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)

The effect of simvastatin (MK-733), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on plasma triacylglycerol (TG) levels was studied in rats. Dietary administration of MK-733 (0.055%, w/w) for 7 days significantly (P less than 0.05) reduced plasma TG levels by 30.6% associated with a 44.3% significant (P less than 0.01) reduction in very low density lipoprotein TG (VLDL-TG) as compared to those in the concurrent control rats. Clofibrate (0.08%, w/w) also significantly (P less than 0.05) decreased plasma TG levels by 26.1%. MK-733 did not affect the triacylglycerol secretion rate (TGSR) during 0-1.5 hr after administration of Triton WR-1339, but reduced it by 33.9% during 1.5-3.0 hr. Clofibrate also decreased TGSR during 1.5-3.0 hr. MK-733 increased lipoprotein lipase (LPL) activity in epididymal adipose tissue and thigh muscle by 36.3 and 55.0% respectively. MK-733 significantly (P less than 0.05) increased LPL activity in the post-heparin plasma by 21.5%, although it did not affect hepatic triacylglycerol lipase (H-TGL) activity. Clofibrate did not affect LPL activity in the tissues or LPL and H-TGL activities in the post-heparin plasma. It is considered that the mechanism of plasma TG-lowering effect of MK-733 is the removal of VLDL-TG by an increase in LPL activity in the tissues as well as a decrease in the TGSR.
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PMID:Effect of simvastatin (MK-733) on plasma triacylglycerol levels in rats. 200 92

Epididymal nuclear 5 alpha-reductase enzyme activity is regulated by a testosterone-dependent factor from the testis. Regulation at the mRNA level, however, has not been investigated. Endocrine manipulation experiments were designed to determine whether 5 alpha-reductase is regulated at the steady state mRNA level. Steady state mRNA concentrations were assessed using the full-length cDNA for female rat liver 5 alpha-reductase. Longitudinal distribution showed that the highest mRNA concentrations were present in the initial segment of the caput epididymidis and were 3- to 7-fold higher than in the other tissue segments. The androgen dependence of the mRNA levels for 5 alpha-reductase was assessed by bilateral orchidectomy and simultaneous testosterone replacement therapy. One week after surgery, mRNA concentrations in orchidectomized rats were decreased to 15% of control levels in the initial segment of the caput epididymidis and to 40-50% of control levels in the remaining epididymal segments. Administration of testosterone at a dose that mimics normal serum concentrations (2.5-cm Silastic implant) restored 5 alpha-reductase mRNA concentrations to control levels in the corpus and cauda epididymidis, but these were not significantly different from orchidectomized levels (P greater than or equal to 0.05) in the initial segment and caput epididymidis. Administration of testosterone at a dose designed to approximate 5- to 8-fold normal serum concentrations (18.6-cm implant) maintained 5 alpha-reductase mRNA concentrations at only 50% of control levels in the initial segment, while complete maintenance was observed in the rest of the tissue. The effects of unilateral orchidectomy revealed that 5 alpha-reductase mRNA concentrations decrease selectively in the initial segment of the orchidectomized side. This is the first report that epididymal 5 alpha-reductase is regulated at the mRNA level and that the regulation is different with respect to the segment being studied.
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PMID:Differential regulation of steady state 4-ene steroid 5 alpha-reductase messenger ribonucleic acid levels along the rat epididymis. 201 58

We measured androgen receptors (AR) and 5 alpha-reductase activity (5 alpha RA) in the ductuli efferentes and epididymides from adult rhesus macaques. Tissue samples were either assayed biochemically for AR or stained immunocytochemically (ICC) with a monoclonal antibody against AR. To estimate 5 alpha RA, tissue microsomes were incubated with [1 alpha,2 alpha-3H]testosterone, and the [3H]dihydrotestosterone formed was quantified. We found significant regional differences in the levels of both 5 alpha RA and AR in the excurrent ducts. In general, both enzyme activity and AR levels were higher in the caput and corpus epididymis than in ductuli efferentes and cauda epididymis. With ICC, positive nuclear AR staining was detected in all epithelial cell types, whereas variable numbers of stromal cells were positively stained. Our data demonstrate that there are segmental differences in the concentrations of 5 alpha RA and AR in epididymis and suggest that there may be regional differences in the regulation of epididymal functions by androgen.
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PMID:Androgen receptor and 5 alpha-reductase activity in the ductuli efferentes and epididymis of adult rhesus macaques. 204 44

