UNIPROT:Q7LGC8 - FACTA Search

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Query: UNIPROT:Q7LGC8 (HSD)
3,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies within the Arab population in Israel revealed 25 pseudohermaphrodites due to 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) deficiency. Twenty-three individuals, presently living in the Gaza strip, belong to a very large inbred kinship which extends over 8 generations. All affected subjects (46, XY) were born with mild to moderate degrees of ambiguity of an apparently normal-looking female genitalia and therefore were reared as girls. In childhood, genital abnormalities consisted of a clitoral-like phallus surrounded by a chordee, non-fused labial-scrotal folds and a urogenital sinus. The testes were in the inguinal canals, or rarely, in the labial-scrotal folds. Wolffian structures were normally differentiated while Mullerian structures were absent. At puberty, subjects developed a male body habitus with abundant body hair and beard. Gynecomastia was absent. The phallus and testes enlarged to adult proportions while the prostate remained small. Together with the physical change from girls to boys they developed a male identity having erections and ejaculations, which in 7 cases led to the spontaneous adoption of a male gender role. In adults the hormonal abnormalities consisted of greatly elevated delta 4-androstenedione (delta 4) (350-1267 ng/dl) associated with subnormal testosterone (T) levels (0.9-3.1 ng/ml). Dihydrotestosterone (DHT) levels, with the exception of 1 patient, were relatively low in all cases (27-35 ng/dl). Children had low levels of delta 4, T and DHT, which were normal for age. Although from puberty on there was a significant rise of the 3 androgens, delta 4 always remained extremely elevated and T and DHT relatively low when compared to normal controls. Dexamethasone failed to suppress the androgen pattern while HCG augmented the defect, making the diagnosis possible in 2 prepubertal children. Dehydroepiandrosterone (DHEA) and 17-hydroxyprogesterone (17-OHP) levels were normal or moderately elevated. Estradiol (E2) levels were normal in children and all but 2 adults, who had high levels. LH and FSH levels were very high after puberty, but normal before. However, there was an overresponse to LHRH in all age groups. The contrast between the lack of intrauterine virilization of the external genitalia in fetuses with 17 beta-HSD deficiency versus the marked masculinization that occurs after puberty still remains a puzzling phenomenon. It is conceivable that the postpubertal development of a male phenotype with change of gender identity and role occurs due to the joint effect of delta 4, T and DHT, even though secreted in inadequate proportions. Thus masculinization in these individuals is a slow process requiring a longer period of time than that of normal puberty to be completed.
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PMID:Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency: studies on the natural history of the defect and effect of androgens on gender role. 631 Feb 48

The findings of normal testosterone, high normal delta 4 androstenedione, normal 17 OH progesterone and raised DHAs in a young girl of 16 who had regular periods and hirsutism made us think of block in 3 HSD. The 17 OH pregnenolone was raised. Dexamethasone (0.5 mg/24 h) treatment was effective for the hirsutism.
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PMID:[Hirsutism with partial blockage of 3 beta OL hydroxysteroid dehydrogenase (author's transl)]. 694 79

11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the conversion of corticosterone to inert 11-dehydrocorticosterone, thus regulating glucocorticoid access to intracellular receptors. This type 1 isoform (11 beta HSD-1) is a bidirectional NADPH(H)-dependent enzyme in vitro and is highly expressed in liver, where it is regulated by glucocorticoids, thyroid hormones, estrogen, and GH in vivo. In humans in vivo, enzyme inhibition alters glucose homeostasis, an effect thought to be mediated in the liver. However, detailed investigation of the biology of 11 beta HSD-1 in liver, its function, regulation, and indeed even reaction direction, has been hampered by the lack of clonal hepatic cell lines that express 11 beta HSR-1. Studies of nonhepatic cell lines have suggested that 11 beta HSD-1 is directly regulated by hormones, and transfection of nonhepatic cell lines has sown that reaction direction varies between cell types, possibly reflecting intracellular cosubstrate (NADP+/NADPH) ratios or PH. To investigate reaction direction and gene regulation of 11 beta HSD-1 in hepatocytes, we defined conditions for primary culture of adult rat hepatocytes that maintain high 11 beta HSR-1 messenger RNA expression. In intact primary hepatocytes over a wide range of steroid concentrations (2.5-250 nM), 11 beta-reduction was the predominant reaction direction [33.5 +/- 0.5% conversion of 11-dehydrocorticosterone (25 nM) to corticosterone after 30 min], with undetectable 11 beta-dehydrogenation. However, homogenates of hepatocyte cultures showed plentiful 11 beta-dehydrogenase activity. Treatment of hepatocyte cultures with the metabolic inhibitors sodium azide (5 nM) and KCN (1 nM) altered cellular NADP+/NADPH ratios from 0.244 +/- 0.042 in controls to 0.020 +/- 0.001 and 0.152 +/- 0.009, respectively, but had no effect on 11 beta-reductase or 11 beta- dehydrogenase activity. High concentrations of KCN (10 mM) modestly increased 11 beta-reductase activity (32.4 +/- 1.7% to 48.8 +/- 0.5%, whereas 11 beta-dehydrogenation remained at the limit of detection. Manipulation of culture medium pH (6.2-8.0) had no effect on enzyme activity. Dexamethasone (10-7 M) induced hepatocyte 11 beta-reductase activity from 23.4 +/- 0.7% to only weakly affects reaction direction. Glucocorticoid and insulin regulation of hepatic 11 beta HSD-1 is directly mediated, but other hormonal controls are either lost in culture or mediated indirectly. This primary hepatocyte culture system will allow investigation of the control of 11 beta-reductase activity and its implications for glucocorticoid-regulated hepatic functions.
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PMID:11 beta-hydroxysteroid dehydrogenase is an exclusive 11 beta- reductase in primary cultures of rat hepatocytes: effect of physicochemical and hormonal manipulations. 758 3

