Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.1.1.3 (HSD)
3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was assayed in various tissues microdissected from the freeze-dried human skin of fourteen subjects. The apocrine sweat gland, sebaceous gland and hair follicle possessed a high activity of 17 beta-HSD. The enzyme activity was negligible in the epidermis, except that the scalp epidermis showed much the same activity as the hair follicle. The demis showed variable activity because of contamination with other components.
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PMID:Activity of 17 beta-hydroxysteroid dehydrogenase in various tissues of human skin. 694 20

We have shown previously that the capacity of the jejunal mucosa to oxidise testosterone to the weaker androgen, androstenedione, by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), is considerable. The present study extends these earlier observations by measuring 17 beta-HSD activity in different regions of the gastrointestinal tract, by investigating the potential for testosterone metabolism by slices and everted sacs of rat jejunum, and estimating the contribution of intestinal testosterone metabolites to circulating levels of plasma androgens, by portal vein sampling in the rat, in vivo. 17 beta-HSD activity in homogenates of gastric and duodenal mucosa was significantly higher than that in jejunum, and was also present in ileum and colon. In addition to androstenedione, slices and everted sacs of rat jejunum produced various metabolites, one of which was probably dihydrotestosterone. It was not, however, a major metabolite in vivo. It is suggested that 5 alpha-reduction may be favoured in vitro by a lower oxidation-reduction potential resulting from tissue anoxia. The major portal vein metabolite was androstenedione, the same major metabolite produced by mucosal homogenates. We conclude that oxidation of testosterone is the major metabolic pathway in intestinal mucosa and the capacity of the gastrointestinal tract to reduce the potency of testosterone is considerable. Our findings suggest that the gut, rather than the liver, is responsible for the failure of oral testosterone to provide effective androgen replacement therapy. The qualitative difference in testosterone metabolism between in vitro and in vivo preparations emphasises the need for caution in the interpretation of similar in vitro experiments.
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PMID:Testosterone metabolism by the rat gastrointestinal tract, in vitro and in vivo. 695 Sep 19

The metabolism of steroid hormones in normal and neoplastic tissue has been studied in the human parotid gland. In vitro incubation of homogenate preparations with either testosterone, oestradiol or DHT resulted in the formation of the corresponding 17-keto metabolite as the major product. Little or no metabolism could be seen when androstenedione, oestrone or 5 alpha-androstan-3,17-dione were used as substrates, demonstrating that the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSDH) in this tissue favours an oxidative reaction pathway, 17 beta-HSDH activity in normal and tumour tissue was compared using both testosterone and oestradiol as substrates. The activity varied between individuals but was, in all cases, significantly elevated in tumour tissue when this was compared with normal. In conclusion, (1) the human parotid gland contains steroid metabolizing enzymes which favour an oxidative reaction pathway, and (2) the 17 beta-HSDH activity is significantly elevated in neoplastic tissue.
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PMID:Steroid metabolism by normal and neoplastic parotid tissue. 695 86

Human parotid and submandibular glands showed no 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity. The 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) appeared intensely reactive in the duct epithelia of the male and female glands and weakly reactive in the acinar cells of the female ones. The failure to demonstrate 3 alpha-HSD activity indicates that in-vivo androgen activation, if present at all, is not so marked as in target organs. The different distribution of the 3 beta-HSD and 17 beta-HSD in the two sexes can be related not only to the oxidation of androgens but also to the metabolism of the female hormones. Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) do not seem to be specifically influenced by the sex hormones as their pattern of distribution showed no sex differences.
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PMID:Histochemistry of the 3 beta-hydroxysteroid, 17 beta-hydroxysteroid and 3 alpha-hydroxysteroid dehydrogenases in human salivary glands. 695 69

