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)

Clusterin, also known as sulphated glycoprotein-2 or testosterone-repressed prostate message-2, is a ubiquitous protein found in a variety of tissues and species. In the reproductive tract of the male rat, clusterin is regulated in a complex age-dependent and cell-specific manner. It is expressed at high levels in the epididymis and testis and at very low levels in the prostate under basal conditions. The expression of this gene in the prostate and seminal vesicles is associated with androgen withdrawal, while in the testis clusterin mRNA is repressed by cyclic AMP (cAMP). To understand the mechanisms that control the expression of the clusterin gene better, we isolated and characterized the gene encoding rat clusterin, and analysed its cytosine methylation pattern in various tissues. Several putative regulatory DNA elements were identified, including a consensus AP-1 site in the 5' flanking region. Two AP-1 sites and two transforming growth factor-beta inhibitory elements, one AP-2 site and eight half-sites for glucocorticoid/androgen response elements were found within the first intron, and one cAMP response element was found in the first exon. The cytosine methylation pattern indicated that testicular or epididymal DNA in the rat is hypomethylated in the region between positions -534 and -99 of the clusterin gene, when compared with tissues with lower levels of expression such as prostate as well as liver, lung, kidney and spleen.
J Mol Endocrinol 1994 Aug
PMID:Regulators for the rat clusterin gene: DNA methylation and cis-acting regulatory elements. 799 55

New N-substituted arylthiohydantoin antiandrogens were synthesized. These compounds presented exceptionally high relative binding affinities (RBAs) for the rat androgen receptor (AR): up to 3 times that of testosterone (T) and 100 times the RBAs of non-steroidal antiandrogens such as flutamide, Casodex and Anandron. Furthermore, unlike available markers for AR, they were totally devoid of any binding to the other steroid receptors. RU 59063, the molecule with the highest RBA, was tritiated. When it was compared to [3H]T for the assay of rat, mouse, hamster and human AR, it gave rise to the same number of binding sites but its K alpha (6 x 10(9) M-1) for rat and human AR were, respectively 3 and 8 times higher than that of T. Moreover RU 59063, unlike T, was devoid of any specific binding to human plasma. In vivo, these compounds displayed antiandrogenic activity while being devoid of any agonistic effect. Thus, RU 56187, given orally in castrated male animals, prevented in a dose-dependent manner the effects of 3 mg/kg testosterone propionate (TP) on mouse renal ornithine decarboxylase (acute test) and of 0.5 mg/kg TP on rat prostate weight (chronic test). In these two models, its ED50 was 0.6 and 1 mg/kg, respectively. In the intact rat, when given alone, it inhibited dose-dependently the effect of endogenous androgens on the seminal vesicles (ED50 approximately 1 mg/kg) and prostate (ED50 approximately 3 mg/kg) weights. These results suggest that these new compounds may be useful as specific markers for the androgen receptor as well as for the treatment of androgen-dependent diseases or disorders such as prostate cancer, acne, hirsutism and male pattern baldness.
J Steroid Biochem Mol Biol 1994 Jan
PMID:Non-steroidal antiandrogens: synthesis and biological profile of high-affinity ligands for the androgen receptor. 813 96

An expression cassette carrying 426 basepairs of the rat probasin (PB) gene promoter and 28 basepairs of 5'-untranslated region is sufficient to target the expression of the bacterial chloramphenicol acetyltransferase (CAT) gene specifically to the prostate in transgenic mice. The PB-CAT transgene was expressed in three of five (60%) independent lines of mice, and this expression, as reported previously for the endogenous rat gene, was male specific, restricted primarily to the lateral, dorsal, and ventral lobes of the prostate, with only very low levels of CAT activity detected in the anterior prostate and seminal vesicles. The developmental and hormonal regulation of the transgene also paralleled that reported for the rat gene, with a 70-fold increase in CAT activity in the mouse prostate observed between 2-7 weeks of age, a time corresponding to sexual maturation. PB-CAT activity in the prostate declined after castration to 3.5% of the precastration level, and the CAT activity in castrated males approached precastration levels when mice were supplemented with testosterone. Transgene expression in castrated males was not induced by dexamethasone. Coinjection of PB-CAT with a chicken lysozyme gene matrix attachment region resulted in their cointegration and further restricted the pattern of PB-CAT to the dorsolateral prostate, with suppressed expression observed in the ventral prostate. These studies demonstrate that a minimal rat probasin promoter can target heterologous gene expression specifically to the prostate in a developmentally and hormonally regulated fashion.
Mol Endocrinol 1994 Feb
PMID:The rat probasin gene promoter directs hormonally and developmentally regulated expression of a heterologous gene specifically to the prostate in transgenic mice. 817 Apr 79

