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)

Megestrol acetate (Megace), an antiandrogen, was administered in a dosage of 80 mg daily to 6 patients with benign prostatic hypertrophy (BPH) for 4 to 25 days prior to transurethral resection of the prostate (TURP). Surgical tissue from drug-treated patients was compared to untreated controls in regard to: 1) the enzymatic reduction of testosterone (T) and dihydrotestosterone (DHT); 2) DHT binding to a cytosol receptor protein; 3) tissue levels of endogenous dihydrotestosterone and androstanediols (diols). When minced prostate was incubated with 3H-T and 14C-androstenedione for 1 h at 37 C, prostate 5alpha-reductase activity, measured as reduced products formed from substrate, decreased to 31% and 39%, respectively, of the control values. Prostate 3-oxido-reductase enzyme activity, measured as diols formed from 3H-DHT, was decreased to neglible values in Megace-treated patients compared to an 8.7% conversion to diols in controls. No 3H-DHT binding to a cytosol receptor protein could be demonstrated in 4 out of 5 prostates from Megace-treated patients, whereas the presence of such a receptor was noted in 14 out of 17 untreated controls. Endogenous DHT levels in Megace-treated patients averaged 1.1 ng/g (SE = 0.26), significantly less than the average of 3.9 ng/g (SE = 0.49) found in controls (P less than 0.001). No significant difference was noted in endogenous diols. In addition to these effects on tissue, Megace significantly decreased plasma levels of T, LH, and FSH at the end of the 4- to 25-day period; plasma prolactin levels did not change. Continued studies of Megace for the possible treatment of benign prostatic hypertrophy may be warranted since the drug appears to block several important biochemical steps which mediate the effects of androgen on the human prostate.
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PMID:Effect of megestrol acetate (Megace) on steroid metabolism and steroid-protein binding in the human prostate. 6 59

We studied a 17 year old patient with primary amenorrhea, hirsutixm, clitoral enlargment, poor breast development and 46, XY karyotype. The results shown in table clearly indicate a 17-ketosteroid reductase deficiency. In the view of previously described patients we can conclude that: 1) intensity of virilisation depends on both plasma testosterone and androstenedione levels; 2) importance of gynecomastia depends on plasma E2 but not E1 levels; 3) FSH levels are not correlated with circulating androgens or estrogens but presumably depends on importance of seminiferous tubules' lesions.
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PMID:[Study of a new case of male pseudohermaphroditism due to 17-ketosteroid reductase deficiency (author's transl)]. 12 Dec 23

The following physiopathological mechanisms for the abnormalities of testosterone metabolism observed in cirrhotic patients may be postulated: 1. The decreased testosterone secretion has a primary testicular origin; it seems probable that, as a result of direct toxicity the 17-beta-reductase is inhibited, resulting in decrease of testosterone and an increase of androstenedione. 2. The hypothalamic-pituitary function is nearly normal in cirrhotics. Basal level of LH and FSH are often slightly elevated, indicating a normal reactivity of the pituitary. 3. The conversion of androgens to oestrogens (androstenedione to oestrone) which occurs essentially extrahepatically, is increaed in cirrhosis.
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PMID:Testosterone metabolism in normal males and male cirrhotics. 15 39

The present study evaluates the relationship between periodontal status, concentration of circulating hormones and metabolism of androgens by human male and female gingiva in vitro. In both male and female patients with healthy gingiva the plasma concentration of gonadotropins (LH and FSH) and steroid hormones (testosterone, androstenedione, estradiol-17 beta, progesterone and cortisol) were in a normal range. However, an alteration in the plasma concentration of progesterone was found in both male and female patients with periodontal pathosis. Both androgens (testosterone and androstenedione) were readily metabolized by human gingiva tissue in vitro. The major pathway of the metabolism of testosterone was via the formation of 17 beta-hydroxy-5 alpha-A-ring reduced androgens (5 alpha-dihydrotestosterone and 3 alpha-, 3 beta-androstanediol). In contrast, androstenedione was metabolized mainly to 17-keto-5 alpha-A-ring reduced (5 alpha-androstanedione, androsterone and epiandrosterone) and 17 beta-oxidoreduced (testosterone) compounds. In addition both substrates were metabolized to 5 beta-A-ring reduced androgens (5 beta-dihydrotestosterone, 5 beta-androstanediol and 5 beta-androstanedione). A significant feature of the metabolism of testosterone and androstenedione by inflamed gingiva was an increase of 5 alpha-A-ring reductase activity (mainly the formation of 5 alpha-dihydrotestosterone and 5 alpha-androstanedione) and 17 beta-oxidoreductase activity (mainly the formation of testosterone from androstenedione). The increase in 5 alpha-reductase activity also showed a significant correlation with the plasma progesterone concentration.
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PMID:Concentration of circulating hormones and metabolism of androgens by human gingiva. 28 81