Selectivity to aldosterone (Aldo) in mineralocorticoid target tissues has been suggested to be due to the activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). This enzyme inactivates the endogenous glucocorticoid cortisol, thus permitting the unhindered access of Aldo to the mineralocorticoid receptor. The 11 beta-HSD activity was measured by the conversion of cortisol to cortisone and vice versa. Concomitant treatment of the cells with either cortisone or cortisol in the presence of the glycyrrhetinic acid derivative carbenoxolone (CBX) blocked both activities of 11 beta-HSD. Dexamethasone and Aldo activated the transcription of transiently transfected mouse mammary tumor virus-bacterial chloramphenicol acetyltransferase chimeric gene in LU-19 cells. The transcription activation by cortisol was synergized by concomitant treatment of the transfectants with CBX. Transactivation with Aldo was inhibited by spironolactone. The enzyme 11 beta-HSD in LU-19 cells is similar to the cloned liver isoform and catalyzes both reduction and dehydrogenation.
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PMID:11 beta-hydroxysteroid dehydrogenase activity in human lung cells and transcription regulation by glucocorticoids. 794 49

The level of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) mRNA in the fetal sheep liver increases dramatically between day 130 and term (term = day 145), but the causal factors remain unknown. The present study was designed to determine the effects of exogenous glucocorticoid on the fetal hepatic 11 beta-HSD gene expression. Dexamethasone (dex; 2 micrograms/min over 15 min every 2 h) or saline was infused into chronically-catheterized fetal sheep at day 130 of gestation for 4 days. At the end of infusion, the lower right lobe of the liver was collected, total cellular RNA extracted and subjected to Northern blot analysis. It was found that the level of the hepatic 11 beta-HSD mRNA in dex-treated fetuses was about four times higher than that in the saline-treated controls. To examine whether changes occur in the response of hepatic 11 beta-HSD gene expression to glucocorticoids in adulthood, we also treated non-pregnant ewes with dex (10 mg/day) for 4 days. By contrast, this treatment regime in adult sheep produced a small but significant decrease in hepatic 11 beta-HSD mRNA levels. We also determined whether age-specific changes in the hepatic level of 11 beta-HSD mRNA following dex treatment were reflected in the level of 11 beta-HSD enzyme activity. Hepatic 11 beta-HSD activity was determined by a standard in vitro conversion assay using cortisol and cortisone as physiological substrates. In both fetal and adult livers, 11-oxoreductase activity (cortisone-->cortisol) was predominant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Opposite effects of glucocorticoid on hepatic 11 beta-hydroxysteroid dehydrogenase mRNA and activity in fetal and adult sheep. 796 10

