UNIPROT:Q8NEX9 - FACTA Search

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Query: UNIPROT:Q8NEX9 (reductase)
26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neonatal imprinting of ethylmorphine demethylase and corticosteroid 5 alpha-reductase was studied. Males, castrated at birth (day 1), were injected (sc) with testosterone, dihydrotestosterone, or estradiol on days 2, 4, and 6 and with testosterone (2 mg/rat/day) on days 50-59. Microsomes were prepared on day 60. All three steroids, at greater than or equal to 0.73 mumol/pup, increased the apparent Vmax and decreased the apparent Km of the demethylase to values that did not differ (p less than 0.05) from those of intact adult males. Analogously, all steroids, at greater than or equal to 0.73 mumol/pup, decreased the apparent Vmax of the reductase to intact male values; its apparent Km was increased to adult male values by both androgens (at greater than or equal to 0.37 mumol/pup) and by estradiol (at greater than or equal to 0.73 mumol/pup). Flutamide (1.45 mumol/pup) failed to alter these effects indicating that androgen receptors are not involved in the imprinting process. Nafoxidine (1.45 mumol/pup) blocked the effects of all three steroids, indicating that androgens and estrogens both imprint via the estrogen receptor. An inhibitor of androgen aromatase, 1,4,6-androstatriene-3, 17 dione, blocked the imprinting effects of testosterone, but not those of dihydrotestosterone. Thus, testosterone is oxidized to estradiol prior to imprinting, while dihydrotestosterone imprints as the parent compound. The latter may reflect a pharmacologic occupancy of the estrogen receptor by dihydrotestosterone.
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PMID:Neonatal programming of ethylmorphine demethylase and corticosteroid 5 alpha-reductase by testosterone, dihydrotestosterone, and estradiol. Effects of an anti-estrogen, an anti-androgen, and an inhibitor of estrogen synthetase. 289 62

Testosterone (T) triggers aggressive behavior in males of many vertebrate species; however, the neural and hormonal basis of individual differences in the frequency or intensity of aggressive behavior is still debated. Using the Japanese quail (Coturnix coturnix japonica), a species in which individuals exhibit a wide range of aggressiveness in nature and the laboratory, together with a newly devised test procedure for quantifying aggressiveness, we recently demonstrated that aggression is estrogen dependent. Here we extend these studies by testing the hypothesis that aromatization in brain is a rate-limiting step in the expression of individual differences in aggressiveness. Using procedures previously validated for this species, aromatase and 5 alpha- and 5 beta-reductase activities were estimated in selected brain regions of reproductively active male quail by measuring conversion of [3H]androstenedione to [3H]estrone, [3H]5 alpha-androstanedione, and [3H]5 beta-androstanedione, respectively. In Exp 1, behaviorally inexperienced test birds were killed 90 sec after a single behavioral test. Aggressiveness of individuals in this group, as determined by pecking and locomotor activity in response to visualization of a conspecific, ranged 3- to 4-fold from high to low. Aromatase activity in the posterior hypothalamus (PHYP) was significantly higher in males rated high for aggressiveness than in animals rated low (1.04 vs. 0.59 pmol/h.mg protein; P less than 0.02). Similar differences were observed in the anterior hypothalamus/preoptic area (AHPOA) but were not significant. In Exp 2, sexually mature males were behaviorally tested eight times over 22 days and killed 24 h after the final test. Aggressiveness varied 5-fold from high to low, although the rating in a given bird remained constant with time and repeat testing. Aromatase activity in the AHPOA was significantly greater in birds rated high for aggressiveness than in low aggressiveness birds (3.77 vs. 2.80 pmol/h.mg protein; P less than 0.02). In addition, when AHPOA aromatase in all birds was plotted against behavioral intensity, there was a 2-fold variation and a significant positive correlation (r = 0.556; P less than 0.02). Similar differences were observed in PHYP, but these were of borderline significance. By contrast, aromatase levels outside the AHPOA and PHYP were unrelated to behavior. Moreover, in both Exp 1 and 2, 5 alpha- and 5 beta-reductase activities in AHPOA, PHYP, and other brain regions; plasma T, 5 alpha-dihydrotestosterone, and total estrogens; and relative testicular weights were not consistently related to aggression.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Aromatase activity in quail brain: correlation with aggressiveness. 290 76