Cultures of Sertoli cells isolated from testes of 18-and 36-day-old Long Evans rats were used to investigate their capacity to metabolize testosterone and the effect of FSH on such metabolism. Three different approaches were used: 1) investigation of the metabolism of radiolabeled testosterone under saturating substrate conditions; 2) study of the metabolism of radiolabeled testosterone utilizing trace amounts of high specific activity substrates; 3) the utilization of radioimmunoassay for measurement of estradiol-17 beta. The following steroids were isolated and identified by recrystallization to constant specific acitvity from the control and FSH-treated cultures; testosterone (unconverted substrate), androstenedione, dihydrotestosterone, 3 alpha-hydroxy-5 alpha-androstan-17-one and 5 alpha-androstane-3 alpha, 17 beta-diol. Radioimmunoassay data suggests that the Sertoli cells produce an estradiol-17 beta-like compound from unlabeled testosterone and that this production is stimulated by FSH. However, the radioactive metabolite from all our studies that behaved chromatographically like estradiol--17 beta failed to crystallize to constant specific activity, while in each experiment, authentic radiolabeled estradiol-17 beta added as recovery tracer did. The data demonstrate that : 1) cultures of Sertoli cells from immature rats have 5 alpha-reductase, 3 alpha- and 17 beta-hydroxysteroid oxidoreductase activities; 2) these enzymes may be affected by FSH; 3) based on radiolabeled metabolic techniques, Sertoli cells were unable to biotransform testosterone to estradiol-17 beta even in the presence of FSH.
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PMID:In vitro metabolism of testosterone by cultured Sertoli cells and the effect of FSH. 31 14

The reduction of 4-[1,2-3H]androstene-3,17-dione (androstenedione) in vitro by scrotal skin was measured in samples from nine men (16--34 years old) with hypospadias and from ten male control subjects. The reduction of androstenedione was also studied in axillary and upper arm skin of seven control subjects. Androstenedione was reduced to material with chromatographic characteristics of 5 alpha-androstane-3,17-dione and to 3 alpha- and 3 beta-hydroxy-5 alpha-androstan-17-one. No difference in 5 alpha-reductase activity (defined as the sum of these three metabolites formed) was found in scrotal skin from hypospadic and control men. The mean concentration of 5 alpha-dihydrotestosterone in serum from men with hypospadias was lower than that in serum from control subjects (P less than 0.01). The mean ratio of the serum concentrations of testosterone and 5 alpha-dihydrotestosterone was higher in hypospadic men than in control subjects (P less than 0.05). No differences between the two groups were found in the mean serum concentrations of LH, FSH, prolactin, dehydroepiandrosterone, androstenedione, testosterone or testosterone-binding globulin.
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PMID:Reduction of androstenedione by skin in vitro and serum levels of gonadotrophins and androgens in men with hypospadias. 51 49

Flutamide, a nonsteroidal antiandrogen, was given to 11 men with prostate cancer, in doses of 750 to 1500 mg daily for 0.5--7 months. Four patients had a clinical remission and seven showed no response. All the patients showed a profound change in the peripheral metabolism of testosterone: markedly increased conversion to androsterone (A) and correspondingly decreased conversion to etiocholanolone (E); the A/E ratio rose to levels never before observed consistently in any group of healthy or diseased humans. This change was probably due to alteration by flutamide of the relative activities of steroid 5alpha and 5beta reductase in favor of the former. 24-Hour mean plasma testosterone was increased in five of the six patients studied for this parameter, for the group as a whole, testosterone rose from 279 ng/dl to 484 ng/dl (P less than .05). 24-Hour mean values for plasma dihydrotestosterone, dehydroisoandrosterone, LH and FSH showed no significant change, for the group as a whole, in the same six patients. Since flutamide did not change the metabolic clearance rate or volume of distribution of testosterone tracers, the increased plasma levels of the hormone were probably due to increased production.
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PMID:The effect of flutamide on testosterone metabolism and the plasma levels of androgens and gonadotropins. 59 17