A surgical technique to cannulate the rete testis of the goat was utilized to examine the effects of rete testis fluid (RTF) deprivation on the enzymatic activity of epididymal 5 alpha-reductase. Kinetic techniques were used to determine whether the regional enzymatic effect of RTF deprivation is to decrease the apparent number of 5 alpha-reductase active sites or the catalytic activity of each active site within the epididymal epithelium. Paired comparisons of (Vmax)app and (Km)app values between control and RTF-deprived epididymides indicated that RTF deprivation affected the value of (Vmax)app with no apparent change in the values of (Km)app in caput, corpus, and cauda epididymal regions. We conclude that RTF deprivation in the goat epididymis for 7 days results in a decreased number of apparent 5 alpha-reductase active sites within the epididymal epithelium.
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PMID:Influence of rete testis fluid deprivation on the kinetic parameters of goat epididymal 5 alpha-reductase. 230 55

In an attempt to understand the mechanism(s) responsible for the reported marked seasonal increase in prostatic, but not epididymal, weight in T. vulpecula, a number of parameters were measured in tissues from mature, entire males sampled within and outside of the breeding season and from castrates. Conditions for the measurement of cytosol androgen receptors were also established. The weight of both the prostate and the epididymis was significantly elevated in the breeding season but the relative increase in prostate weight was considerably greater. The increase in prostatic weight was associated with a decrease in DNA: g tissue and an increase in protein: DNA and RNA: DNA ratios, each indicative of cellular hypertrophy and/or accumulation of secretory product. In the epididymis there were no significant seasonal changes in RNA: DNA, protein: DNA or DNA: g tissue ratios. Low-capacity, high-affinity binding was demonstrated in the epididymal and prostatic cytosols and values for the equilibrium association constants and receptor concentrations were within the range reported for androgen receptors in eutherian species. The temperature sensitivity of the binding, steroid specificity and slow dissociation in the cold indicated that in both tissues cystosol receptor and not androgen-binding or serum-binding protein(s) were being measured. In prostatic, but not epididymal, cytosol a low level of progesterone binding was observed and was masked by triamcinolone acetonide. When expressed in terms of tissue DNA, cytosol androgen receptor level in the prostate only was elevated in the breeding season. Prostatic tissue showed a low level of 5 alpha-reductase in vitro which was not influenced by season. However, both tissues showed a high concentration of 5 alpha-dihydrotestosterone and in the prostate, where seasonal effects were measured, the concentration was higher in the breeding season. This indicates that although 5 alpha-dihydrotestosterone is the likely active androgen in the prostate it may be formed elsewhere. Part of the explanation for the increased growth of the prostate in the breeding season appears to be a change in receptor concentration coupled with elevated tissue androgen level.
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PMID:Some effects of breeding season and castration on the prostate and epididymis of the brushtail possum, Trichosurus vulpecula. 241 13

Previous results obtained with a model system of human epididymal tubules maintained in organ culture suggested that androgenic stimulation of this tissue resulted in responses similar to those obtained in epididymides of experimental animals under physiological conditions, as well as in other human androgen-dependent tissues. In this instance we have explored the possible influence of androgens on the activity of the androgen-converting enzymes 5 alpha-reductase and 17 beta-dehydrogenase. Activity of the former enzyme increases significantly during the culture period but no differences were found among the cultured groups, regardless of the addition of androgen. On the other hand, the activity of 17 beta-dehydrogenase was unchanged in all the experimental conditions tested. The co-culture of the tissue with explants of human testis was without effect. More than 85% of the activity of both enzymes was found localized in a fraction enriched in epithelial cells. Histological observation of the cultured tissues showed a marked disorganization of the pseudostratified epithelium in the absence of androgen while the inclusion of DHT in the media partially prevented these changes. We conclude that, under the conditions employed in these experiments, the activity of the enzymes studied is not influenced by androgens.
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PMID:The effect of in vitro androgen stimulation upon androgen metabolism and trophic parameters in cultured human epididymis. 254 Jun 81