Effects of prolactin(Prl), bromocriptine(Br), testosterone propionate (TP), dihydrotestosterone (DHT) and combinations of these androgens with Prl/Br on the maximum catalytic capacities of seminal vesicular enzymes involved in the glycolytic and pentose phosphate pathways in castrated mature monkeys were studied. Castration decreased the activities of all of the enzymes studied such as hexokinase(HK), 6-phosphofructokinase(PFK), glyceraldehyde-3-phosphate dehydrogenase(G3PD), pyruvate kinase(PK), glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase(6PGD) in the seminal vesicles. Prl restored the activities of all of the enzymes to their normal values except G3PD. TP/DHT maintained all the enzyme activities at the normal tissue intact level. Prl given along with androgens further enhanced the androgen action with regard to all the enzymes activities except G3PD. Br decreased all of the enzymes but Br with androgens maintained all the enzyme activities at the normal level. Castration decreased significantly serum T/DHT titres but Prl did not alter Prl levels. Prl+TP/DHT elevated Prl levels. Br alone decreased serum Prl, T and DHT titres, but Br+TP/DHT decreased only Prl, elevated T and maintained DHT levels. These results suggest that Prl has a direct as well as a synergistic action with androgens on the activities of the enzymes of glycolysis and pentose phosphate pathways in the seminal vesicles of castrated monkeys.
Biochem Mol Biol Int 1993 Oct
PMID:Effects of prolactin and androgens on enzymes of carbohydrate metabolism in seminal vesicles of castrated mature bonnet monkeys, Macaca radiata. 827 11

We have investigated the origin of the sperm motility inhibitor (SPMI) from boar seminal plasma. SPMI was measured by its capacity to inhibit the motility of demembranated spermatozoa and by an enzyme-linked immunosorbent assay (ELISA). Among the various reproductive and now reproductive tissues and fluids tested, only the seminal vesicle fluid and seminal plasma contained significant amounts of SPMI biological activity and SPMI antigen. Like other seminal vesicle fluid proteins, SPMI is diluted 6- to 8-fold upon ejaculation. By immunohistochemical detection at the light microscope with antibodies obtained from rabbits immunized with SPMI purified from boar seminal plasma, SPMI was found in the cytosol and/or on the plasma membrane bordering the lumen of the seminal vesicles. At the electron microscope level, SPMI appeared to be present only on the surface of the secretory cells. The data indicate that SPMI originates from a single tissue, the seminal vesicle, and suggest that only the mature form present on the luminal surface of the gland can react with the antibody generated from rabbits immunized with the secreted form of SPMI.
Mol Reprod Dev 1993 Dec
PMID:Origin of a sperm motility inhibitor from boar seminal plasma. 830 10

PSP-I, a 13 kDa protein purified from boar seminal plasma, was found to have about 50% amino acid sequence homology with a family of zona pellucida-binding proteins known as spermadhesins. These proteins are produced by the accessory gland(s) of the male reproductive tract and coat the spermatozoa during ejaculation. In this study, we have investigated the possible biological functions of PSP-I using a solid-phase protein binding assay and its site of synthesis using both Western blot and immunocytochemical analyses. PSP-I was found to bind a number of proteins including endo-beta-galactosidase digested ZP3, soybean trypsin inhibitor, IgA, IgG and alpha-casein, indicating that it may have multiple functions. The protein or carbohydrate structures were not critical in the binding, since polyvinyl sulfate could effectively inhibit the binding of PSP-I to these proteins. Western blot analysis using specific antiserum to PSP-I showed that the protein was present in the seminal vesicle but not in the testes, epididymis or prostate. The protein was revealed by immunocytochemical analysis in the epithelium of seminal vesicles but not in the testes or the epididymis. It is concluded that PSP-I is synthesized by the epithelium of the seminal vesicles, secreted into the semen during ejaculation, and may be involved in various reproductive functions, such as preventing premature acrosome reaction and immunosuppression.
Mol Reprod Dev 1993 Jul
PMID:Binding characteristics and immunolocalization of porcine seminal protein, PSP-I. 835 28

In the male rat, testosterone has been shown to regulate gonadotrophin synthesis and secretion under experimental conditions such as castration or gonadotrophin-releasing hormone (GnRH) antagonist with or without testosterone. The present study aims at clarifying the effects of non-steroidal antiandrogens, Casodex and flutamide, and ethane dimethane sulphonate (EDS) on the regulation of gonadotropin synthesis and secretion. To enable a direct comparison within this study to expected effects of testosterone, a GnRH antagonist-treated group and a castrated group were included. The gene expression of the subunits was correlated with changes in the pituitary and plasma content of immunoreactive luteinizing hormone (LH) and follicle-stimulating hormone (FSH), free subunits and pituitary content of in vitro bioactive LH and FSH. Groups of ten male rats each received the following treatments for 7 days: (1) vehicle; (2) castration; (3) EDS (75 mg/kg); (4) GnRH antagonist (Cetrorelix 250 micrograms/kg/day), (5) Casodex (20 mg/kg/day) or (6) flutamide (20 mg/kg/day). The effectiveness of testosterone deprivation was demonstrated by the reduction of weight in androgen-dependent organs such as epididymides and seminal vesicles in the treated groups. Treatment with flutamide, EDS or castration significantly increased (p < 0.05) serum levels of LH, FSH and alpha-subunit, whereas serum gonadotrophin levels were decreased in the GnRH antagonist-treated group. alpha-Subunit mRNA levels were elevated in the castrated, EDS and flutamide group and LH-beta mRNA levels were increased in the castrated and EDS group. FSH-beta mRNA levels were increased in the castrated group and decreased in the GnRH antagonist group, but remained unchanged in the flutamide and EDS group.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1993 Feb
PMID:Effects of antiandrogens and ethane dimethane sulphonate (EDS) on gene expression, free subunits, bioactivity and secretion of pituitary gonadotrophins in male rats. 838 9