To elucidate the metabolic fate and possible role of androgens and their derivatives during primate fetal development, aromatase (AROM), 5 alpha-reductase (5 alpha R), and androgen receptor (AR; cytosolic) levels were assessed in the brain, heart (HRT), lung (LNG), and skeletal muscle (MUS) of fetal rhesus monkeys. Analyses were performed on tissues taken on days 100 and 160 postconception. Five male and four or five female fetuses were examined at each stage. Brain tissues analyzed included medial basal hypothalamus (MBH), amygdala (AMG), cerebellum (CB), corpus callosum (CAL; splenial region), cerebral cortex (CTX), and cingulate cortex (CNG). In the following, enzyme activities are reported as picomoles per mg protein/h, while receptor levels are femtomoles per mg protein. 5 alpha R activity was measurable in all tissues. Analysis of variance revealed significant tissue differences [P less than 0.001, combined stages and sexes; CAL (2.05) greater than MBH (1.08) greater than AMG (0.63) greater than CB (0.4)-CNG-CTX-LNG-HRT-MUS (0.02); -indicates not significantly different]. A significant age x tissue interaction (P less than 0.001) was noted which could be explained by higher MBH and CAL levels in older vs. younger fetuses and higher AMG levels in younger vs. older fetuses. There was also a significant sex x tissue interaction which was attributed to higher female values in the MBH and CAL. AROM activity was detected in all tissues. Levels varied significantly among tissues [P less than 0.001, combined stages and sexes; MBH (0.80)-AMG (0.76) greater than CAL (0.4)-CNG-CB-CTX-LNG-HRT-MUS (0.07)]. Significant age (P less than 0.001) and age x tissue (P less than 0.001) effects were noted, which were due to higher MBH and AMG levels in younger vs. older fetuses. No sex difference in AROM levels was evident in any tissue. AR was measurable in all cases. Although stage and sex differences were not significant, tissue levels varied significantly [P less than 0.001; LNG (2.8)-MUS (2.6)-MBH (2.2) greater than HRT-AMG-CB-CTX-CAL-CNG (0.9)]. These findings indicate that neural and nonneural fetal primate tissues have the potential for transforming androgens to products that could have greater or lesser biological activity. AR were also noted through which dihydrotestosterone or testosterone could effect a genomic response. Since stage, tissue, and sex differences were evident in neural tissues, metabolic and receptor activities may be important for the normal differentiation of sexually dimorphic behavioral systems in monkeys as well as for potential teratogenic changes under abnormal metabolic or physiological conditions.
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PMID:5 alpha-reductase, aromatase, and androgen receptor levels in the monkey brain during fetal development. 291 90

5 alpha-Reductase and aromatase activities were measured in fetal and newborn rat gubernaculum and other tissues by radiometric assays using [1 beta-3H]testosterone as substrate. Aromatase activity was measured by the stereospecific release of tritium into the incubation medium, and 5 alpha-reductase was assessed by measuring the amount of 5 alpha-reduced steroids produced during the same incubations. Aromatase activity was low (less than 0.2 pmol/h.mg protein) in gubernaculum at all ages studied, whereas the activity in postnatal ovary ranged from 3.9-20 pmol/h.mg protein. 5 alpha-Reductase activity was relatively high in day 18 fetal gubernaculum (approximately 115 pmol/h.mg protein), but 2 days later in development (fetal day 20), 5 alpha-reductase activity had declined to approximately 21 pmol/h.mg protein. 5 alpha-Reductase activity was very low (less than 10 pmol/h.mg protein) in the postnatal gubernaculum. Histological examination of day 18 fetal gubernaculum indicated that it is composed of dense, poorly organized, mesenchymal tissue. By day 20 of gestational development, primitive muscle cells are recognizable in the periphery of the gubernaculum, and by day 3 of postnatal development the gubernaculum is composed almost entirely of muscle. These findings suggest that 5 alpha-reductase activity may be located in the mesenchymal cells and may be important in early differentiation of the gubernaculum in the male. The administration of a 5 alpha-reductase inhibitor to pregnant rats from days 14-22 of gestation inhibited the normal growth rate of the gubernaculum, as assessed by measuring the protein content of the gubernaculum in control and treated rats, but did not have any profound effect on the histological development of the gubernaculum.
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PMID:Developmental pattern of 5 alpha-reductase activity in the rat gubernaculum. 291 97

