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)

Two siblings with 46,XY male pseudohermapthroditism were demonstrated to have the phenotype characteristic of 5 alpha-reductase deficiency, namely normal testes and male Wolffian duct derivatives (epididymis, vas deferens, and seminal vesicle) terminating in a blind-ending vagina. Clitoromegaly was present at birth and increased further at the time of expected puberty. The diagnosis of 5 alpha-reductase deficiency was confirmed by demonstration of male levels of testosterone and testosterone precursors before and after hCG administration, elevated plasma testosterone to dihydrotestosterone and urinary etiocholanolone to androsterone ratios, and by in vitro studies indicating 5 alpha-reductase enzyme deficiency in the epididymis of one patient. Studies of control and mutant epididymal microsomes indicated that a single enzyme is responsible in the normal person for the 5 alpha-reduction of testosterone and cortisol (and probably other delta 4-3-ketosteroids as well) and that 5 alpha-reductase activity is undetectable for all substrates examined in the mutant. This finding explains why the formation of 5 alpha-reduced glucocorticoids is also defective in the disorder.
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PMID:Clinical, endocrinological, and enzymatic characterization of two patients with 5 alpha-reductase deficiency: evidence that a single enzyme is responsible for the 5 alpha-reduction of cortisol and testosterone. 26 18

The effects of unilateral orchidectomy on the adult rat epidiymal testosterone metabolizing enzymes, delta 4-5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase, are investigated. Five weeks following unilateral orchidectomy, it is found that the activity of 3 alpha-hydroxysteroid dehydrogenase per organ is not altered, whereas delta 4-5 alpha-reductase activity decreased by more than 80% on the side of the orchidectomy. Neither accessory sex tissue weights, ventral prostate and seminal vesicles, nor the concentration of circulating testosterone, luteinizing hormone, follicle-stimulating hormone, or prolactin is altered by unilateral orchidectomy. These data indicate that (1) epididymal 3 alpha-hydroxysteroid dehydrogenase activity can be maintained by circulating androgens and that (2) the major factor regulating delta 4-5 alpha-reductase activity is not a substance secreted by the testes into the peripheral circulation. It is suggested that a substance directly secreted into the epididymis by the testis regulates epididymal delta 4-5 alpha-reductase activity.
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PMID:Effects of unilateral orchidectomy on rat epididymal delta 4-5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase. 51 41

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

The epididymal epithelial ultrastructure has been described in the adult male North American opossum, Didelphis virginiana. Morphological results have suggested that absorptive activity is prominent in the proximal epididymal region by virtue of numerous microvilli, an endocytotic complex, dense granules, and multivesicular bodies in the apical cytoplasm. In contrast, the middle and distal epididymal regions exhibit ultrastructural features indicative of protein synthesis such as large invaginated euchromatic nuclei, large nucleoli, and increased amounts of granular endoplasmic reticulum. It is in the middle and distal epididymal regions where sperm head rotation and sperm pairing take place. Epididymal delta 4-3-ketosteroid-5 alpha-oxidoreductase (5 alpha-reductase) activity also has been measured. It has been found that the level of enzyme activity differs significantly (p less than 0.01) between the proximal, middle, and distal epididymal regions. Enzyme-specific activity has been found to be highest in the middle region (47.6 +/- 5.4 picomoles 5 alpha-reduced androgens formed/b/mg protein), lower in the distal region (18.3 +/- 0.7 picomoles 5 alpha-reduced androgens formed/b/mg protein), with little activity (2.4 +/- 1.2 picomoles 5 alpha-reduced androgens formed/h/mg protein) found in the proximal epididymal region. This regional distribution of enzyme activity differs markedly from that reported for eutherian mammals. Both the suggested epididymal protein synthetic and secretory activity and the level of epididymal 5 alpha-reductase activity appear to correlate regionally with the morphological changes that occur in the opossum spermatozoa as they transit the epididymis.
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PMID:Unique regional distribution of delta 4-3-ketosteroid-5 alpha-oxidoreductase and associated epididymal morphology in the marsupial, Didelphis virginiana. 367 95

During our studies on the active moiety of parotin, we succeeded in purifying MP-parotin (MW = 130000) and parotin-subunit (MW = 45000) from crude parotin. Furthermore, AA-1 (MW = 9100) was isolated after the tryptic cleavage of the parotin-subunit. AA-1 was the smallest unit ever obtained which had serum Ca-decreasing activity and circulating leucocyte-increasing activity together with the nature of specific localization in bone. Therefore, AA-1 was considered to contain the essential residues for parotin activity in its structure. Since crude parotin was also known to show andromimetic action, these parotin components reduced in size were assayed in this regard. A daily injection of MP-parotin (500 micrograms/kg), parotin-subunit (20 micrograms/kg) or AA-1 (20 micrograms/kg) was administered subcutaneously for two weeks to male rats weighing 200 approximately 220 g. The dynamics of the testicular biosynthesis of testosterone from 3H-pregnenolone and 14C-progesterone via delta 4, delta 5-pathway and the transition of delta 5 to delta 4-steroids were measured. MP-parotin and the parotin-subunit stimulated the pathway of pregnenolone----17-hydroxypregnenolone----dehydroepiandrosterone---- androstenedione----testosterone and resulted in the elevation of serum testosterone levels. Cyclic AMP levels in the testicular homogenate and the motility of epididymal sperm were also increased by the treatment. On the other hand, AA-1 showed no effect on these parameters. It was concluded that andromimetic activity, which is involved in MP-parotin or parotin subunit was independent of parotin activity on the bone tissue.
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PMID:[The effects of parotin components on testosterone biosynthesis in rats]. 632 59

