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)

The testicular feminization syndrome (TFS) in its complete form results in total feminization due to a nuclear inaction of androgens, and the female role should be supported with postpubertal orchiectomy to avoid the risk of malignancy. Incomplete forms of the syndrome (ITFS) include Type I n which some degree of masculinization may be observed, prompting earlier gonadectomy, and Type II or pseudovaginal perineoscrotal hypospadias (PPSH) which is always characterized by pubertal masculinization, necessitating management and support of these patients as males. Other intersex abnormalities which must be differentiated include true hermaphroditism, the Swyer syndrome, males with 17-ketosteroid reductase deficiency, and Reifenstein's syndrome.
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PMID:Testicular feminization syndrome: current clinical considerations. 77 12

Gonadal histology was investigated by means of conventional microscopy in 6 patients with complete androgen insensitivity syndrome, in 11 with incomplete androgen insensitivity syndrome, and in 3 with 5 alpha-reductase syndrome. Twelve subjects were prepubertal and 8 pubertal. In all patients gonadal tissue was removed as a prophylactic measure and no patients gave rise to any clinical suspicion of a tumour. Eight patients with incomplete androgen insensitivity syndrome, 5 of whom (62.5%) were prepubertal, showed intratubular germ cell neoplasia and in 6 of them it was bilateral. Histochemical and immunohistochemical analysis showed considerable agreement between atypical morphological aspects and positive response to Schiff's periodic acid and to staining with the anti-placenta alkaline phosphatase antibody. Our patients were characterized by one of the highest reported incidences of intratubular germ cell neoplasia, particularly at prepubertal age. These findings would seem to indicate that a rethink is needed concerning the general opinion that patients with androgen intensivity syndrome have practically no risk of developing malignancy, and that orchidectomy is not advisable before puberty is completed.
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PMID:Incidence of intratubular germ cell neoplasia in androgen insensitivity syndrome. 217 24

The hormonal activity of androgens is mediated in target cells, particularly in human skin, by two kinds of proteins: the androgen receptor and the enzyme 5 alpha-reductase. In well differentiated androgen target cells, 5 alpha-reductase achieves the transformation of testosterone (T) into dihydrotestosterone (DHT), a more active androgen than T, because of its higher affinity for the receptor. In other words, 5 alpha-reductase acts as an amplifier of the androgen signal but is not absolutely required for androgen action. Regarding the regulation of the androgen receptor, minimal information is available. However, in genital skin, the receptor seems to be predominantly localized in the cytosolic compartment before puberty in males and in the nuclear compartment after puberty. In hirsute patients, recent data on genital skin fibroblasts do not show significant differences between the binding capacity of fibroblasts from normal and hirsute women whereas there is no difference between normal men and women. 5 alpha-Reductase activity seems to be a very important step in the processes involved in androgen action. While 5 alpha-reductase activity present in the skin of external genitalia does not seem to be androgen dependent, this is not the case for the enzyme located in pubic skin. In this area, a sex difference between males and females may be observed both in skin homogenates and in cultured fibroblasts. In addition DHT added to a medium of pubic skin fibroblasts is capable of increasing 5 alpha-reductase activity. This increase is not observed when cyproterone acetate is added to the medium and in patients with testicular feminization syndrome without receptors. Pubic 5 alpha-reductase activity is an androgen receptor mediated phenomenon. In patients with hirsutism, and particularly idiopathic hirsutism, 5 alpha-reductase activity is high without an increase in circulating androgens. This may be observed both in pubic skin homogenates and in cultured fibroblasts. Thus, an excess of skin 5 alpha-reductase activity may be considered as a cause of hirsutism but both the exact level of the abnormality in the regulation of the enzyme and its genetic control remain to be elucidated.
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PMID:Regulation of androgen receptor and 5 alpha-reductase in the skin of normal and hirsute women. 294 Nov 88

