Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many New World primates such as the squirrel monkey have extraordinarily high plasma levels of steroid hormones including cortisol, testosterone, progesterone and vitamin D3. While plasma estrogen levels in female squirrel monkeys apparently are approximately the same as those found in other species no information is available for males. The present results indicate that the plasma levels of estrone (E1), estradiol (E2), and E1 sulfate are approximately 10-fold higher than those found in men. Comparative in vitro studies of androgen metabolism in genital skin fibroblasts indicate that squirrel monkey cells have higher aromatase and lower 5-alpha-reductase activity than human cells. Estimation of aromatase activity in vivo by a radiometric assay indicates that the high plasma estrogens are derived by peripheral conversion from testicular and/or adrenal androgens.
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PMID:Conversion of androgens to estrogens in the male squirrel monkey (Saimiri sciureas). 350 16

Ovarian slices of the European eel at the silver stage were incubated with 4 tritiated precursors (pregnenolone, progesterone, androstenedione, testosterone) in the presence or not of an inhibitor of 11 beta-hydroxylase activity, metopirone. Ether extracts were submitted to a gradient elution chromatography on celite columns. Isolated peaks were identified by isopolarity on TLC, microchemical reactions and recrystallization to constant specific activity. Interpretation of the results shows that the ovary of the European eel contains the following enzymes: a 3 beta-hydroxysteroid dehydrogenase, 5----4-ene-isomerase complex, a 17 alpha-hydroxylase, a C21-C19 desmolase, a 17 beta-hydroxysteroid oxidoreductase, a 5 alpha-reductase, a 3 beta-hydroxysteroid oxidoreductase and an aromatase complex. Metopirone effect indicates the presence of an 11 beta-hydroxylase activity. At this stage, 5 beta-reductase, 20 beta-reductase and 21-hydroxylase activities are not detected in the ovary. Water-soluble steroids were formed from all the precursors used. It appears that the ovarian biosynthesis is orientated towards the production of 5 alpha-reduced compounds and that this might limit the production of 17 beta-estradiol by lowering the amount of disposable endogenous precursors.
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PMID:Ovarian metabolic pathways of steroid biosynthesis in the European eel (Anguilla anguilla L.) at the silver stage. 351 3

The conversion of androgens to active metabolites by neural tissue is believed to be an essential component in the cellular mechanism of androgen-induced neuroendocrine responses. In this study, we measured the in vitro aromatization and 5 alpha-reduction of androgens in incubations of microdissected brain regions from four intact and five castrated (6 weeks) adult male rhesus monkeys. Individual nuclei were microdissected from 600-microns frozen brain sections and homogenized in a potassium phosphate buffer. Aromatase activity was measured by a radiometric assay that uses the incorporation of tritium from [1 beta-3H]androstenedione into 3H2O as an index of estrogen formation. We estimated 5 alpha-reductase activity by isolating 5 alpha-dihydrotestosterone on two different chromatography systems and measuring the amount of this product formed from [1 alpha,2 alpha-3H]testosterone. We acidified a portion of each homogenate and determined LHRH content by RIA. Between brain nuclei, aromatase activity varied 1500-fold, whereas 5 alpha-reductase activity varied only 3-fold. Both enzyme activities were highest in amygdaloid, medial preoptic, and medial diencephalic nuclei and lowest in the caudate nucleus. Aromatase activities in the supraoptic nucleus, periventricular area, medial preoptic area-anterior hypothalamus, and lateral hypothalamus were significantly (P less than 0.05) lower in castrated males. Castration did not significantly affect 5 alpha-reductase activity, except for an increase in the basolateral amygdala. The highest concentrations of LHRH were in the infundibular nucleus-median eminence and were 30 times greater than amounts measured in preoptic and medial hypothalamic nuclei. The LHRH contents of the infundibular nucleus-median eminence, ventral medial nucleus, and lateral hypothalamus were significantly lower in castrated males (P less than 0.05). In addition, we observed a significant correlation between aromatase activity and LHRH content in the basal hypothalamus of intact males (r = 0.947; P less than 0.05; n = 8), but not in the preoptic-anterior hypothalamus (r = 0.068; P greater than 0.05; n = 10). No correlation was observed between 5 alpha-reductase activity and LHRH content in either area. These data indicate that castration selectively affects androgen metabolism and LHRH content in discrete regions of the brain of male monkeys and suggest that aromatase and 5 alpha-reductase are regulated differentially in the primate brain.
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PMID:Regulation of androgen metabolism and luteinizing hormone-releasing hormone content in discrete hypothalamic and limbic areas of male rhesus macaques. 353 57