The curve of the specific activity of rat epididymal nuclear delta 4-5 alpha-reductase is bell shaped as a function of age, whereas that of cytoplasmic 3 alpha-hydroxysteroid dehydrogenase does not change significantly with age. The present study examines the subcellular distribution of delta 4-5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase in the caput-corpus and cauda epididymidis during development. A 5-step discontinuous sucrose gradient was developed for fractionation of epididymal homogenates. By using enzyme markers specific for different subcellular organelles, the five different subcellular fractions obtained were shown to be of cytoplasmic, microsomal, mitochondrial, nuclear and spermatozoal origin. 3 alpha-Hydroxysteroid dehydrogenase activity was associated only with the cytoplasmic fraction. The activity of the enzyme did not change significantly with age in either the caput-corpus or cauda epididymidis. delta 4-5 alpha-Reductase activity was found in fractions containing microsomal and nuclear markers. delta 4-5 alpha-Reductase activity in the nuclear fraction of the caput-corpus epididymidis was evident in the youngest age group (Day 25), increased 4-fold and peaked in the next age group (Day 35), and declined with each successive age group: Day 45 (60% of maximum), Day 60 (20% of maximum), Day 75 (15% of maximum) and Day 105 (10% of maximum). In contrast, microsomal delta 4-5 alpha-reductase activity increased successively from Day 25 to Day 105; enzyme activity doubled between these two ages. The ratio of nuclear to microsomal delta 4-5 alpha-reductase activity from the caput-corpus epididymidis thus changed markedly with age: Day 25:1.32; Day 35:3.76; Day 45:2.44; Day 60:1.03; Day 75:0.41; and Day 105:0.21. In the cauda epididymidis nuclear delta 4-5 alpha-reductase activity was only evident at Day 35 and Day 45; in microsomal fractions, activity was first found at Day 35 and did not subsequently change with age. These results demonstrate that: 1) epididymal 3 alpha-hydroxysteroid dehydrogenase activity is found only in the cytoplasmic fraction; 2) delta 4-5 alpha-reductase activity is found in nuclear and microsomal fractions; and 3) the subcellular distribution of delta 4-5 alpha-reductase activity changes markedly with age and epididymal section, suggesting differential regulation of nuclear and microsomal delta 4-5 alpha-reductase activities.
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PMID:Subcellular distribution of steroid delta 4-5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase in the rat epididymis during sexual maturation. 657 16

Epididymal delta 4-steroid 5 alpha-reductase (cholestenone 5 alpha-reductase), the enzyme that catalyses the conversion of testosterone into the biologically active metabolite dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one), is a membrane-bound enzyme found in both nuclear and microsomal subcellular fractions. In order to characterize epididymal delta 4-steroid 5 alpha-reductase, it was first necessary to solubilize the enzymic activity. Of the various treatments tested, a combination of 0.5% (w/v) Lubrol WX, 0.1 M-sodium citrate and 0.1 M-KCl maintained enzymic activity at control values and solubilized 66% of total epididymal delta 4-steroid 5 alpha-reductase activity in an active and stable form. The sedimentation coefficient of solubilized delta 4-steroid 5 alpha-reductase, as determined in continuous sucrose density gradients, was greater for the microsomal than for the nuclear enzyme (11.6S compared with 10.1S). Although the apparent Km values of the enzyme for testosterone were similar in nuclear and microsomal subcellular fractions (range 1.75 x 10(-7) - 4.52 x 10(-7)M), the apparent Km of the enzyme for NADPH was about 30-fold greater for the microsomal enzyme than for the nuclear enzyme. The apparent Km of the enzyme for either substrate was not significantly altered after solubilization. The relative capacity of steroids to inhibit the enzymic activity, the pH optima and the effects of Ca2+ and Mg2+ were similar for membrane-bound and solubilized delta 4-steroid 5 alpha-reductase in both the nuclear and the microsomal fractions. The results reported demonstrate that epididymal delta 4-steroid 5 alpha-reductase can be solubilized in an active and stable form with no significant changes in the kinetic characteristics of the enzyme after solubilization; furthermore, kinetic and molecular-size differences observed for the nuclear and the microsomal forms of the enzyme suggest that there may exist at least two forms of epididymal delta 4-steroid 5 alpha-reductase.
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PMID:Solubilization and partial characterization of rat epididymal delta 4-steroid 5 alpha-reductase (cholestenone 5 alpha-reductase). 687 Aug 29