The important enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is known to regulate intracellular levels of biologically active steroids, namely, androgens and estrogens. In an effort to develop potent inhibitors of 17 beta-HSD for reducing the levels of active steroids, we found that steroidal spiro-gamma-lactones inhibit 17 beta-HSD activity. In this report, we describe the synthesis of 11 spiro-gamma-lactone analogs containing a steroidal C-18 or C-19 nucleus and compare their relative inhibitory effects on 17 beta-HSD activity in the human placenta microsomes that catalyze the interconversion of androgens and estrogens. To void the interaction of the cytosolic 17 beta-HSD activity that is specific for the interconversion of estrone and estradiol, we used 4-androstenedione as substrate. Analysis of the inhibitory effect exerted by these analogs on microsomal 17 beta-HSD activity indicates that spiro-gamma-lactones containing the C-18 nucleus are more potent inhibitors than C-19 nucleus analogs. The best inhibition was obtained with the phenolic spiro-gamma-lactone 7 (3-hydroxy-19-nor-17 alpha-pregna-1,3,5(10)-triene 21,17-carbolactone), which has an IC50 value of 0.27 microM, and was much lower than the competitive effect of the unlabeled substrate 4-androstenedione, which has an IC50 value of 1.40 microM. Preincubation with lactone 7 did not inactivate 17 beta-HSD activity. The results thus suggest that lactone 7 is a reversible in inhibitor. Lactone 7 is selective for microsomal 17 beta-HSD activity, as no inhibition was observed for cytosolic 17 beta-HSD activity.
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PMID:Steroidal spiro-gamma-lactones that inhibit 17 beta-hydroxysteroid dehydrogenase activity in human placental microsomes. 747 80

The aim of this study was to examine the expression and regulation of type 1 17 beta-hydroxysteroid dehydrogenase (type 1 17-HSD) enzyme protein and mRNA, and 17-HSD activity in human granulosa cells. The cells were obtained from patients taking part in an in vitro fertilization programme. The cells from each patient were divided into two groups: cells obtained from preovulatory follicles (LGC = granulosa cells from large follicles > or = 18 mm in diameter), and cells from other visible follicles (SGC = granulosa cells from small follicles, less than 15 mm in diameter). The identity of 17-HSD enzyme protein expressed in human granulosa cells with placental cytosolic 17-HSD (type 1 17-HSD) was assessed by immunoblot analysis using polyclonal antibodies, and the enzyme was immunolocalized in the cytoplasm of granulosa cells. Type 1 17-HSD protein concentration, 17-HSD and cytochrome P450 aromatase (P450arom) activities and oestradiol (OE2) production in cells from LGC were significantly lower than the corresponding values obtained in SGC in the same patient (paired t-test). The type 1 17-HSD protein concentration, 17-HSD activity and P450arom activity were 140 +/- 16% (mean +/- S.E.M.), 121 +/- 22% and 113 +/- 26% higher in cells from SGC, which was also reflected in a 70 +/- 12% higher OE2 production in these cells. In freshly isolated cells from LGC or SGC, a high correlation between 17-HSD and P450arom activities was observed (r = 0.93, P < 0.001). In long-term cultured cells, type 1 17-HSD was stably expressed at least until day 9, while P450arom expression decreased. In addition, treatments with gonadotrophins did not affect type 1 17-HSD protein concentration and 17-HSD activity. In contrast to this, both P450arom activity and OE2 production were significantly increased (P < 0.05). The data, therefore, suggest that type 1 17-HSD and P450arom are expressed in parallel during the latest stages of follicular maturation but, in cultured granulosa-luteal cells, the enzymes are regulated by distinct mechanisms.
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PMID:Expression of 17 beta-hydroxysteroid dehydrogenase in human granulosa cells: correlation with follicular size, cytochrome P450 aromatase activity and oestradiol production. 752 28

The isozymes of the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) gene family are responsible for the formation of the 17 beta-hydroxysteroids delta 5-androstene-3 beta,17 beta-diol, testosterone, 17 beta-estradiol, and dihydrotestosterone from their corresponding 17-ketosteroid precursors, thus playing a pivotal role in the formation of active sex steroids in both steroidogenic and peripheral target tissues. To clone the type II 17 beta-HSD gene, the full-length cDNA type II 17 beta-HSD was used as probe to screen a human leukocyte genomic DNA library. The type II 17 beta-HSD gene contains seven exons and spans > 40 kbp. The type II 17 beta-HSD gene encodes two alternatively spliced mRNAs that give rise to the previously identified type IIA 17 beta-HSD protein of 387 amino acids, as well as to a related 291-amino-acid type IIB 17 beta-HSD protein of unknown function. RNA blot analysis revealed the presence of a major 1.45-kb transcript that is abundant in placenta and endometrium. The mRNA cap site has been localized in a region between 179 and 167 nucleotides upstream of the ATG start codon by RNase protection and S1 nuclease mapping analyses. Cloning of the 17 beta-HSD type II gene provides us with the tools to study its transcriptional expression.
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PMID:The human type II 17 beta-hydroxysteroid dehydrogenase gene encodes two alternatively spliced mRNA species. 754 91

