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)

Delta5-3beta HSDH activity has been assayed either by spectrophotometric method or by use of radioactive substrates. The enzymatic activity is equally distributed between mitochondrial and microsomal fractions verified by electronic microscopy. The specific activity is comparable in both fractions, as well as the optimal pH and the Km for NAD and for the substrates. The delta5-3beta Hut optimal pH, specific activity and sensitivity to the inhibitory action of various steroids are different when C19 and C21 steroids are used as substrates. Estrogens and cyclic AMP have also an inhibitory action on the oxidation of C21 steroids. Treatment of microsomal or mitochondrial membranes with phospholipase A releases fatty acids (mainly arachidonic) and decreases the enzymatic activity. "Adsorbtion" of the fatty acids on bovine serum albumin partially reactivates the delta5-3beta HSDH.
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PMID:Human placental delta5-3beta hydroxysteroid dehydrogenase activity (delta5-3beta HSDH): intracellular distribution, kinetic properties, retroinhibition and influence of membrane delipidation. 0 79

Specific activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) was measured in 48 tissue specimens of human female breast cancer and, in addition, 48 nonmalignant tissue specimens obtained in each case from the same cancer-bearing breast. In all cases the nonmalignant tissue showed greater conversion of estradiol-17 beta into estrone than the neoplastic tissues. In normal human breast tissue of premenopausal women specific enzyme activity depended on the phase of the MENSTRUAL CYCLE: the highest values of 17 beta-HSD activity were found in the early secretory phase. To determine the intracellular distribution of the 17 beta-HSD, purified microsomes, mitochondria, peroxysomes, lysosomes, nuclei and cytosol fractions were prepared. The purity of each fraction was monitored by marker enzymes. It was found that the 17 beta-HSD was mainly located in mitochondria and microsomes. Furthermore it could be demonstrated that the microsomal enzyme was bound tightly to the membranes of the endoplasmic reticulum, while the mitochondrial 17 beta-HSD was mainly associated with the outer membranes of the organelle. Kinetic parameters (Km-values, coenzyme requirements and maximal velocities) of a cytoplasmic, nuclear, mitochondrial and microsomal 17 beta-HSD of normal and neoplastic human mammary tissue were compared. Maximal velocity was highest in enzyme preparations of normal mammary tissue obtained from premenopausal women in the early secretory phase. Km-values wrere nearly identical in normal and neoplastic mammary tissue preparations (approx. 1 X 10(-6) M). NAD was more efficient than NADP as a cofactor. For the conversion of estradiol to estrone the optimum temperature was approximately 40 degrees C and the optimum pH 9.5. For the reduction of estrone the optimum pH was 6.5. Sulphydryl groups were shown to be essential for catalysis.
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PMID:Comparison of the in vitro conversion of estradiol-17 beta to estrone of normal and neoplastic human breast tissue. 1 41

Detailed enzyme kinetic parameters of the reactions catalyzed by the two 17beta-hydroxysteroid dehydrogenases (17beta-HSD), which were solubilized from the microsomes of human placenta by treatment with phospholipase A, followed by enrichment and separation were determined. Both enzymes are strictly substrate specific. The most active substrate of one of the 17beta-HSD (fraction A) is estradiol-17beta, the other 17beta-HSD (fraction B) is sensitive to testosterone. Both NAD and NADP can serve as hydrogen transferring coenzymes, the latter giving about one-third of the initial rate of the former. With respect to the influence of temperature, different buffers and pH values, Michaelis constants (Km) with estradiol-17beta and testosterone as substrates, the solubilized and separated microsomal 17beta-HSD behave like those isolated from the cytoplasmic fraction. The two 17beta-HSD, after solubilization from the microsomal fraction of human placenta, enrichment and separation from each other, show only a little activity for the transfer of hydrogen between C17 of estradiol-17beta and C17 of androstenedione. On the other hand, intact microsomes and an integrated system prepared by recombination of the 17beta-enzymes by preincubation in phosphate buffer are able to catalyse very actively the transfer of hydrogen between estradiol-17beta and androstenedione. The effect of temperature and time on the recombination of the two enriched and separated microsomal enzyme activities and the determination of the pH-optimum of the hydrogen transfer reaction are described. Finally it is proposed that the hydrogen transfer between steroid hormones represents an aspect of the true reaction mechanism of steroid hormones: Steroid hormones function as hydrogen transferring coenzymes by forming part of a chain of hydrogen carriers.
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PMID:[Microsome-associated 17beta-hydroxysteroid dehydrogenases of human placenta, ii kinetic studies and characterization of the solubilized estradiol-and testosterone-"sensitive" 17beta-HSD-Activities]. 23 76