Two androgens, testosterone and dihydrotestosterone, are required for the development of the male urogenital tract in the rat. Testosterone is secreted by the fetal testes and is thought to elicit differentiation of the Wolffian ducts into seminal vesicles, vas deferens, and epididymides. Testosterone is converted into dihydrotestosterone by steroid 5 alpha-reductase in the urogenital tract, and this conversion is necessary for the differentiation of the prostate and external genitalia. Genes encoding two 5 alpha-reductase isozymes, designated type 1 and type 2, have been identified. We examined the expression and regulation of these genes on days 17-21 in the urogenital tracts of male and female fetuses. Expression of the type 1 gene predominated in epithelial cells, whereas type 2 gene expression was limited to mesenchymal cells. Surprisingly, this expression pattern was detected in both testosterone-dependent and dihydrotestosterone-dependent anlagen of the urogenital tract and was the same in both male and female fetuses. Furthermore, transcripts encoding the two isozymes were present in their respective cell types before the overt differentiation of internal genitalia. Androgens stimulated expression of the type 2 gene in the urogenital tracts of both sexes, but did not effect expression of the type 1 gene or the cell type-specific expression patterns of the 5 alpha-reductase genes. In the adult prostate, 5 alpha-reductase gene expression is under feedforward control, in which the product of the enzyme, dihydrotestosterone, stimulates the expression of the gene. However, no evidence for feedforward regulation of either 5 alpha-reductase gene was detected in the fetus.
Mol Endocrinol 1995 Nov
PMID:Expression and regulation of steroid 5 alpha-reductase in the urogenital tract of the fetal rat. 858 33

Our recent finding that diazepam-binding inhibitor/acyl-CoA-binding protein (DBI/ACBP) expression is regulated by androgens in the human prostatic adenocarcinoma cell line LNCaP, prompted us to study whether androgen regulation of DBI/ACBP also occurs in vivo in the prostate and in other organs of the rat. Northern blot analysis demonstrated that DBI/ACBP transcripts were expressed in male accessory sex organs such as ventral prostate, dorsolateral prostate, seminal vesicles and coagulating glands. Castration caused a 1.7- to 2.7-fold reduction in the levels of DBI/ACBP transcripts over a period of 6 days. Readministration of androgens during the last 3 days led to 4.2- to 7.5- fold higher levels of DBI/ACBP transcripts than in untreated castrates. In situ hybridization revealed that in the ventral prostate, DBI/ACBP transcripts were expressed predominantly in epithelial cells and that the observed effects of androgens were due both to modulation of gene expression per cell and to changes in cell composition. Androgen regulation of DBI/ACBP mRNA expression was also observed in the lacrimal glands, the adrenals, and the submandibular glands, but not in the liver and the kidney. These findings demonstrate that DBI/ACBP is androgen-regulated in vivo in various organs of the rat. In view of the proposed role of DBI/ACBP in the control of multiple biological processes, DBI/ACBP may be one of the target genes by which androgens affect a variety of physiological processes.
Mol Cell Endocrinol 1996 Apr 19
PMID:Androgen regulation of the messenger RNA encoding diazepam-binding inhibitor/acyl-CoA-binding protein in the rat. 873 92

Both sexes of adult mice homozygous for a targeted mutation of the Igf1 gene, encoding insulin-like growth factor 1, are infertile dwarfs (approximately 30% of normal size). The testes are reduced in size less than expected from the degree of dwarfism but sustain spermatogenesis only at 18% of the normal level. The epididymides are overall nearly allometric to the reduced body weight, but the distal regions of the duct, vas deferens, seminal vesicles, and prostate are vestigial. Despite the mutational impact on the epididymis, capacitated sperm are able to fertilize wild type eggs in vitro. It is hypothesized that the infertility of male mutants is caused by failure of androgenization resulting in absence of mating behavior, due to drastically reduced levels of serum testosterone (18% of normal). This hormonal deficiency was correlated with an ultrastructural analysis of mutant Leydig cells revealing a significant developmental delay, while assays in organ culture showed that the basal and LH-stimulated production of testosterone by testicular parenchyma is reduced in comparison with wild type controls. The female mutants fail to ovulate even after administration of gonadotropins, which is apparently the primary cause of their infertility, and possess an infantile uterus that exhibits a dramatic hypoplasia especially in the myometrium. The phenotypic manifestations of the mutation were correlated with the localization of transcripts for insulin-like growth factor I and its cognate receptor in wild type reproductive tissues by in situ hybridization.
Mol Endocrinol 1996 Jul
PMID:Effects of an Igf1 gene null mutation on mouse reproduction. 881 30


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