Four male pseudohermaphrodites from two families have been described. Although reared as females, at puberty, the timing, pattern, and degree of masculinization was similar to that of a normal male. No feminization occurred. They had normal testicular testosterone synthesis as judged by plasma testosterone, LH and FSH concentrations, as well as incubations of testicular minces with labeled precursors. Studies on cultured skin fibroblasts indicated adequate peripheral 5 alpha-reductase and normal receptor affinity and capacity for dihydrotestosterone. The histology of the testis was suggestive of a primary testicular defect. A mosaic pattern was seen: some areas contained tubules with active spermiogenesis; other areas, only Sertoli cells. These male pseudohermaphrodites appear to have a defect in fetal testicular maturation in which inadequate fetal testosterone synthesis and defective differentiation of germinal elements occurred.
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PMID:Familial male pseudohermaphroditism with normal Leydig cell function at puberty. 75 43

A new inherited form of male pseudohermaphroditism has been investigated in a pedigree of 24 families with 38 affected males. At birth, the affected males (46 XY) have a clitoral-like phallus, bifid scrotum and urogenital sinus. The testes are in the inguinal canals or labial-scrotal folds. The Wolffian structures are normally differentiated; there are no Mullerian structures. At puberty a muscular male habitus develops with growth of the phallus and scrotum, voice change and no gynecomastia. The subjects have erections, ejaculations and a libido directed towards females. They have decreased body hair, a scant to absent beard, no temporal hair line recession and a small prostate. Testicular biopsy reveals a normal testis. The mean plasma T levels in affected adults are significantly higher, and the mean plasma DHT levels are significantly lower when compared to those in normal subjects. The plasma T:DHT ratios range from 35 to 84 compared to 8 to 16 in normal subjects. After the administration of hCG, the T:DHT ratios in affected male children range from 74 to 162 compared to 3 to 26 in the control subjects. In affected adults, mean plasma LH and FSH levels are significantly higher than in normal subjects. In the affected subjects, the metabolic clearance rates of T and DHT are normal, but the conversion ratio of T to DHT is less than 1 per cent. The endogenous mean urinary E:A and E-OH:A-OH ratios, and the urinary E:A and E-OH:A-OH ratios after the infusion of radioactive T are significantly higher than in normal males. Inheritance is autosomal recessive with some sibling sisters showing the same biochemical defect, and obligate carrier parents showing an intermediate defect. These data support our thesis that the defect in these male pseudohermaphrodites is secondary to decreased steroid delta 4-5 alpha-reductase activity. The affected subjects provide a clinical model for delineating the roles of T and DHT in sexual differentiation and development. This entity also demonstrates an inherited disorder of steroid metabolism in which the basic enzyme deficiency resides in the target tissues.
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PMID:Male pseudohermaphroditism due to steroid 5-alpha-reductase deficiency. 83 97

Testosterone exerts negative feedback control on gonadotropin secretion either directly, after aromatization to estradiol, or after 5 alpha-reduction to dihydrotestosterone (DHT). Conflicting data exist as to the role of DHT in the modulation of this negative feedback. To determine whether suppression of endogenous DHT alters gonadotropin secretion, we gave the selective 5 alpha-reductase inhibitor finasteride (5 mg daily), or placebo, to 20 healthy men for 28 days. Basal and GnRH-stimulated LH, bioactive LH, FSH, testosterone, and DHT levels were measured before and after 14 and 28 days of treatment. Basal DHT fell from 1.1 +/- 0.2 to 0.15 +/- 0.04 nmol/L after 28 days of finasteride treatment. A significant rise in baseline testosterone from 17.6 +/- 2.0 to 18.3 +/- 2.3 nmol/L was seen at 14 days (P = 0.046), but not at 28 days. No significant changes were seen in either basal or GnRH-stimulated gonadotropin levels on any day. We conclude that suppression of serum DHT levels with 5 mg finasteride daily in healthy young men has no discernible effect on serum gonadotropin levels.
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PMID:Effect of finasteride, a 5 alpha-reductase inhibitor, on serum gonadotropins in normal men. 132 27


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