delta 4-5 alpha-Reductase activity is apparently regulated by a testicular factor(s) secreted directly into the epididymis, whereas 3 alpha-hydroxysteroid dehydrogenase activity, in this tissue, appears to reflect circulating androgen levels. To test whether the factor(s) regulating delta 4-5 alpha-reductase activity is directly associated with spermatozoa, a developmental study was undertaken to temporally correlate various parameters of the male reproductive tract with enzymatic activities. delta 4-5 alpha-Reductase activity is first detectable at 21 days of age. Activity increases until day 77, after which time enzymatic activity decreases by more than 60%, reaching steady adult values at 105 days. 3 alpha-Hydroxysteroid dehydrogenase activity is detectable as early as 7 days. Levels of this enzyme increase until day 63, after which time constant adult values are maintained until at least 1 yr. Spermatids and/or spermatozoa are first seen in the testes at 42 days, and plateau levels are reached by day 77. Spermatozoa are first seen in the epididymis at 49 days and reach maximal values by 91 days; no significant change occurs thereafter (until 365 days). Increases in seminal vesicle and ventral prostate weights are of a sigmoidal type, paralleling increases in plasma androgens, with the greatest rate of rise between days 35--63. This sigmoidal type of increase in tissue weights and plasma androgens is similar to that seen for epididymal 3 alpha-hydroxysteroid dehydrogenase but markedly different from that found for delta 4-5 alpha-reductase. The importance of delta 4-5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase activities in the epididymis before the entry of spermatozoa and the decline in delta 4-5 alpha-reductase activity with age is discussed.
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PMID:Steroid delta 4-5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase in the rat epididymis during development. 693 15

When [4-14C]-5 alpha-dihydrotestosterone was incubated with the homogenate of human epididymis, 5 alpha-androstane-3 alpha, 17 beta-diol and 5 alpha-androstane-3 beta, 17 beta-diol were identified as major metabolites. The ratio of 3 alpha- to 3 beta-epimer in androstanediol formation was approximately 2.4. 5 alpha-Androstane-3, 17-dione was also identified as a minor metabolite. Among the subcellular fractions, both the human epididymal 3 alpha- and 3 beta-hydroxysteroid dehydrogenases were localized almost exclusively in the cytosol fraction (105,000 X g supernatant). Both enzymes had optimum pH at 7.5 and optimum temperature at 46 degrees C. NADPH was a more preferable cofactor than NADH for both dehydrogenases. The Michaelis constants (Km) of 3 alpha- and 3 beta-hydroxysteroid dehydrogenase for 5 alpha-dihydrotestosterone were similar and estimated as 8 X 10(-5) M, but the enzymes were unsaturable with the substrate under the conditions investigated, indicating low affinity and high capacity of both dehydrogenases for 5 alpha-dihydrotestosterone. The human epididymal 5 alpha-reductase revealed a regional difference in activity. The 5 alpha-reductase activity in the most proximal part of the head (ductuli efferentes) was one seventh to one tenth the activity in the remaining part of the epididymis which was constructed of ductus epididymis. Except for this finding, the activity of 5 alpha-reductase was highest in the head, then declined along the course to the tail portion. The 5 alpha-reductase for testosterone was competitively inhibited by delta 4-3-oxosteroids such as progesterone, 20 alpha-dihydroprogesterone, 17 alpha-hydroxyprogesterone, 4-androstenedione, 11-deoxycorticosterone, corticosterone and 11-deoxycortisol, which had inhibition constants (Ki) of 3.3 X 10(-9) M, 2.2 X 10(-9) M, 1.8 X 10(-8) M, 1.3 X 10(-8) M, 8.3 X 10(-9) M, 1.5 X 10(-7) M and 8.7 X 10(-8) M, respectively, suggesting the possibility that the 5 alpha-reduction of testosterone is regulated by other delta 4-3-oxosteroids.
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PMID:Studies on the human epididymis: partial characterization of 3 alpha- and 3 beta-hydroxysteroid dehydrogenase, regional distribution of 5 alpha-reductase and inhibitory effect of 4 delta-3-oxosteroids on 5 alpha-reductase. 696 21

Concentrations of testosterone, progesterone, Delta4-androstenedione, dihydrotestosterone, 11-ketotestosterone, estrone, estradiol-17beta, 5alpha-androstane, 3alpha, 17beta-diol, and 17alpha-hydroxy, 20beta-dihydroprogesterone were determined by radioimmunoassays in the blood plasma and testicular homogenates of Scyliorhinus canicula. Samples were collected almost every month for 27 months. The weights and sizes of reproductive organs and sperm reserves were also measured over the same period. Quantitatively, testosterone was the principal steroid present. Testicular and epididymal weights, sperm reserves, and clasper size varied throughout the year, but not always in a synchronous fashion. Most of the testicular steroids had an annual peak, generally in February, except for progesterone. The plasma concentrations of progesterone, Delta4-androstenedione, and androgens presented various degrees of fluctuation over the year, but were not synchronized: maxima occurred during autumn-winter for androgens and progesterone, during spring for Delta4-androstenedione. Thus, various aspects of S. canicula reproductive function appear to be influenced by season, the sea temperature being, most probably, a major determinant in this respect.
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PMID:Seasonal variations in sex steroids and male sexual characteristics in Scyliorhinus canicula. 1056 58


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