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)

Sixteen dicyclohexane derivatives including the parent compound d,1-3,4-bis (4-oxocyclohexyl)-hexane (PRDX) have been synthesized and studied for putative interference with androgen binding to transport proteins, metabolizing enzymes, and receptors from rat tissues. Several of these analogues inhibited competitively the binding of dihydrotestosterone to ABP, the epididymal androgen transport protein. One compound had an affinity for ABP as high as Kd = 70 nM. Some dicyclohexanes also inhibited the aromatase enzyme which catalyses conversion of androgens into estrogens, as well as the NADPH-dependent, particulate form of 3 alpha(beta)-hydroxysteroid dehydrogenase, the enzyme that converts dihydrotestosterone into 5 alpha-androstanediol. For both enzymes the inhibition potency Ki of PRDX was about equal to the Km of the substrate. All of these interactions were specific in that they were modulated by single substitutions on the dicyclohexane molecule and they did not occur with other steroid binding proteins such as 5 alpha-reductase and the intracellular androgen receptor. A conformational study showed that dicyclohexanes can assume a 'steroidoid' conformation that differs from the crystal structure and which could account for the specific interactions with the steroid binding sites described here.
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PMID:Inhibition of steroid-protein interactions by dicyclohexane derivatives. 319 13

A composite androgen receptor DNA sequence 4,181 base pairs in length was determined from three cDNA clones isolated from a rat epididymal bacteriophage lambda gt11 library. An open reading frame of 902 amino acids encodes a protein of 98,227 mol wt. Structural domains characteristic of the steroid receptor family include an amino-terminal region with five repeated amino acid motifs, a central DNA-binding domain homologous with other steroid receptors, and a carboxyl-terminal steroid-binding region. A receptor cDNA probe used in Northern blot analysis hybridized with a predominant 10-kilobase androgen receptor mRNA in male reproductive tissues of the rat. Autoregulation of androgen receptor mRNA was indicated in rat ventral prostate by an increase in the level of 10-kilobase mRNA after castration and suppression of receptor mRNA upon androgen restimulation. A 15 amino acid peptide with sequence derived from the deduced androgen receptor sequence was synthesized and used as immunogen in raising receptor antibodies in rabbits. Antisera reacted with high titer against the synthetic peptide by enzyme-linked immunosorbent assay and against the native [3H]dihydrotestosterone-labeled androgen receptor as evidenced by an increase in receptor sedimentation rate determined by sucrose gradient centrifugation. Immunocytochemical staining localized the androgen receptor to epithelial cell nuclei in rat ventral prostate.
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PMID:The rat androgen receptor: primary structure, autoregulation of its messenger ribonucleic acid, and immunocytochemical localization of the receptor protein. 321 67

Rams were randomly assigned to an experiment that evaluated effects of treatment (2.5 mg melatonin/d for 45 d vs control; MEL vs CON) in mid-May through June on testis weight and concentration of epididymal androgen receptor in July or September (Sept). Mean testis weight of MEL and CON rams was not different in July (332 vs 283 g), but in Sept was less (P less than .05) for MEL rams than CON rams (268 vs 382 g). Testis weight of MEL rams was less (P less than .05) in Sept than in July. Caput, corpus and cauda epididymal tissues were used to prepare extracts which were analyzed for concentration of dihydrotestosterone (DHT) receptor using a new standard curve method. A standard extract was characterized using four independent 8-point Scatchard analyses and found to contain 6.0 fmol DHT receptor/mg wet tissue (Ka = 3.5 X 10(8).M-1); this extract was used to establish standard curves for assays of unknown samples. Data on concentration of DHT receptors measured by Scatchard analysis and the standard curve method were highly correlated (r = 0.99; P less than .01; n = 8). Concentrations of DHT receptor were not affected by treatment, month of castration, or their interaction. However, for data pooled across treatment and month, concentration (fmol/mg protein) of DHT receptor was greater (P less than .05) in caput or corpus (125 or 122) than in cauda (92) epididymidis. The regional distribution of epididymal DHT receptors in this study confirmed our previous findings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of exogenous melatonin prior to the breeding season on testis weight and epididymal androgen receptors in rams. 322 26

