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)

After i.m. injection of [3H]butyrobetaine into intact and castrated rats, the specific activity of plasma carnitine remained nearly constant over 24--96 h and epididymal uptake of carnitine was constant per unit time up to 72 h. The uptake ratio of intact to castrated rats was high at 48, 72 and 96 h after injection. Administration of estradiol valerate over 20 days reduced carnitine uptake in epididymis. This reduction was dose-dependent when estrogen was administered i.m. at 0.33--10 microgram/day levels. A maximum reduction of 90% was obtained with the 10 microgram dose. A dose increase from 33 to 100 microgram/day caused no further reduction. Norspiroxenone (2--10 mg/day) and SK 7670 (1.5 and 7.5 mg/day) were less effective than estradiol valerate (10 microgram/day) in suppressing carnitine uptake in epididymis. Epididymal carnitine uptake in estradiol valerate treated rats (33 microgram/day for 20 days) increased in a time- and dose-dependent manner under testosterone propionate treatment (50, 250, 1250 microgram/day). Carnitine uptake increased to 80% of the nonsuppressed levels when testosterone propionate was adminsitered over a 6-day period at 1250 microgram/day. Dihydrotestosterone increased epididymal carnitine uptake to the same extent as testosterone propionate. delta4-androstene-3,17-dione and 5alpha-androstane-3alpha,17beta-diol (50 microgram/day) were less effective, stimulating uptake to only 15% and 40% respectively of the testosterone propionate (250 microgram/day) stimulated levels. Changes in epididymal carnitine uptake evoked by various experimental procedures were closely paralleled by weight changes in the ventral prostate. This response resemblance indicates a similarity between the androgen sensitivity of the prostate gland and that of the carnitine uptake system in epididymis. The dose-dependent effect of estrogen on the accumulation of epididymal carnitine, together with the marked responses induced in this system by manipulation of its androgen status, support a possible use for the system as an assay for androgen or antiandrogen potency in vivo.
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PMID:Accumulation of carnitine in rat epididymis after injection of [3H]butyrobetaine in vivo: quantitative aspects, and the effects of androgens and antiandrogens. 68 Mar 41

The pattern of androgenic metabolites in blood, muscle, caput and cauda epididymidis has been investigated in functionally hepatectomized 24 hours castrated rats, 3 hours after the intra-muscular injection of 200 muCi of 3H-3H-3alpha-diol. Identification of the radioactive metabolites showed only negligible differences between the epididymal regions. In both caput and cauda the main metabolite was DHT (17beta-hydroxy-5alpha-androstane-3-one); 3alpha- and 3beta-diol, androsterone (3alpha-hydroxy-5alpha-androstane-17-one), 5-A-dione (5alpha-androsterone-3, 17-dione), delta16-3alpha-01 (kalpha-androst-16-en-3alpha-01), delta16-3beta-01 (5alpha-androst-16-en-3alpha-01) and delta16-3-one (5alpha-androst-16-en-3-one) were also present. Androsterone and 3alpha-diol were the predominant metabolites in blood and muscle. No delta16 compounds could be detected and in constrast to epididymis, more than 50% of the radioactivity was associated with polar compounds. From determination of total radioactivity, it was seen that retention by epididymis varied from two to four times that of muscle. Purification and identification of the radioactivity associated with the nuclear fraction demonstrated that DHT was the only nuclear bound androgen. It is suggested from these results that at least one effect of 3alpha-diol on the rat epididymis is exerted through its conversion to DHT.
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PMID:Androgen metabolism by rat epididymis. 5. Metabolic conversion and nuclear binding after injection of 5alpha-androstane-3alpha, 17beta-diol, in vivo. 101 38