The conversion of testosterone to estradiol by aromatase and to dihydrotestosterone by 5 alpha-reductase was measured in the medial basal hypothalamus of starved and control male rats. Activities of both enzymes were significantly reduced in starved animals. Aromatase activity was 18.2 +/- 2.3 versus 29.8 +/- 5.7 fmol E2/mg protein/90 min (mean +/- SEM, P less than 0.02) and 5 alpha-reductase was 4.95 +/- 0.35 versus 5.96 +/- 0.30 pmol DHT/mg protein/90 min (P less than 0.02) for starved and control animals respectively. The results indicate that hypothalamic metabolism of testosterone is decreased during starvation. Therefore the increased sensitivity of the T-LH feedback described earlier in starved rats [4] cannot be explained by changes in central testosterone metabolism.
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PMID:Testosterone metabolism in the medial basal hypothalamus of the starved male rat. 358 55

In numerous vertebrate species including Japanese quail (Coturnix coturnix japonica), actions of testosterone (T) on neuroendocrine target tissues are mediated in part by conversion to estrogenic and androgenic metabolites. In order to assess which pathways were favored in each identified androgen target area in quail brain and whether there were discernible sex differences, we developed an assay for simultaneously quantifying aromatase, 5 alpha-, and 5 beta-reductase. In addition, we made the first definitive identification of aromatase in quail pituitary and compared all three enzyme activities in the pituitary of males and females. Enzymes were measured in tissue homogenates by the conversion of [3H]androstenedione to [3H]estrone, [3H]5 alpha-androstanedione, and 5 beta-androstanedione. Aromatase activity was restricted to limbic tissues (anterior hypothalamus greater than posterior hypothalamus greater than septum greater than archistriatum containing nucleus taenia) while hyperstriatum, cerebellum, and midbrain containing nucleus intercollicularis were aromatase-negative. Quail pituitary aromatized androgen at rates equivalent to anterior hypothalamus/pre-optic area (aHPOA). 5 alpha- and 5 beta-reductase were present in all tissues tested. Aromatase was significantly higher in aHPOA and pituitary of males, whereas 5 alpha-reductase was significantly higher in female pituitary. These data suggest that a complex of androgen-metabolizing enzymes controls the neuroanatomic (spatial) distribution of active hormone in neuroendocrine tissues and that quantitative differences between males and females may account for sex differences in behavior.
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PMID:A comparison of aromatase, 5 alpha-, and 5 beta- reductase activities in the brain and pituitary of male and female quail (C. c. japonica). 361 47

We describe a very sensitive and precise assay which allows one to study the metabolism of testosterone (T) in small brain nuclei dissected out according to the method of Palkovits and Brownstein. With this method, the neuroanatomical distributions of aromatase, and 5 alpha- and 5 beta-reductase activities were studied in adult male quail (Coturnix coturnix japonica). The different enzymes show different neuroanatomical distributions. Production of estradiol-17 beta (E2) was highest in the sexually dimorphic nucleus preopticus medialis (POM). We showed previously that the preoptic aromatase activity is higher in male than in female quail. As the POM is a central and very large structure within the preoptic area, the present results suggest a relationship between the neuroanatomical and the biochemical sex differences. By contrast, the production of 5 alpha-DHT was highest in the lateral hypothalamic area (LHY), the bed nucleus of the pallial commissure (BPC) and the lateral septum (SL). The 5 beta-reductase activity was highest in the lateral septum and in the ventral part of the archistriatum (AV). Moreover, there was a rostral to caudal decrease in 5 beta-reductase activity in the hypothalamus.
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PMID:Neuroanatomical distribution of testosterone-metabolizing enzymes in the Japanese quail. 367 76

Female quail are less sensitive than males to the activating effects of testosterone (T) on behavior. Testosterone induces hypothalamic aromatase activity more efficiently in males than in females (higher Vmax but similar Km). As the conversion of T to estradiol (E2) is important for the activation of male sexual behavior, we propose that the incapacity of the female hypothalamus to produce behaviorally active E2 contributes to their insensitivity to T. The 5 alpha-reductase, which converts T into 5 alpha-dihydrotestosterone (5 alpha-DHT), is induced by T specifically in the anterior hypothalamus of both sexes.
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PMID:Testosterone-induced brain aromatase is sexually dimorphic. 370 27

