Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of androgen withdrawal and replacement on the concentrations of androgen receptor (AR) protein and AR mRNA were investigated in rat ventral prostate and seminal vesicles and in cultured human hepatoma (HepG2) cells. AR mRNA concentrations were determined by Northern blotting with single stranded AR cRNA as the hybridization probe, whereas antibodies raised against two synthetic 17-amino acid long peptides corresponding to the N-terminal and steroid-binding regions of the AR were employed in immunological receptor assays. AR mRNA levels in both prostate and seminal vesicles increased about 2-fold within 24 h after castration and continued to rise within the next 48 h to values that were 9- to 11-fold higher than those in intact controls. Administration of pharmacological doses of testosterone (400 micrograms steroid/day) to 1-day castrated animals for 24-48 h brought about a decrease in AR mRNA levels in accessory sex organs to levels in intact controls. Similar results were obtained in cultured HepG2 cells where a switch to serum- and steroid-free medium elicited a rapid increase (approximately 4-fold in 10 h) in the AR mRNA level, which was prevented by inclusion of 10(-7) M testosterone in culture medium. Similar, but quantitatively less marked, changes occurred in the AR protein concentration in prostate, seminal vesicles, and HepG2 cells, as determined by immunoblotting using antibodies against AR peptides. In addition, immunohistochemical studies showed that AR is a nuclear protein of the prostatic epithelial cells in both intact and castrated rats, and suggested that short term castration increases the concentration of nuclear AR in the prostate. Taken together, these data indicate that androgens down-regulate the concentration of AR protein and AR mRNA in a variety of target tissues.
Mol Endocrinol 1990 Nov
PMID:Regulation of androgen receptor protein and mRNA concentrations by androgens in rat ventral prostate and seminal vesicles and in human hepatoma cells. 217 37

We have used monoclonal antibodies against the estrogen (E), progestin (P) and androgen (A) receptors (R) to study receptor localization and regulation in the seminal vesicles of rhesus monkeys under different hormonal conditions. The antibodies caused substantial shifts of the appropriately labeled receptors on sucrose gradients. ER levels were lower in intact males than in immature, castrate, and estrogen-treated castrates. With immunocytochemistry, ER were detectable only in stromal and smooth muscle cells, not the epithelium. The number of ER-positive stromal cells was significantly lower in intact males than in immature, castrate, and estrogen-treated castrates, and low in a DHT-treated castrate animal. Androgen receptors were localized in epithelial as well as stromal and smooth muscle cells, and the number of AR-positive stromal cells was highest in intact adults and lowest in castrated and immature animals. Estrogen treatment at the time of castration induced PR in the ER-positive stromal cells, prevented a decline in the number of AR-positive stromal cells, and caused stromal hypertrophy. In summary, in the seminal vesicle, as in the prostate, ER is restricted to the fibromuscular stroma, is suppressed by androgens, and can mediate induction of PR on estrogen treatment. Androgen receptors are present in epithelial as well as stromal and smooth muscle cells, but variations in hormonal state appear to affect regulation of AR more in the stroma than the epithelium.
J Steroid Biochem Mol Biol 1990 Sep
PMID:Localization and regulation of estrogen, progestin and androgen receptors in the seminal vesicle of the rhesus monkey. 224 43

Heparin binds to bovine sperm and stimulates capacitation in vitro. Seminal plasma alters the ability of epididymal sperm to bind heparin, and several heparin-binding proteins (HBPs) have been identified in bull seminal plasma. This study had three objectives: 1) to identify production sites of seminal plasma HBPs, 2) to determine which HBPs bound to cauda epididymal sperm, and 3) to determine whether presence of HBPs was testosterone dependent. Proteins from bull or rat seminal vesicles, prostates, and bulbourethral glands were separated by heparin affinity high-performance liquid chromatography. HBPs were found in all accessory glands of rats and bulls, but the major source of bovine seminal plasma HBPs appeared to be seminal vesicles. Between 25% and 50% of the protein from each gland bound to the heparin column, and NaCl concentrations required to elute proteins ranged from 0.15 to 1.4 M. One-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that major HBPs were relatively small, with molecular weights between 13 and 31 kDa, but some HBPs also exhibited higher molecular weights, between 40 and 100 kDa. Radioiodinated HBPs from each bovine gland were incubated with epididymal sperm. Labeled HBPs binding to sperm exhibited molecular weights of 14, 16, 24, and 30 kDa as determined by SDS-PAGE and autoradiography. The HBP content of the accessory sex glands decreased significantly in castrated rats and was restored to levels of sham-operated controls by testosterone replacement. Heparin-binding proteins may play a role in fertilization by attaching to sperm surfaces, enabling heparin-like glycosaminoglycans in the female reproductive tract to induce capacitation.
Mol Reprod Dev 1990 Mar
PMID:Male accessory sex glands produce heparin-binding proteins that bind to cauda epididymal spermatozoa and are testosterone dependent. 233 73