To provide insight into the role of 5 alpha-dihydrotestosterone (DHT) in postnatal androgen physiology, we administered the 5 alpha-reductase inhibitor finasteride to male rats from birth through the onset of puberty. In 4-week-old control rats serum testosterone levels averaged 0.21 ng/ml, and DHT levels averaged 0.64 ng/ml. By 7 weeks of age, testosterone levels increased more than 7-fold to 1.57 ng/ml, while the circulating DHT level declined to 0.26 ng/ml. In both the 4- and 7-week-old inhibitor-treated animals, circulating DHT levels were 25-50% of control values, and circulating testosterone levels were higher than control values. In 7-week-old inhibitor-treated rats, the weights of prostate, penis, seminal vesicles, and epididymal tissues were only 30-50% those of the controls. However, DHT formation is apparently not critical for postnatal development of the preputial glands or the androgen-dependent perineal muscles, since the weights of these tissues were not affected by treatment with inhibitor. Treatment with the 5 alpha-reductase inhibitor had no apparent effect on testicular histology or daily sperm production despite the fact that testicular DHT content was lower (70%) and testosterone content was higher (250%) than those in controls. We conclude that DHT formation is important for the normal postnatal growth of the prostate, seminal vesicles, epididymis, and penis and may be important for normal feedback control of testosterone production in rats, but that its formation is not critical for the onset of spermatogenesis or the development of the preputial glands or the androgen-dependent perineal muscles.
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PMID:The effect of a 5 alpha-reductase inhibitor on androgen physiology in the immature male rat. 255 51

Previous experiments with inbred mice showed that chronic ethanol treatment delays male pubertal development. An initial event in sexual maturation in the rat is a transient increase in 5 alpha-reductase. The present study was conducted to determine whether similar ethanol effects occur in outbred mice (Swiss-Webster), to determine the ontological profile of testicular 5 alpha-reductase in the mouse, and to evaluate the effect of ethanol treatment on this enzyme. After 29 days of treatment with a liquid diet (beginning at age 20 days), reductions in the ethanol-treated mice as compared with the controls were noted in testicular weight (55.0 +/- 2.0 vs. 63.0 +/- 2.4 mg; P less than 0.01), epididymal sperm content (6.8 X 10(5) vs. 14.4 X 10(5); P less than 0.05), and sperm motility (45% vs. 57%; P less than 0.05). After 43 days, differences no longer existed. In chow-fed mice, a substantial rise in 5 alpha-reductase (1 unit = 1 pmole DHT formed/45 min/mg testis) began at age 24 days. Activity peaked at approximately 65 units at 25 to 30 days and gradually declined to 6.4 +/- 0.8 units at 63 days. After 29 days treatment, 5 alpha-reductase of the pair-fed control group was 26.8 +/- 4.9 units, which decreased to a baseline value of 7.0 +/- 2.1 units after 43 days treatment. In contrast, 5 alpha-reductase of the ethanol-treated group remained at baseline levels after 29 days (7.7 +/- 2.3 units) and 43 days of treatment (7.6 +/- 2.3 units).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic ethanol ingestion during puberty alters the transient increase in testicular 5 alpha-reductase in the Swiss-Webster mouse. 270 22

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 reliable isocratic high performance liquid chromatography (HPLC) procedure has been developed for the separation and subsequent radiometric quantitation of delta 4-3-ketosteroid-5 alpha-oxidoreductase enzyme activity. The specificity of this HPLC procedure has been confirmed through the use of authentic androgen radioisotopes, linearity of detector response, and mass spectral analysis. In conjunction with this we have also developed a simple Sep-Pak sample preparation procedure which allows the uniform complete isolation of these androgens from epididymal tissue homogenates. Utilizing these procedures we have determined the regional distribution of 5 alpha - reductase in the epididymis of the CD-1 mouse. Regional differences in enzyme activity were found between the caput-corpus and cauda regions. Enzyme activity (specific activity) was higher in the caput-corpus region (28.98 pmol 5 alpha - reduced androgens formed/h/mg protein) than the cauda region (6.20 pmol 5 alpha - reduced androgens formed/h/mg protein).
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PMID:Radiometric quantitation of delta 4-3-ketosteroid-5 alpha-oxidoreductase utilizing high performance liquid chromatography. 325 24


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