The in vivo and in vitro metabolism of 3H-testosterone by rat epididymis and the changes in epididymal weight have been studied after castration and treatment with anti-androgens. The utilization of 3H-testosterone was greatly reduced after castration as was the formation of 5alpha-reduced 17 beta-hydroxy metabolites. The formation of the 17 -keto metabolites was unaffected. Castration had no effect on the ratio between water and ether soluble radioactivity. Administration of testosterone propionate, necessary for giving normal stimulated prostate weight (150 mug/day), restored the metabolism of testosterone to approximately normal values. Estradiol benzoate and progesterone inhibited metabolism of testosterone in vitro and greatly reduced the formation of DHT (17 beta-hydroxy-5alpha-androstan-3-one) and 3 alpha-diol(5 alpha-androstane-3 alpha-17 beta-diol) by experiments both in vivo and in vitro. No effect of cyproterone acetate could be demonstrated on either the in vitro or in vivo metabolism of testosterone. Castration for 14 days reduced the epididymal weight to about 30% of that found in intact animals. Administration of testosterone propionate restored the epididymal weight to about 80% of normal. Estradiol benzoate and cyproterone acetate given to intact rats led to a decrease in the epididymal weight. Progesterone had no such effect. In 14 days castrated rats receiving testosterone propionate all three anti-androgens reduced the weight of the epididymis. In conclusion, our results show that the metabolic conversion of testosterone in epididymis to DHT and 3 alpha-diol is dramatically dependent on the hormonal status of the animal; castration or treatment with anti-androgens causes a reduced formation of the "active" androgens whilst testosterone replacement treatment restores the metabolism of testosterone to normal.
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PMID:Androgen metabolism by rat epididymis. 3. Effect of castration and anti-androgens. 126 92

The effect of several synthetic steroids belonging either to the 4-aza-3-oxo-steroid family or to androstene and androstane derivatives was investigated "in vitro" on the epididymal as well as prostatic 5 alpha-reductase activity. For this purpose rat caput epididymis and prostate were incubated with the different steroidal compounds at molar concentrations of 10(-7), 10(-6), and 10(-5) in the presence of labelled testosterone as substrate. The steroids 4-MA (17 beta, N,N-diethyl-carbamoyl-4-aza-5 alpha-androstan-3-one) and 4-OH-A (4-hydroxy-androstenedione), already known to be effective 5 alpha-reductase inhibitors at the level of the prostate, have been used as reference molecules. The 5 alpha-reductase activity was evaluated by measuring pg of dihydrotestosterone (DHT) formed in 2 h of incubation by mg of tissue. The steroids A, B, C, F, G and I inhibit the formation of DHT in the rat epididymis although to different extents; they are also equally effective on the formation of DHT in the rat prostate. The steroids D, E, H and L are devoid of any inhibitory property on the formation of DHT in both the rat epididymis and prostate. The most interesting results were obtained with compound M which exhibits a dose-dependent and significant inhibitory effect on the formation of DHT in the epididymis, but it is inactive at the level of the prostate. These findings suggest that it is possible (a) to selectively interfere with the 5 alpha-reductase of the epididymis without affecting that present in the prostate, and (b) consequently to envisage new ways to regulate male fertility.
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PMID:Selective inhibition of the 5 alpha-reductase of the rat epididymis. 161 80

Multiple forms of the soluble 17 beta-hydroxysteroid dehydrogenase of female rabbit liver were identified. NAD-dependent and NADP-dependent enzyme activities were separated by affinity chromatography on agarose-immobilized Procion Red HE3B, and three forms of the NADP-dependent enzyme activity were purified by chromatofocusing. These three enzyme forms are charge isomers and have no quaternary structure. The enzymes catalysed the C-17 oxidoreduction of oestrogens and androgens; with all enzyme forms the activity towards androgens was higher than that toward oestrogens. The enzymes also exhibited 3 alpha-hydroxysteroid dehydrogenase activity towards androgens of the 5 beta-androstane series. Comparison of the relative activities of the enzymes towards a number of oestrogen and androgen substrates revealed differences among the enzyme forms for both the oxidative and the reductive reactions. In particular, one enzyme form had a significantly lower Km for the 3 alpha-hydroxysteroid substrate and a higher 3 alpha-/17 beta-hydroxysteroid dehydrogenase activity ratio than the other two enzyme forms.
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PMID:A 17 beta-hydroxysteroid dehydrogenase of female rabbit liver cytosol. Purification and characterization of multiple forms of the enzyme. 298 68