Two siblings with the classical phenotype of complete androgen insensitivity syndrome (CAIS) and increased total cellular androgen receptor concentrations in genital skin fibroblasts (GSF) are described. Testosterone biosynthesis was normal, and there was no evidence of 5 alpha-reductase deficiency. Specific binding of [3H]dihydrotestosterone ([3H]DHT) in GSF was 7 SD above the mean value in normal fibroblast strains [maximum binding, 775 +/- 185 X 10(-18) mol/micrograms DNA (mean +/- SD)]. Binding at 40 C was stable, and the androgen-receptor complex dissociated at a normal rate (t1/2, 85 min). The androgen-receptor complex from GSF cytosol sedimented at 5-6S on sucrose density gradients in the presence of sodium molybdate. In a whole cell binding assay, the percentage of [3H]DHT that bound to a crude nuclear pellet was 60%. Preincubation of GSF with 2 nM [3H]DHT for 20 h before the standard 1-h whole cell binding assay produced a further augmentation in elevated total cellular androgen receptor concentrations. A new variant of CAIS is described which is characterized by an increased concentration of androgen receptors that appear to be quantitatively and qualitatively normal. Augmentation of the receptor by androgen suggests that the gene coding for the androgen receptor is intact and does not account for the androgen insensitivity.
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PMID:Complete androgen insensitivity syndrome characterized by increased concentration of a normal androgen receptor in genital skin fibroblasts. 308 20

The activity of 5 alpha-reductase in genital and supra-pubic skin (homogenate or fibroblasts) from subjects with complete or incomplete androgen insensitivity syndrome was low compared with mean activity in samples from normally differentiated male controls. Also, in two subjects with incomplete androgen insensitivity syndrome the ratio of the concentration of testosterone to that of 5 alpha-dihydrotestosterone in plasma was raised after hCG stimulation but normal under basal conditions. In three subjects with complete androgen insensitivity syndrome there was no evidence of raised ratios of testosterone to 5 alpha-dihydrotestosterone in plasma under basal or hCG-stimulated conditions. The activities of other steroid metabolizing enzymes, e.g. 17 beta-hydroxysteroid dehydrogenase, 3 alpha/beta-hydroxysteroid dehydrogenase, were not decreased. The low 5 alpha-reductase activity of androgen insensitive subjects reported here, and by others, may imply that this enzyme in genital skin is in some way androgen dependent, or responsive to other factors associated with androgen insensitivity syndrome.
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PMID:Evidence for secondary 5 alpha-reductase deficiency in genital and supra-pubic skin of subjects with androgen insensitivity syndrome. 316 58

The syndromes of androgen resistance illustrate a special field of endocrinology, that is pathology of target-tissues. These syndromes are responsible for male pseudohermaphroditism and provoke in XY subjects, with a normal testicular androgen secretion, abnormalities in the phenotype with all the possibilities from an "idealistically" female phenotype in the testicular feminization syndrome to an almost normal male phenotype in the mildest forms of the incomplete syndrome. Understanding of these syndromes has strongly benefited of progress in biochemistry and molecular biology concerning the mechanism of action of androgens. On the other hand, understanding androgen mechanism expanded markedly from parallel clinical observation and biochemical investigation permitted by methodological progress: plasma hormones assays, 5 alpha-reductase and androgen receptor qualitative and quantitative determinations. The complete form of the testicular feminization syndrome seems to be due--in most cases--to an absence of the androgen receptor whereas the incomplete forms of the syndrome are related either to insufficient amount or qualitative alteration of the receptor or to a defect of 5 alpha-reductase, the key-enzyme which transforms testosterone to its active metabolite dihydrotestosterone in androgen target-cells. In some cases (approximately equal to 10%) the mechanism of androgen insensitivity could not be identified. The abnormality might be downstream the receptor at various possible steps = binding of the complex androgen-receptor to the chromatin, transcription or post-transcription process. These cases can be useful models for understanding the ultimate steps of the androgen mechanism of action.
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PMID:[Androgen insensitivity syndromes]. 331 78