The photoperiodic influence (LD 16:8 long photoperiod, LD 8:16 short photoperiod) on the morphology and the androgen receptor level of the epididymis and the ductus deferens of Phodopus sungorus was investigated. Under short day-conditions, the wet weight of the epididymis is reduced to 5-6%, the diameter of the epididymal duct and of its lumen are reduced, the height of the epithelium and the thickness of the smooth muscle layer are increased. Number and size of epithelial and smooth muscle cells are not changed, no atrophy of the smooth muscle cells is found. The loss in wet weight during short photoperiods is discussed in relation to the loss of stored sperm and luminal fluid. The wet weight of the ductus deferens is decreased to about 30% at short photoperiods, the total length of the organ, its diameter and the luminal diameter are decreased. The height of the epithelium is slightly, and the thickness of the smooth muscle layer is strongly, reduced, the latter due to an enormous atrophy of the smooth muscle cells. The androgen receptor content of the epididymis (per pair of organs) is reduced to about 5%, that of the ductus deferens to about 10% of the values found at long photoperiods, indicating a significant loss of androgen receptors with low circulating androgen levels.
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PMID:Influence of long and short photoperiods on the morphology and androgen receptor levels of the epididymis and the ductus deferens of Phodopus sungorus. 322 15

To provide insight into the mechanism of wolffian duct virilization the androgen receptor has been characterized in pooled epididymal tissue from Day 27 rabbit embryos. Although the receptor is present at levels about a tenth that of other androgen target tissues in rabbit embryos, it appears to be a typical androgen receptor in regard to sedimentation characteristics and preferential binding of 5 alpha-dihydrotestosterone over testosterone. Thus, the mechanism by which testosterone virilizes the wolffian duct cannot be explained by unique binding characteristics of the androgen receptor in tissues derived from the wolffian ducts.
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PMID:The androgen receptor in the fetal epididymis is similar to that in the mature rabbit. 342 Jan 14

The mechanism of the antiandrogenic effect of 5,10-seco-19-norpregnane-4,5-diene-3,10,20-trione (secosteroid), reputedly an irreversible inhibitor of 5 alpha-reductase, was investigated. Its addition (10 microM) to culture media effectively suppressed the synthesis of rat epididymal proteins specifically induced by 0.1 microM testosterone (T) or dihydrotestosterone (DHT). Under the same conditions, secosteroid did not change the rate at which labeled T was metabolized to 5 alpha-reduced compounds. In a comparative study, secosteroid inhibited 5 alpha-reductase in an isolated microsomal fraction while not affecting the enzyme activity in minced tissue. Secosteroid was shown to be a competitor of the binding of [3H]T and [3H]DHT (both at 4 nM) to the epididymal cytosol androgen receptor, with ID50 of 1 microM for the former and 4 microM for the latter, thus explaining the mechanism involved in its antiandrogenic properties.
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PMID:Studies on the mechanism of the antiandrogenic effect of a putative 5 alpha-reductase inhibitor. 362 56

Protein-bound steroids can be separated from free steroids using microcolumns of silica gel coated with an hydrophobic (octadecyl) solid phase. The bound fraction is eluted in the assay buffer, whereas the free fraction is retained quantitatively on the column in the first step and can be recovered in methanol. Both fractions can be quantitated directly (e.g. by liquid scintillation spectrometry when using radioactive ligands) or kept for further analysis (e.g. by TLC, HPLC etc.). Separation of the bound and free fractions is rapid, accurate and reproducible; intra- and inter-assay coefficients of variation are lower than 5 and 10%, respectively. Recovery of radioactive steroids is high (usually over 85%) and can be estimated separately for each sample. Since assay blanks are very low (typically less than 0.1% of input), this new method, which could be termed "hydrophobic interaction chromatography" (HIC), should prove especially useful for the development of sensitive binding assays, particularly in the field of steroid receptors. The HIC method compared well with three methods currently used for steroid binding assays, namely adsorption of unbound steroids on dextran-coated charcoal, gel filtration on Sephadex LH-20 and adsorption of steroid-protein complexes on DEAE-cellulose filters. Examples of application described here include studies on human plasma sex hormone binding globulin (SHBG) and SP2 placental protein (saturation analysis, binding specificity etc.), the separation of antibody-bound steroids in a radioimmunoassay and the estimation of androgen binding to rat epididymal androgen binding protein (rABP). Receptor assays are illustrated by saturation analysis of the mouse uterine oestrogen receptor and of the androgen receptor in the human genital skin.
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PMID:Hydrophobic interaction chromatography (HIC) for the separation of protein-bound and free steroids. Application to binding protein and receptor assays. 409 24