The effects of antioestrogens, antiandrogens and of various inhibitors of testosterone metabolism on testosterone metabolism in the quail hypothalamus and cloacal gland were studied by an in-vitro radioenzymatic assay. It was found that antioestrogens and antiandrogens generally had little or no effect on aromatase and 5 alpha- and 5 beta-reductases of testosterone, except when used at very high doses. The 5 alpha-reductase inhibitor, 17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one, inhibited both 5 alpha- and 5 beta-dihydrotestosterone production without markedly affecting aromatase activity. Surprisingly, the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione, inhibited not only the production of oestradiol but also that of 5 beta-dihydrotestosterone and, to a lesser extent, 5 alpha-dihydrotestosterone. These unexpected properties should be taken into account when interpreting the results of in-vivo experiments using these compounds.
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PMID:Inhibition of testosterone metabolism in the brain and cloacal gland of the quail by specific inhibitors and antihormones. 295 Jan 96

The relative contribution of androgenic and estrogenic metabolites of testosterone to the activation of sexual behavior was studied in Japanese quail by using inhibitors of testosterone metabolism, antiestrogens and antiandrogens. These compounds were tested in castrated birds whose sexual behavior had been activated by silastic implants of testosterone (T) or daily injections of testosterone propionate (TP) or diethylstilboestrol (DES). The aromatase inhibitor ATD only depressed T-induced behavior when injected at high doses and the 5 alpha-reductase inhibitor, 4MA was inactive in this respect. The antiestrogens, tamoxifen (TAM) and nitromifene citrate (CI-628) strongly depressed sexual behavior but they also drastically reduced the crowing behavior which is typically androgen-dependent which throws some doubts on the specificity of their action. The antiandrogens, flutamide and cyproterone acetate (CA), only had limited inhibitory effects on the copulatory behavior but similarly decreased only marginally the crowing. As they strongly depressed the cloacal gland growth, it can be ascertained that they were injected in sufficient amounts and their lack of action on crowing questions the ability of these compounds to inhibit brain processes even when they are androgen-dependent. Taken together with the results of previous experiments which tested the behavioral effects of the testosterone metabolites, the present data confirm the implication of both androgenic and estrogenic metabolites of testosterone in the activation of behavior. Their interaction remains, however, poorly defined and its understanding will probably require the identification of the biochemical processes which in the brain mediate the behavior.
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PMID:Effects of metabolism inhibitors, antiestrogens and antiandrogens on the androgen and estrogen induced sexual behavior in Japanese quail. 295 May 30

Dehydroepiandrosterone sulfate (DHEAS) determination in biological fluids was carried out by enzymatic hydrolysis and conversion into estrogens [estrone (E1) and estradiol (E2)] by the multienzyme system of human placental microsomes. The enzymatic complex consists of sulfatase, 3 beta-hydroxysteroid oxido reductase and 5en----4en isomerase which converts DHEAS into androstenedione (A); the latter component is further converted into estrogens by the aromatase. The resulting estrogens were determined from the NADH formed by the transhydrogenation reactions of human placental dehydrogenase. NADH was measured by bioluminescence. As little as 4 pg was assayable by this rapid enzymatic method, with a coefficient of variation of 8%. The results are in good agreement with radioimmunoassay and the method is suitable for routine use.
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PMID:Bioluminescence: an improvement in the enzymatic assay of dehydroepiandrosterone sulfate in biological fluids. 295 62