The prevalence of neoplasia is increased in individuals with certain disorders of sexual differentiation. Etiology and frequency of neoplasia vary with the particular disorder. In uncomplicated cryptorchidism, the testis is at least 10 times more likely to undergo neoplastic transformation than a normal scrotal testis. Neoplasia probably is a function of both testicular location (intraabdominal) and underlying dysgenetic structure. If cryptorchidism is unilateral, and if orchiopexy has not been performed prior to age 6-10 years, orchiectomy should be encouraged. In those forms of gonadal dysgenesis not associated with a Y chromosome (e.g., 45,X; 45,X/46,XX; 46,XX) there is no definite increase in neoplasia, suggesting that elevated gonadotropin levels per se are not carcinogenic. Gonadal tumors are found in at least 30% of individuals with XY gonadal dysgenesis and are particularly frequent (55%) in H-Y antigen-positive patients. These tumors are almost always gonadoblastomas or dysgerminomas. Similar tumors are found in 15%-20% of 45,X/46,XY individuals. In either situation the neoplastic transformation could be a) secondary to the existence of XY gonadal tissue in an inhospitable environment, or b) integrally related to that process--genetic or cytogenetic--producing the dysgenetic gonads. The risk of neoplasia is sufficiently high that most of these patients should be offered early gonadal extirpation. The prevalence of gonadal tumors is not increased in Klinefelter's syndrome, further indicating that gonadotropins are not carcinogenic per se. However, Klinefelter patients are 20 times more likely to develop a carcinoma of the breast than are 46,XY males. Extragonadal germ cell tumors also are more common. In female pseudohermaphrodites there is probably no increased risk of neoplasia, whereas, in true hermaphrodites neoplasia is unusual but does occur. Neoplasia occurs in patients with complete testicular feminization (complete androgen insensitivity) but rarely in those with incomplete testicular feminization/Reifenstein's syndrome, 5 alpha-reductase deficiency, anorchia, agonadia, or testosterone biosynthetic defects. In complete testicular feminization the risk of malignant tumors is small prior to age 25. After age 25, it is about 2%-5%. Orchiectomy is recommended after pubertal feminization.
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PMID:Abnormal sexual differentiation and neoplasia. 354 44

A case of male pseudohermaphroditism with 47,XYY karyotype in blood and cutaneous fibroblasts is described. The plasma testosterone response to HCG stimulation was slightly below the normal range on two occasions suggesting a deficit of gonadal function. A study of the receptors for dihydrotestosterone in fibroblasts of genital and nongenital skin showed a normal concentration of receptors in genital skin; 5-alpha-reductase activity in fibroblasts of the genital skin was low, but the plasma relationship testosterone/dihydrotestosterone under HCG stimulation was normal. The diagnostic possibility of a complete testicular feminization syndrome with normal receptors for dihydrotestosterone is commented on.
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PMID:A case of male pseudohermaphroditism with normal androgen receptor binding and 47,XYY karyotype. 387 63

In 22 children with male pseudohermaphroditism, plasma concentrations of testosterone and dehydroandrosterone sulfate were measured before and after HCG stimulation. In ten of them, nitrogen retention was measured both before and during treatment with testosterone-propionate. The results of this investigation allow the patients to be classified in the following groups 1) nine in which both the testicular function and the end-organ sensitivity to androgens were normal; 2) nine patients had an abnormal testicular function; 3) four patients had the testicular feminization syndrome. In addition, in one adolescent patient with familial male pseudohermaphroditism and gynecomastia, the pattern of plasma androgens under basal conditions, after HCG and following gonadectomy, suggest that the patient had an incomplete 17-ketosteroid reductase defect.
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PMID:Children with male pseudohermaphroditism: endocrine and metabolic studies. 428 22

In vivo, the 5 alpha-reduction of testosterone (T) to dihydrotestosterone (DHT) is androgen dependent in pubic skin but not in the skin of the external genitalia. The aim of the present study was to determine whether pubic skin fibroblasts (PSF) had retained this androgen dependency. PSF were prepared from explants of skin from normal subjects (four men, three women) and three patients with complete form of the testicular feminization syndrome. Culture medium containing 5% fetal calf serum and DHT was added 24 h after subculture (day 1) and renewed every other day. 5 alpha-Reductase was assayed on day 4 or day 8 by incubation of intact cell monolayers with [3H]T (2 nM), extraction of the medium, and chromatography of the metabolites; DNA was assayed in the cell pellets; 5 alpha-reductase was expressed as fmol/micrograms DNA . h. Controls were untreated plates from the same subcultures. DHT had no effect on cell DNA, whereas it resulted in a dose-dependent increase in 5 alpha-reductase activity. In seven PSF strains tested, DHT (10(-7) M) increased 5 alpha-reductase activity 2- to 4-fold over the control levels. This effect was abolished by the simultaneous addition of cyproterone acetate (2 X 10(-6) M) and was not observed in PSF from testicular feminization syndrome patients, suggesting that it was indeed mediated via the androgen receptor. T but not estradiol or cortisol also increased 5 alpha-reductase activity in PSF. The effect of androgens was suppressed by protein synthesis inhibitors. These data provide strong evidence that PSF respond to androgens via a receptor mediated mechanism, and that 5 alpha-reductase can be used as a marker of androgen action in pubic skin in vitro as well as in vivo.
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PMID:Dihydrotestosterone stimulates 5 alpha-reductase activity in pubic skin fibroblasts. 621 82


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