The induction of Na,K-ATPase plays a vital role in mediating epithelial sodium transport. Although its activity is regulated by corticosteroids, it is uncertain whether this is predominantly by mineralo- or glucocorticoid mechanisms. 11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the interconversion of active corticosterone (B) to inactive 11-dehydrocorticosterone and protects the nonselective mineralocorticoid receptor (MR) from glucocorticoid excess. We have studied the regulation of the alpha 1- and beta 1-subunits of Na,K-ATPase by mineralo- and glucocorticoids in vitro and in vivo, and how this is modulated by 11 beta HSD activity. Cultured rat kidney epithelial cells (NRK 52-E) expressed 11 beta HSD activity, which was inhibited by the licorice derivative glycyrrhetinic acid (GE). Dexamethasone, aldosterone, and high concentrations of B (1-10 microM) increased Na,K-ATPase alpha 1 and beta 1 messenger RNA (mRNA) levels, an effect that was inhibited by coincubation with the MR antagonist RU 26752, but not by the glucocorticoid receptor antagonist RU 38486. GE, which itself reduced Na,K-ATPase alpha 1/beta 1 mRNA levels, potentiated the action of B, so that low concentrations of B (10 nM) increased Na,K-ATPase alpha 1/beta 1 mRNA levels. In contrast, in vivo, RU 26752 and RU 38486 given ip for 4 days (n = 6/group) reduced renal Na,K-ATPase alpha 1 and beta 1 levels. Glycyrrhizic acid also inhibited both renal 11 beta HSD mRNA and activity and levels of Na,K-ATPase alpha 1/beta 1 mRNA. In vivo renal Na,K-ATPase subunit mRNA levels are regulated by both mineralo- and glucocorticoid mechanisms. In vitro, however, although NRK 52-E cells expressed the glucocorticoid receptor, corticosteroid regulation of Na,K-ATPase, even by dexamethasone, occurred exclusively via the MR, suggesting that accessory transcription factors required for glucocorticoid hormone action are absent in this cell line. Finally, although the licorice derivatives GE and glycyrrhizic acid reduced Na,K-ATPase alpha 1/beta 1 mRNA levels, they also potentiated the stimulatory effect of B by inhibiting its metabolism via 11 beta HSD, establishing 11 beta HSD as an important prereceptor modulator of mineralocorticoid hormone action.
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PMID:Regulation of sodium-potassium adenosine triphosphate subunit gene expression by corticosteroids and 11 beta-hydroxysteroid dehydrogenase activity. 807 Mar 85

The enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD) converts corticosterone to the inactive 11-dehydrocorticosterone in the rat. The bioactivity of 11-HSD, expressed as the percentage conversion of 3H-corticosterone to 3H-11-dehydrocorticosterone, was 13.7 +/- 0.4% in rat vascular smooth muscle cells (rVSMC). Cells treated with 100 nM dexamethasone (Dex) showed a 1.4-fold (p < 0.05) increase in 11-HSD activity. Insulin (100 microM) decreased 11-HSD activity by 0.8-fold (p < 0.05). Expression of 11-HSD mRNA was also confirmed in rVSMC by Northern blot analysis. Dexamethasone increased and insulin decreased the levels of 11-HSD mRNA in parallel with the increase in bioactivity. Vascular smooth muscle cells express 11-HSD activity; the access of corticosterone to vascular smooth muscle receptors may be modulated by the enzyme.
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PMID:Expression of 11 beta-hydroxysteroid dehydrogenase mRNA in rat vascular smooth muscle cells. 828 89

The postpubertal clinical presentation of 3 beta-hydroxysteroid dehydrogenase deficiency (3B-HSD deficiency) is less well-defined for adult males than for adult females, who often present with hirsutism. We describe a male with normal puberty who presented with new-onset gynecomastia at age 24. Common causes of gynecomastia were excluded. Dehydroepiandrosterone-sulfate (DHEA-S), estradiol, estrone, and 24-hour urinary 17-ketosteroid levels were elevated. A feminizing tumor was considered; biochemical tumor markers, chest x-ray, ultrasound of testes, and abdominal computed tomography (CT) scan were negative. Dexamethasone-suppression testing showed normal suppression of 24-hour urinary adrenal steroids. Cosyntropin-stimulation testing showed normal cortisol, 11-deoxycortisol, 17-OH progesterone (17-OHP), and aldosterone levels, but significant elevations of pregnenolone (preg), 17-OH preg, progesterone, DHEA, and androstenedione (A) levels. The sperm count was high and gonadotropin-releasing hormone (GnRH)-stimulation testing showed a normal increase in testosterone (T) level, suggesting that the defect did not involve the testes. It is concluded that this patient's gynecomastia is due to 3B-HSD deficiency with an associated alteration in sex hormone ratios. To our knowledge, this is the first well-described adult male with normal gonadal function presenting with postpubertal gynecomastia due to 3B-HSD deficiency. This defect may be a frequently unrecognized cause of gynecomastia.
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PMID:Partial 3 beta-hydroxysteroid dehydrogenase deficiency presenting as new-onset gynecomastia in a eugonadal adult male. 844 50