The concentrations of testosterone and its tissular metabolites were determined in testicular and epididymal tissue obtained from eleven male subjects (aged 65-85 years) after orchiectomy for prostatic cancer. The steroids were measured in different tissular compartments, i.e. testis, caput, corpus and cauda epididymis. The values (mean +/- SD; ng/g wet weight) were: Testosterone 724.0 +/- 286.0, 32.08 +/- 2.56, 41.45 +/- 1.77 and 32.24 +/- 2.14; 5 alpha-dihydrotestosterone 6.95 +/- 1.99, 9.76 +/- 2.33, 16.87 +/- 0.21 and 15.79 +/- 2.67; 5 alpha-androstane-3 alpha, 17 beta-diol 6.07 +/- 2.33, 2.17 +/- 0.24, 1.93 +/- 0.02 and 1.17 +/- 0.20; 5 alpha-androstane-3 beta, 17 beta-diol 56.66 +/- 20.97, 3.55 +/- 0.19, 2.21 +/- 0.27 and 3.34 +/- 0.32; estradiol-17 beta 5.36 +/- 3.0, 1.08 +/- 0.014, 1.44 +/- 0.038 and 1.47 +/- 0.03, respectively. Incubation of human testicular tissue with [3H]androst-5-ene-3 beta, 17 beta-diol or [3H]dihydrotestosterone showed that both androstane-diols were exclusively formed from dihydrotestosterone. Since high concentrations of 5 alpha-androstane-3 beta, 17 beta-diol are found in testicular tissue it is suggested that this steroid may be an index of seminiferous tubular function.
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PMID:Concentrations of unconjugated 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol and their precursor in human testicular tissue. Comparison with testosterone, 5 alpha-dihydrotestosterone, estradiol-17 beta, and with steroid concentrations in human epididymis. 358 50

We have investigated the effects of two 4-ene-steroid 5 alpha-reductase inhibitors, diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA) and (4R)-5,10-seco-19-norpregna-4, 5-diene-3,10,20-trione (SECO), on testicular and epididymal androgen biosynthesis. Kinetic analyses revealed that both compounds inhibited epididymal DHT biosynthesis. 4-MA was a competitive inhibitor of epididymal nuclear and microsomal 4-ene-steroid 5 alpha-reductases (3-oxo-5 alpha-steroid: NADP 4-ene-oxidoreductase EC 1.3.1.22) with Kiapp values of 12.8 and 15.1 nmol/l compared to the respective Kmapp values of 185 and 240 nmol/l. Values for the Vmaxapp were always within 70-130% of the control. SECO at 1.0 mumol/l, also inhibited epididymal nuclear and microsomal 4-ene-steroid-5 alpha-reductases, causing respectively 2.9 and 5.2-fold increases in Kmapp. The Vmaxapp values were unchanged. However, SECO concentrations of 5 and 25 mumol/l abolished 4-ene-steroid 5 alpha-reductase activity at all testosterone concentrations. To examine the specificity of these compounds, we investigated their effects on the enzymes that convert pregnenolone to testosterone. Rat testis microsomes converted pregnenolone to testosterone via the 4-ene-3-oxo pathway, with the major metabolites being progesterone, 17-hydroxyprogesterone, 4-androstenedione and testosterone; some 17-hydroxypregnenolone was also formed. Very small amounts of dehydroepiandrosterone (DHA) and 5-androstenediol were detected. SECO, at a concentration that completely inhibited epididymal 4-ene-steroid 5 alpha-reductase activity, did not alter the metabolic profile of pregnenolone metabolism. However, 4-MA prevented the appearance of 4-ene steroids, and large quantities of 17-hydroxypregnenolone and DHA accumulated, suggesting that inhibition of the 3 beta-hydroxysteroid: NAD(P)+ oxidoreductase (EC 1.1.1.51) and 3-oxosteroid 5-ene-4-ene-isomerase (EC 5.3.3.1) [3 beta-hydroxysteroid dehydrogenase-isomerase] was occurring. Optimal conditions for the microsomal conversion of DHA to 4-androstenedione were determined; kinetic analyses of the 3 beta-hydroxysteroid dehydrogenase-isomerase activity revealed that 4-MA inhibited this reaction non-competitively, reducing Vmaxapp values to 25% of the control. The Kiapp determined from the intercept replot, was 121 nmol/l, and the Kmapp was always between 90 and 130% of the control value. It is concluded that SECO is more specific than 4-MA in its effects on androgen biosynthesis in the testis and epididymis and that both these drugs should provide useful tools in assessments of the relative contributions of 5 alpha-reduced androgens to androgen dependent processes.
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PMID:The effects of diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide (4-MA) and (4R)-5,10-SECO-19-norpregna-4,5-diene-3,10,20-trione (SECO) on androgen biosynthesis in the rat testis and epididymis. 370 62