In the framework of a study on nonsteroidal androgens, the authors previously observed that in perhydrohexestrol series, the (+/-)-[(cis-4 hydroxycyclohexyl)-4(trans-4 hydroxycyclohexyl)-hexane] or cis-trans perhydrohexestrol and especially the (+/-)-(3,4 bis (trans-4-oxocyclohexyl)-hexane) or trans-trans perhydrodiketone, there is no affinity for AR (androgen receptor of the prostate) but they bind with high and specific affinity to the testosterone binding sites on ABP (epididymal androgen-binding protein). In this work, we describe the preparation, the stereochemistry and biological activities of trans-trans and cis-trans perhydrohexestrols and of trans-trans perhydrodiketone as well as their corresponding enantiomers. Biologically the tests AR and ABP are negative for the trans-trans perhydrohexestrol and of trans-trans perhydrodiketone and for its enantiomers. However for the enantiomers of cis-trans perhydrohexestrol and of trans-trans perhydrodiketone, the affinity of the (+) enantiomer for ABP is superior to that of the racemic and that of the (-) enantiomer, whereas the affinity for AR are zero. Chemically, the stereochemistry of the three racemics has been established by X-ray crystallographic analysis or by 1H n.m.r. The n.m.r. spectra have been analyzed in terms of chemical shifts and coupling constants.
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PMID:[Steroid ligands of androgen binding protein. The enantiomers of trans-trans and cis-trans perhydrohexestrols and trans-trans perhydrodiketones]. 628 5

The effects of estradiol-17 beta on androgen uptake, metabolism and binding were studied in rat epididymis in vivo in comparison with cyproterone acetate. Steroids (250 ug/100 g body weight) were injected 5 min prior to 3H-testosterone in castrate rats. Estradiol-17 beta inhibited 3H-testosterone uptake into epididymal cytosol by 58% as compared to 38% by cyproterone acetate. 3H-Testosterone uptake into epididymal nuclei was inhibited 95% by estradiol-17 beta and 83% by cyproterone acetate. Total bound radioactivity in cytosol fractions was reduced to a greater extent by estradiol-17 beta than cyproterone acetate when either 3H-testosterone or 3H-dihydrotestosterone was injected. Binding of 3H-dihydrotestosterone to nuclear receptors was completely abolished by estradiol-17 beta; whereas approximately 20% binding remained in the nuclear extract after cyproterone acetate treatment. Metabolism of 3H-testosterone in vivo was also altered by estradiol-17 beta, resulting in diminished conversion to 3H-dihydrotestosterone. Cyproterone acetate, on the other hand, did not affect 3H-testosterone metabolism. Estradiol-17 beta and cyproterone acetate inhibited in vitro binding of 3H-dihydrotestosterone to the intracellular cytoplasmic receptor, but not the intraluminal androgen binding protein (ABP). These data suggest that estradiol-17 beta may have a more potent antiandrogenic effect on the epididymis than cyproterone acetate due to inhibition of 5 alpha reduction of testosterone as well as binding to the androgen receptor.
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PMID:Estradiol-17 beta inhibition of androgen uptake, metabolism and binding in epididymis of adult male rats in vivo: a comparison with cyproterone acetate. 645 38

An androgen receptor (Rc) was demonstrated in caput, corpus and cauda epididymal cytosols of the ram. This receptor had a high affinity for 5 alpha-dihydrotestosterone (Kd = 5.2 X 10(-9) mol/l) and could be distinguished from the androgen-binding protein (ABP) by several characteristics. On polyacrylamide-gel electrophoresis, Rc had a mobility of 0.37 and ABP 0.61; Rc sedimented in the 9S region of a linear sucrose gradient whereas ABP migrated in the 4.3S region; the molecular weights were 192 000 and 90 000 for Rc and ABP; their isoelectric points were 5.7 and 4.8-5.0; they were proteinaceous components since they were destroyed by proteolytic enzymes and heating (50 degrees C for Rc and 60 degrees C for ABP); they exhibited different half-times of dissociation:20 h at 0 degree C for Rc and 6 min for ABP, which is in agreement with their respective physiological roles, intra- and extracellular transport of androgens. The content of Rc-binding sites in caput epididymis was 18, in corpus 4 and in cauda 22 fmol/mg protein.
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PMID:Androgen-binding proteins in sheep epididymis: characterization of a cytoplasmic androgen receptor in the ram epididymis. 654 24


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