Pre-incubation of monolayer cultures of human skin fibroblasts with 1,25-dihydroxycholecalciferol (1,25-D3; 0.1-10 nmol/l) increased the rate of conversion of androstenedione into oestrone (aromatase activity) when measured subsequently in the presence of a 5 alpha-reductase inhibitor (10 mumol/l). Maximal stimulation (14- to 89-fold with 10 nmol 1,25-D3/l) occurred 12 h after addition of the hormone and was maintained for up to 48 h. Stimulation was prevented by cycloheximide. In one cell line high 1,25-D3 concentrations (greater than 30 nmol/l) prevented the increase in aromatase activity; this did not appear to result from direct enzyme inhibition by 1, 25-D3. The possibility is considered that 1,25-D3 could act as a physiological regulator of peripheral aromatase. As oestrogens can prevent postmenopausal bone loss, it is speculated that 1,25-D3 might protect against bone resorption by maintaining peripheral oestrogen biosynthesis.
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PMID:1, 25-Dihydroxycholecalciferol stimulates conversion of androstenedione into oestrone by human skin fibroblasts in culture. 375 60

To study the ability of the olfactory epithelium (OE) to transform testosterone (T) into its active metabolites estradiol (E2) and dihydrotestosterone (DHT), and the influence of castration on this ability, 24 adult male rats were either castrated, and subsequently treated with oil or T, or sham operated. In all groups the in vitro conversion of T by the OE into E2 and DHT is relevant, demonstrating for the first time the presence of aromatase and of 5 alpha-reductase in this tissue. In particular conversion of T into E2 is lowered by castration and restored by T replacement, suggesting that aromatization in this tissue is androgen dependent. The ability of circulating T to influence morphological and physiological features of the OE suggests the hypothesis that androgens may vary the functioning of the olfactory apparatus and modulate the efficiency by which olfactory information is conveyed to the brain.
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PMID:Testosterone metabolism in the olfactory epithelium of intact and castrated male rats. 376 55

The present study reports the effects exerted by 1,4,6-androstatriene-3,17-dione (ATD), 4-hydroxy-4-androstene-3,17-dione (4-OH-A) and 4-acetoxy-4-androstene-3,17-dione (4-Ac-A), three steroids known to inhibit the aromatization of androgens to estrogens, on the in vitro metabolism of labelled testosterone (T), dihydrotestosterone (DHT) and androstenedione (delta-4-A) in the ventral prostate of adult male rats. It has been found that ATD, in the concentration tested, does not influence the conversion of labelled T into DHT, but decreases the formation of 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol (diols). On the contrary, 4-OH-A and 4-Ac-A simultaneously decrease the formation of DHT and the diols. When T is used as the substrate, the presence in the medium of these three steroids enhances the formation of delta-4-A and of 5 alpha-androstanedione (5 alpha-A). ATD, but not 4-OH-A and 4-Ac-A inhibits the conversion of labelled DHT into the diols. The transformation of labelled delta-4-A into 5 alpha-A is not modified by either ATD or 4-OH-A, while 4-Ac-A exerts only a small inhibition. These results suggest that the three aromatase inhibitors tested are able to profoundly modify the metabolism of T in the ventral prostate of the rat. In particular: 4-OH-A and 4-Ac-A are able to inhibit the conversion of T into DHT; ATD is able to inhibit the conversion of DHT into the diols; ATD and 4-OH-A do not inhibit the process of 5 alpha-reduction of delta-4-A into 5 alpha-A, while 4-Ac-A exerts only a minor effect. It is suggested that in the ventral prostate of the rat there are two different 5 alpha-reductase isoenzymes, one sensitive to the inhibitory effect of the steroid tested and which is responsible for the conversion of T into the 5 alpha-reduced metabolites of the 17-OH series (DHT and the diols), and a second one, insensitive to the effects of the three steroids, which affects the conversion of delta-4-A into 5 alpha-A.
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PMID:Effect of 1,4,6-androstatriene-3,17-dione (ATD), 4-hydroxy-4-androstene-3,17-dione (4-OH-A) and 4-acetoxy-4-androstene-3,17-dione (4-Ac-A) on the 5 alpha-reduction of androgens in the rat prostate. 377 31


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