In addition to the histology of epithelial and stromal elements of prostates from intact dogs (group 0) and castrated dogs (group I), the latter of which were treated with androstenedione (group II), androstenedione plus the aromatase inhibitor 1-methyl-1,4-androstadiene-3,17-dione (group III), or androstenedione plus aromatase inhibitor and cyproterone acetate (group IV) (Habenicht and El Etreby: The Prostate 11:133-143, 1987) it was of interest to study the influence of such in vivo treatment on the prostatic 5 alpha-reductase, which is responsible for the cellular conversion of testosterone to 5 alpha-dihydrotestosterone. Michaelis constants (KM) and maximal activities (Vmax) of 5 alpha-reductase were determined under optimized incubation conditions in mechanically separated epithelium and stroma. The metabolites were separated by high-performance liquid chromatography and determined radiometrically. The main results were: 1) The mean KM (nM +/- SEM) was significantly (P less than .001) higher in epithelium (892 +/- 132) than stroma (70 +/- 11). The same was true concerning the Vmax (pmol.mg protein-1.h-1 +/- SEM) in epithelium (54.6 +/- 5.8) as compared to stroma (13.0 +/- 2.0). 2) No specific in vivo or in vitro effect of the aromatase inhibitor on the KM and Vmax data was found. 3) In prostates of intact dogs and dogs of group II the proportion of epithelial 5 alpha-reductase exceeded distinctly that of stromal 5 alpha-reductase. 4) In groups I, III, and IV the proportion of epithelial 5 alpha-reductase was rather low. These data were discussed in the light of the histological findings.
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PMID:5 alpha-reductase activity in epithelium and stroma of prostates from intact and castrated dogs treated with androstenedione, the aromatase inhibitor 1-methyl-1,4-androstadiene-3,17-dione, and cyproterone acetate. 296 68

Aromatase is an enzyme complex that is composed of a specific form of cytochrome P-450 and a flavoprotein, NADPH-cytochrome P-450 reductase. Aromatase activity of granulosa cells is increased markedly by follicle-stimulating hormone (FSH) and by analogs of cyclic AMP. It was the objective of the present study to investigate the effects of FSH and dibutyryl cyclic AMP (Bt2cAMP) on the synthesis of NADPH-cytochrome P-450 reductase in rat granulosa cells maintained in vitro. Granulosa cells were obtained from the ovaries of diethylstilbestrol (DES)-treated immature rats and were incubated in the presence of DES (10(-7) M), DES + FSH (250 ng/ml), or DES + Bt2cAMP (1 mM) for up to 72 h. After 72 h of incubation, aromatase activity of cells incubated with DES alone was 5 pmoles estrogen formed 2 h-1 mg-1 protein and was increased greater than 60-fold in cells incubated with FSH or Bt2cAMP. NADPH-cytochrome P-450 reductase was immunoisolated from [35S]methionine-labeled lysates of granulosa cells incubated for 72 h in the absence or presence of stimulatory factors. The rate of synthesis of reductase was found to be increased about 3-fold in cells incubated with DES + FSH or DES + Bt2cAMP as compared to cells incubated with DES alone. By immunoblot analysis we found that the cellular content of reductase was increased about 2-fold by FSH and Bt2cAMP treatment. Reductase specific activity was 10 nmoles min-1 mg-1 protein in membrane fractions of DES-treated cells and was increased 1.6-fold by FSH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of aromatase activity of rat granulosa cells: induction of synthesis of NADPH-cytochrome P-450 reductase by FSH and dibutyryl cyclic AMP. 298 33

Using human adipose stromal cells in monolayer culture as a model system for study of the regulation of aromatase activity, as well as polyclonal antibodies raised in this laboratory against aromatase cytochrome P-450 (cytochrome P-450AROM), it was found that the rate of synthesis of cytochrome P-450AROM was stimulated by dibutyryl cyclic AMP. This stimulation was attenuated by epidermal growth factor and was potentiated by phorbol esters. These changes in cytochrome P-450AROM synthesis were associated with comparable changes in the levels of translatable cytochrome P-450AROM mRNA, as well as with changes in the activity of aromatase of these cells. By contrast, there was little change in the synthesis of the reductase component of the aromatase enzyme complex in response to these factors. The increase in mRNA was blocked by cycloheximide, indicative of a requirement for protein synthesis in mediating this inductive response. It is concluded that aromatase activity is regulated primarily by changes in the level of mRNA encoding cytochrome P-450AROM, and that such changes are likely a reflection of changes in the rate of transcription of the gene encoding this enzyme. Increases in the levels of cytochrome P-450AROM mRNA are apparently mediated by a regulatory protein(s), similar to that found for other steroidogenic forms of cytochrome P-450.
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PMID:Regulation of estrogen biosynthesis in human adipose stromal cells. Effects of dibutyryl cyclic AMP, epidermal growth factor, and phorbol esters on the synthesis of aromatase cytochrome P-450. 303 80

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