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) catalyzes the conversion of the glucocorticoid corticosterone (cortisol in humans) to inert 11-dehydrocorticosterone (cortisone). 11 beta-HSD activity is present in the hippocampus, where it is induced by glucocorticoids and stress in vivo, prompting suggestions that the enzyme may attenuate the deleterious effects of chronic glucocorticoid excess on neuronal function and survival. Two isoforms exist: 11 beta-HSD1, a bidirectional NADPH-dependent enzyme, and 11 beta-HSD2, an NAD(+)-dependent exclusive 11 beta-dehydrogenase (corticosterone-inactivating enzyme). In this study, 11 beta-HSD1 activity and mRNA synthesis were demonstrated in primary fetal hippocampal cell cultures. Unexpectedly, the reaction direction in intact hippocampal cells was 11 beta-reduction (reactivation of inert 11-dehydrocorticosterone), although homogenization revealed that the enzyme was capable of 11 beta-dehydrogenation when removed from its normal cellular context. Dexamethasone (10(-7) M) increased 11 beta-HSD activity in homogenates of hippocampal cultures (102% increase). In intact hippocampal cells, dexamethasone induced 11 beta reductase, not dehydrogenase. To determine the functional relevance of hippocampal 11 beta-reductase, glucocorticoid potentiation of kainic acid neurotoxicity was examined. Pretreatment of hippocampal cells with corticosterone reduced survival on kainate exposure. Hippocampal cell 11 beta-HSD activity was potently inhibited by carbenoxolone. Carbenoxolone had no effect on cell survival after kainate alone and did not alter the effect of corticosterone. 11-Dehydrocorticosterone also potentiated kainate neurotoxicity; this effect was lost, however, if 11 beta-HSD was inhibited with carbenoxolone. Thus, hippocampal 11 beta-HSD seems to be a functional 11 beta-reductase in intact cells. Measures to attenuate hippocampal 11 beta-reductase may reduce neuronal vulnerability to glucocorticoid toxicity.
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PMID:11 beta-Hydroxysteroid dehydrogenase in cultured hippocampal cells reactivates inert 11-dehydrocorticosterone, potentiating neurotoxicity. 861 10

The syndrome of apparent mineralocorticoid excess (AME) is a heritable form of hypertension due to an inborn error of cortisol metabolism and is characterized by hypokalemia and low renin levels despite subnormal or normal levels of aldosterone and other known mineralocorticoids. The syndrome is attributable to congenital deficiency of the enzyme 11 beta-hydroxydehydrogenase (11 beta-HSD), which converts cortisol (F) to biologically inactive cortisone. This results in a prolonged half-life of F, which acts at the kidney level as a potent mineralocorticoid (MC). In fact, both F and aldosterone have similar affinities in vitro for type I MC receptor (MR), and 11 beta-HSD activity protects the MR in vivo from the higher circulating levels of F. The biochemical marker of this disorder is an increased ratio of tetrahydrocortisol (THF) + allo-THF/tetrahydrocortisone (THE) in the urine, which has been found in more than 20 patients described to date, together with evidence of a more general defect in steroid ring A reduction. Only a few cases (the so-called type II form) described in Italy differ from the classic form having a normal THF/THE ratio, but in both forms the ratio of free urinary F/E has recently been found to be similarly high. Dexamethasone is the treatment of choice but is often inadequate in long term control of high blood pressure. Acquired forms of AME are those consequent on abuse of licorice or carbenoxolone, which both inhibit 11 beta-HSD; the latter also inhibits the reverse 11-oxoreductase reaction leading to somewhat different abnormalities of urinary cortisol/cortisone. So far, two isoenzymes of 11 beta-HSD have been purified and cloned; 11 beta-HSD type 1 is NADP-dependent, abundant in liver, lung, and testis, and catalyzes both 11 beta-dehydrogenation and 11 beta-oxoreduction; no mutation in its gene was detected in patients with AME. A second NAD-dependent isoenzyme is present in kidney and placenta and catalyzes dehydrogenation only. Very recently (1995) two groups have independently demonstrated the presence of mutations in its gene, located in chromosome 16q22. New and co-workers found a point mutation in exon 6 of two affected siblings of an Iranian family, while White and co-workers in parallel studies showed point mutations or small deletions in both alleles in nine unrelated patients; importantly, expression studies showed minimal or absent activity for almost all the mutant sequences. No definite mutations have been so far identified in patients with AME type II. AME is thus the third single gene cause of human hypertension to be described, after glucocorticoid remediable aldosteronism in 1992 and Liddle's syndrome in 1994.
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PMID:Apparent mineralocorticoid excess: type I and type II. 873 99

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