The fertilization antigen (FA-1) isolated from murine testes demonstrated its dimeric form of 49,000 +/- 2,000 molecular weight (M.W.) or a monomer of 23,000 M.W. on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The FA-1 was immunogenic in all three female rabbits tested and raised a high-titer antisera [enzyme-linked immunosorbent assay (ELISA) titers; 1:1,024 to 1:4,096]. The rabbit anti-FA-1 antisera predominantly recognized the dimeric form of 49,000 +/- 2,000 M.W. on the Western blot of lithium diiodosalicylate (LIS)-solubilized murine testes. None of the antisera reacted with any somatic tissue, indicating germ-cell specificity of FA-1. To determine the cellular localization of the immunoreactive FA-1, a novel ultrasensitive immunogold-silver staining (IGSS) procedure was developed. The anti-FA-1-IgG showed intense staining in the luminal region of the seminiferous tubules containing spermatids and spermatozoa. No reaction was observed in the peripheral area of the tubules containing Sertoli cells, spermatogonia, leptotene, and zygotene spermatocytes. The biodistribution studies of 125I-labeled anti-FA-1 IgG in mice revealed that the antibodies do not bind to somatic tissues such as blood cell, liver, heart, kidney, muscle, and gastrointestinal tissue and do not transudate into testes and seminal vesicle. However, the antibodies preferentially transudate into epididymis (especially corpus or cauda regions) and vas deferens to bind to sperm cells. In conclusion, our data indicate that FA-1 can induce an immune response that is germ cell-specific, directed against later stages of spermatogenesis. The antibodies to FA-1 interact with sperm after penetration through epididymis (especially corpus and cauda regions) and vas deferens rather than through testes and seminal vesicles.
Mol Reprod Dev 1990 Jun
PMID:Antibodies to sperm surface fertilization antigen (FA-1): their specificities and site of interaction with sperm in male genital tract. 237 99

Histopathological changes induced by immune responses generated against luteinizing hormone releasing hormone (LHRH) were studied in adult male Wistar rats. Active immunization with a semisynthetic anti-LHRH vaccine, LHRH D-Lys6, (10, 40, and 80 micrograms/animal) conjugated with diphtheria toxoid, produced bioeffective antibodies as indicated by significant reduction in circulating testosterone levels. At the 14th week after immunization the animals were sacrificed and reproductive organs were evaluated. These organs were studied for histopathological changes and compared with those of nonimmunized control rats. Marked hypoplastic changes were observed in the genital organs. Testicular changes such as arrest of spermatogenesis at the spermatocyte level and atrophic changes in the interstitial Leydig cells were noticed in treated animals. Similarly attenuation of secretory epithelial cells with substantial increase in the stromal tissues was observed in the prostate and seminal vesicles. The current observation suggests the possible usefulness of this anti-LHRH vaccine under clinical conditions where reduction in androgenic response is desired as in the case of hormone-dependent prostatic carcinoma.
Exp Mol Pathol 1990 Feb
PMID:Histopathological changes in reproductive organs of male Wistar rats following active immunization against LHRH. 240 46

All the major androgen-regulated secretory proteins of rat seminal vesicles have been purified in high yield from polyacrylamide gels using electroelution. In the process a sixth previously undocumented protein has been identified. Amino acid compositions of all the proteins are very similar and highly unusual, being high in lysine and arginine, and with 40-50% of the residues accounted for by serine, glycine and glutamate/glutamine. N-Terminal amino acid sequences for 3 of the proteins show that they are clearly the products of related genes. At least one of the other proteins is N-terminally blocked in vivo. Antibodies specific for each protein have been raised and provide evidence of structural similarity between the proteins. The antibodies were also used in immunofluorescence histochemistry with the rat copulatory plug, showing for the first time that all the major proteins of seminal vesicle secretion are components of this reproductive structure.
Mol Cell Endocrinol 1986 May
PMID:Androgen-regulated proteins of rat seminal vesicle secretion constitute a structurally related family present in the copulatory plug. 242 95

Certain toxic effects of phenytoin are thought to result from its cytochrome P-450-catalyzed bioactivation to a reactive arene oxide intermediate that binds covalently to proteins. Using an in vitro system, we examined an alternative hypothesis based upon the cooxidation of phenytoin to a reactive free radical intermediate by prostaglandin synthetase (PGS), horseradish peroxidase, or thyroid peroxidase. Microsomes from hepatic, thyroid, seminal vesicular, or pulmonary tissues, or PGS or horseradish peroxidase, were incubated with the appropriate enzymatic cofactors to study activities of cytochromes P-450 (NADPH), PGS (arachidonic acid), thyroid peroxidase (guiaicol, H2O2), and horseradish peroxidase (H2O2). The production of potentially teratogenic, reactive phenytoin intermediates during in vitro incubations was estimated by the amount of radiolabeled phenytoin bound covalently to microsomal protein or bovine serum albumin and by the detection of a free radical intermediate using ESR spectrometry. Arachidonic acid-dependent bioactivation of phenytoin was demonstrated for purified PGS and ram seminal vesicles (RSV), as well as for liver, lung, and kidney. Optimal arachidonate concentrations varied substantially for different tissues. Arachidonate-dependent binding of phenytoin with PGS and RSV was reduced to baseline levels by coincubation with the cyclooxygenase inhibitor indomethacin. Hydrogen peroxide-dependent covalent binding of phenytoin was observed with thyroid peroxidase and horseradish peroxidase, and binding was significantly reduced in these systems and in PGS and RSV by coincubation with the peroxidase inhibitor methimazole. Glutathione, the antioxidants caffeic acid and butylated hydroxyanisole, and the free radical trapping agent alpha-phenyl-N-t-butylnitrone (PBN) all significantly reduced arachidonate-dependent phenytoin binding. Oxygen uptake was increased in a dose-dependent manner by the arachidonate-dependent bioactivation of phenytoin by PGS. ESR spin-trapping techniques using PBN indicated the generation of a free radical intermediate during the metabolism of phenytoin by PGS. These results suggest that the hydroperoxidase component of PGS, as well as thyroid peroxidase and other peroxidases, can bioactivate phenytoin to a reactive free radical intermediate, which may be toxicologically relevant.
Mol Pharmacol 1989 Apr
PMID:In vitro bioactivation of phenytoin to a reactive free radical intermediate by prostaglandin synthetase, horseradish peroxidase, and thyroid peroxidase. 253 58