We report here the structural assignment for the hydroxylated 5 alpha-reduced metabolites in the culture medium following incubation of radiolabelled testosterone with explants of rat ventral prostate, canine cauda epididymidis and prostate, and benign hyperplastic canine and human prostate. Explants were incubated for 21 h at 37 degrees C in surface contact with serum-free Trowell's T8 medium containing 1.7 microM or 8.5 nM substrate. After uptake determination, radiosteroid patterns in explants and media were obtained by t.l.c. The C19O3-metabolites released into the culture medium were resolved by h.p.l.c. and fractions migrating with appropriate reference compounds were crystallized to constant SA with carriers synthesized for this purpose. 5 alpha-Androstane-3 beta,6 alpha,17 beta-triol and 3 beta,6 alpha-dihydroxy-5 alpha-androstan-17-one were identified as the major C19O3-radiometabolites of rat ventral prostate. In the culture medium of canine prostate and epididymis and human prostate, 5 alpha-androstane-3 beta,7 alpha,17 beta-triol and 3 beta,7 alpha-dihydroxy 5 alpha-androstan-17-one were the principal hydroxylation products, with 6 alpha-hydroxy epimers as significant minor products of the canine prostate and epididymis and 5 alpha-androstane-3 beta,7 beta,17 beta-triol as a significant minor radiometabolite of human prostate tissue. Treatment of the castrated dog with androgen and estrogen causes an oxidative shift to striking predominance of 3 beta,7 alpha-dihydroxy 5 alpha-androstan-17-one. The 3 beta-hydroxy-5 alpha-androstane configuration of the identified C19O3-metabolites supports a pathway of prostatic and epididymal testosterone disposition which effects activation by 5 alpha-reductase and inactivation and egress by the coupled 5 alpha-3-oxosteroid reductase/3 beta-hydroxysteroid hydroxylase reactions.
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PMID:Metabolism of radiotestosterone to 3 beta,6 alpha- and 3 beta,7 alpha-dihydroxy 5 alpha-steroids by rat ventral, canine and human prostate in organ culture. 633 21

Human epididymal tubules from 9 patients undergoing orchidectomy were cultured for periods of up to 8 days with preservation of the histological structure of the tissue. Addition of androgens (testosterone, 5 alpha-dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-diol) significantly increased the epithelial height, the incorporation of [3H]amino acids and [3H]thymidine. The effect on protein synthesis was significant 48 h after the onset of treatment and was maximal after 3 days. The effect on DNA replication was maximal during the 3rd day of treatment. In both instances maximal activity was achieved at a concentration of 10(-7) M of testosterone. Cyproterone acetate (10(-5) M) was able to negate all effects of androgens.
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PMID:The organ culture of hunan epididymal tubules and their response to androgens. 645 2

We examined the influences of steroids present in the epididymis on androgen metabolism by epididymal tissue and on the binding of androgen metabolites to the epididymal androgen receptor in castrated adult rabbit epididymides under in vitro conditions. The conversion of [3H]testosterone to [3H]17 beta-hydroxy-5 alpha-androstan-3-one (5 alpha-DHT) and to [3H]5 alpha-androstane-3 alpha (beta), 17 beta-diol was inhibited by unlabeled steroids in the following manner progesterone greater than testosterone greater than estradiol. Unlabeled 5 alpha-DHT did not inhibit [3H]testosterone metabolism indicating that product inhibition is not an important regulatory event. The antiandrogen cyproterone acetate did not inhibit the formation of 5 alpha-reduced metabolites of [3H]testosterone. All of the compounds used inhibited androgen binding to the classically defined cytoplasmic and nuclear androgen receptor.
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PMID:The effects of various steroids on testosterone metabolism by the sexually mature rabbit epididymis. 654 32


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