activities, but it did potentiate the androgenicity of methyltestosterone.
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PMID:Antifertility and endocrine activities of gossypol in rodents. 727 69

The ability of intact cells to reduce spin labels has been utilized to characterize the activity of spermatozoa of goat. The kinetics of reduction of TEMPO has been found to be sensitive to the quantity, quality and state of epididymal maturation of the spermatozoa. Presence of alcohol caused activation and Gossypol acetic acid left sperm activity unaltered. Electron spin resonance (ESR) and 31P Nuclear magnetic resonance (NMR) indicate that the period of in vitro capacitation requires optimization. 31P NMR spectra indicate a good correlation with the progressive maturation of the cells.
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PMID:Maturation, capacitation, and metabolism of goat spermatozoa using magnetic resonance methods. 839 62

Gossypol, a polyphenolic aldehyde naturally present in cottonseed, has long been recognized as a male contraceptive and recently as a potential anticancer agent. Our study used a rodent model to evaluate gossypol's potential for the treatment of human prostatic carcinoma. Two-month-old Copenhagen male rats received subcutaneous implants of a subpassage of MAT-LyLu prostatic cancer line, a highly metastatic, androgen-independent Dunning prostate tumor subline that specifically metastasizes to lymph nodes and lungs of recipients. After 2 weeks of gossypol treatment (0 or 12.5 mg/kg B.W./day S.C.) initiated immediately after transplantation, the rats were sacrificed and evaluated for prostate tumor growth and metastasis. Testosterone and gossypol levels in tumor tissue and various reproductive organs and serum potassium level were measured by radioimmunoassay (RIA), high pressure liquid chromatography (HPLC) and atomic emission spectroscopy (AES), respectively. Gossypol-treated rats exhibited weight reductions in developed MAT-LyLu prostate tumor mass and prostate of 24% (p < 0.05) and 31% (p < 0.05), respectively; whereas testicular and epididymal weights were not significantly affected. Few metastases (20%) were observed in either lymph nodes or lungs of gossypol-treated recipients. The control rats, however, had a much higher rate of lung (60%) and lymph node metastasis (40%). Testicular testosterone levels, as measured by RIA, were significantly lower in gossypol-treated rats than in controls (p < 0.05), but serum testosterone levels were not different. Extractable gossypol content in the prostate tumor, as measured by HPLC, reached 19.67 ng/gm and was 1.28 times higher than in liver, 1.98 times higher than in testes, but was 3.3% of that in prostate. Moreover, serum had the highest gossypol content (10.7 micrograms/ml). Serum potassium levels, as measured by AES, were significantly higher in gossypol-treated individuals than controls (p < 0.05). Our results indicate for the first time that gossypol has antiproliferative and antimetastatic effects on MAT-LyLu prostate cancer cells and can be explored as a potential therapeutic agent for androgen-independent human prostatic carcinoma.
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PMID:Antiproliferative and antimetastatic effects of gossypol on Dunning prostate cell-bearing Copenhagen rats. 848 76


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