We evaluated transcript levels for the rate-limiting enzyme in polyamine biosynthesis, ornithine decarboxylase (ODC), in rat tissues by Northern blotting and in situ hybridization histochemistry, using a rat cDNA probe. ODC transcripts were expressed at a high level, relative to levels in other tissues, in the kidney and testis of the adult rat; maximal levels of transcripts in these tissues occurred after sexual maturation had taken place, i.e. between 20 and 150 days of age. In situ hybridization histochemistry revealed high level expression in the kidney, testis, prostate, and seminal vesicles of the male rat; this high level expression was limited to certain cell types: kidney, S3 cells of the proximal convoluted tubule; prostate and seminal vesicles, glandular or luminal epithelial cells; and testis, early spermatogenic cells. High level expression of ODC mRNA disappeared from the prostate and seminal vesicle epithelial cells after castration and reappeared with testosterone treatment; in contrast, levels of kidney ODC mRNA were essentially unchanged by castration and were similar in male and female adult rats. We conclude that high level ODC mRNA expression occurs in specific cell types in the adult rat, where it appears to be regulated by both androgen-dependent and independent mechanisms.
Mol Endocrinol 1989 Jan
PMID:High level, cell-specific expression of ornithine decarboxylase transcripts in rat genitourinary tissues. 291 49

Follicular prostaglandins (PG) increase markedly in the hours after the preovulatory gonadotropin rise in the rat. The present investigation was performed to determine if the increased prostaglandins result from elevation of the amount of the principal enzyme in the conversion of arachidonic acid to prostaglandins, i.e. PG synthase. PG synthase was purified from sheep seminal vesicles and rat ovaries for the preparation of monoclonal antibodies. A monoclonal antibody was utilized in a competitive, microtiter plate-based enzyme immunoassay to quantitate PG synthase protein. Follicular development was stimulated in 26-day-old rats by injection of 20 IU of PMSG, and 51 h later 20 IU of hCG was injected. Ovaries were removed from rats before and 8 h after the hCG injection for quantitation of PG synthase by enzyme immunoassay. PG synthase immunologic activity was increased three-fold by hCG stimulation. These findings support the hypothesis that the preovulatory gonadotropin rise causes increased PG synthase protein in the rat ovary.
Mol Cell Endocrinol 1987 Apr
PMID:Human chorionic gonadotropin stimulation of immunoreactive prostaglandin synthase in the rat ovary. 310 18

Prostaglandin-H-synthase (PHS) peroxidase has been suggested to mediate drug metabolism particularly in extrahepatic tissues low in monooxygenase (MFO) activity. PHS can oxidize various xenobiotics in vitro; its contribution in vivo is still uncertain and is currently assessed by differences in the MFO- and PHS-catalyzed product/adduct formation of a few suitable substrates. Cells in culture that are PHS competent but MFO deficient can provide an additional approach for further investigating the role of PHS in the metabolic activation of foreign compounds. To this end, a cell line has been derived from ram seminal vesicles (SEMV), a tissue known as a good source of PHS but shown to be devoid of MFO activity. SEMV cells can be cultured in IBR or in RPMI medium supplemented with fetal calf serum, and have been subcultured until passage 30. The arachidonic acid (AA) metabolism in these cells has been characterized: besides incorporation in the lipid pool, AA was mainly metabolized to prostaglandin (PG) E2; minor products were PGF2 alpha and the lipoxygenase products 12- and 15-HETE. The PGE2 production (17 nmol/10(6) cells.24 h) of SEMV cells (passage 10) exceeded at least 10-fold that of other cells cultured under similar conditions. These data, indicative of high PHS activity, suggest that the cells can be a useful tool for future studies on the objectives outlined above.
Mol Toxicol
PMID:Prostaglandin-H-synthase competent cells derived from ram seminal vesicles: a tool for studying cooxidation of xenobiotics. 315 3


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