11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the conversion of cortisol to cortisone and corticosterone to 11-dehydrocorticosterone. This activity may be required to confer normal ligand specificity upon the mineralocorticoid receptor. Although an isozyme of 11-HSD was previously isolated from rat liver, a different isozyme is apparently expressed in mineralocorticoid target tissues. We isolated a sheep kidney cDNA clone encoding this isozyme by expression screening using Xenopus oocytes. The cDNA is 1.8 kb in length and encodes a protein of 427 amino acid residues with a predicted M(r) of 46,700. When expressed in oocytes, this enzyme functions as an NAD(+)-dependent 11 beta-hydrogenase with very high affinity for steroids, but it has no detectable reductase activity. It is 37% identical in amino acid sequence to an NAD(+)-dependent isozyme of 17 beta-hydroxysteroid dehydrogenase, but only 20% identical to the NADP(+)-dependent liver isozyme of 11-HSD. It is expressed at high levels in the kidney and adrenal and at lower levels in the colon. The corresponding gene is present in a single copy in the sheep genome. In humans, this gene is a candidate locus for the syndrome of apparent mineralocorticoid excess, a form of hypertension postulated to result from 11-HSD deficiency in mineralocorticoid target tissues.
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PMID:Cloning of cDNA encoding an NAD(+)-dependent isoform of 11 beta-hydroxysteroid dehydrogenase in sheep kidney. 758 2

The enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) catalyzes the 17 beta-oxidation/reduction of C18- and C19-steroids in a variety of tissues. Three human genes encoding isozymes of 17 beta-HSD, designated 17 beta-HSD types 1, 2 and 3 have been cloned. 17 beta-HSD type 1 (also referred to as estradiol 17 beta-dehydrogenase) catalyzes the conversion of estrone to estradiol, primarily in the ovary and placenta. The 17 beta-HSD type 2 is expressed to high levels in the liver, secretory endometrium and placenta. The type 2 isozyme catalyzes the oxidation of androgens and estrogens equally efficiently. Also, the enzyme possesses 20 alpha-HSD activity demonstrated by its ability to convert 20 alpha-dihydroprogesterone to progesterone. Testicular 17 beta-HSD type 3 catalyzes the conversion of androstenedione to testosterone, dehydroepiandrosterone to 5-androstenediol and estrone to estradiol. The 17 beta-HSD3 gene is mutated in male pseudohermaphrodites with the genetic disease 17 beta-HSD deficiency.
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PMID:The molecular biology of androgenic 17 beta-hydroxysteroid dehydrogenases. 762 83

Using different hormone-dependent (MCF-7, T-47D) and hormone-independent (MDA-MB-231, Hs-578S, MDA-MB-436) human breast cancer cells, the interconversion estrone (E1)<-->estradiol (E2) was explored. The data show very clearly that in the hormone-dependent cells the tendency is to form E2 after incubation with E1, whereas after incubation with E2 most of this estrogen remains unchanged. In the hormone-independent cells, in contrast most of E1 remains E1, while E2 is converted into E1. The tendency of the reductive<-->oxidative direction is supported by the analysis of estrogens in the culture medium. To explore the possible action of different drugs on the 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity, it was observed that the potent antiestrogen ICI 164,384 inhibits the conversion of E1 to E2, while a lesser effect is observed with Danazol and only weak inhibition is obtained with the progestagen Promegestone (R-5020). It is concluded that the orientation of 17 beta-HSD activity for the interconversion E1<-->E2 in hormone-dependent and -independent cells is related to the hormonal status of the cells.
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PMID:Transformation of estrone and estradiol in hormone-dependent and hormone-independent human breast cancer cells. Effects of the antiestrogen ICI 164,384, danazol, and promegestone (R-5020). 764 31


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