The influence of steroidal and non-steroidal antioestrogenic compounds on the effect of systemically administered oestradiol (OE2) and diethylstilboestrol (DES) was investigated in adult male rats with intact gonads. In this animal model, oestrogens induced the NADP-dependent cytoplasmic activity and prevented the inductive action of androgens on NADP-dependent microsomal activity of renal 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSDH). Simultaneous administration of tamoxifen (0.5 mg/day) with OE2 (5 microgram/day) or DES (10 microgram/day) for 10 days completely blocked the inductive effect of OE2 on cytoplasmic 3 alpha-HSDH, whereas, in the case of the microsomal enzyme, the repressive effects of OE2 and DES were antagonized only to 28 and 16% respectively. Simultaneous administration of 5 alpha-dihydrotestosterone (DHT; 0.5 mg/day) for 10 days antagonized the inductive effect of OE2 on the cytoplasmic enzyme activity to 86% and completely by-passed the repressive effects of OE2 and DES on the microsomal enzyme activity. It is concluded that oestrogenic induction of renal cytoplasmic 3 alpha-HSDH involves an oestrogen receptor mechanism which, in this animal model, can be antagonized by tamoxifen. In contrast, oestrogenic repression of renal microsomal 3 alpha-HSDH is obviously the consequence of the strong antigonadotrophic activity of oestrogens leading to subsequent repression of testicular androgen secretion by mechanisms which can be only weakly antagonized by tamoxifen. Exogenous DHT, even in the presence of OE2 or DES, completely compensates for this centrally mediated deficit of peripheral androgen.
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PMID:Action of oestrogens and antioestrogens on oestrogen-inducible cytoplasmic and androgen-inducible microsomal activity of 3 alpha-hydroxysteroid dehydrogenase in male rat kidney. 52 34

A simple procedure is described for solubilizing microsomal 3beta-hydroxysteroid dehydrogenase (3beta-HSD). Microsomes from rat adrenals or from testicular interstitial cells were incubated for 1 or 2 h at 0 C in a buffer containing NaCl followed by overnight storage at -20 C. Maximum solubilization of 3beta-hydroxy-5beta-androstan-17-one-HSD (androstane-3beta-HSD) was obtained by incubating adrenal microsomes with 1 M NaCl and interstitial cell microsomes with 2 M NaCl. Incubation with NaCl for 1 or 2 h resulted in maximum solubilization; incubation with NaCl for 4, 8 or 24 h did not change the amount of enzyme solubilized. From adrenal microsomes incubated with 1 M NaCl, up to 80% (105.7 millimicron/mg microsomes) of the total androstane-3beta-HSD activity was recovered in the supernatant following centrifugation at 130,000 x g for 1 h. The maximum amount of androstane-3beta-HSD solubilized from interstitial cell microsomes was 56% (29.5 millimicron/mg microsomes) at 2 M NaCl. The "solubilized" androstane-3beta-HSD was retarded when chromatographed on a Sephadex G-200 column and it did not pellet out when centrifuged at 130,000 x g for 15 h. KCL appeared to be equally effective in solubilizing androstane-3beta-HSD from microsomes. Other steroid dehydrogenase activities such as pregnanolone-HSD and 3beta-hydroxy-5alpha-androstan-17-one-HSD were also found in the 130,000 x g supernatant.
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PMID:A simple procedure for solubilizing 3beta-hydroxysteroid dehydrogenase from microsomes of rat adrenals and testis interstitial cells. 61 35

A binding protein which exhibits high affinity to [3H]glycyrrhetinic-acid in the rat liver microsomal fraction was solubilized with 0.2% Triton DF-18 and then purified to homogeneity. The equilibrium dissociation constant of the [3H]glycyrrhetinic-acid binding reaction and the maximal concentration for the binding of the purified protein, as determined by Scatchard plot analysis, were 27.6 nM and 7.79 nmol/mg protein, respectively. The molecular mass of the subunit (34 kDa) and 30 amino acids of N-terminal sequence of the purified protein were entirely the same as those of the reported 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). In each purification step, the recovery and purification (fold) of the glycyrrhetinic-acid binding activity corresponded to the values of 11 beta-HSD activity. These results show that the purified [3H]glycyrrhetinic-acid binding protein is 11 beta-HSD. From the molecular mass of 11 beta-HSD (135 kDa) and the maximal concentration of the binding site, it was calculated that one glycyrrhetinic acid molecule binds to one 11 beta-HSD molecule. The inhibitory effects of various glycyrrhetinic-acid derivatives on [3H]glycyrrhetinic acid binding and 11 beta-HSD activity indicate that the C30-carboxyl and C11-carbonyl groups of glycyrrhetinic acid are the principal structures for the 11 beta-HSD inhibition.
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PMID:Glycyrrhetinic acid bound to 11 beta-hydroxysteroid dehydrogenase in rat liver microsomes. 144 50

3 Alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) from Pseudomonas testosteroni was shown to reduce the xenobiotic carbonyl compound metyrapone (MPON). Reversely, MPON reductase purified from mouse liver microsomes and previously characterized as aldehyde reductase, was competitively inhibited by 3 alpha-HSD steroid substrates. For MPON reduction both enzymes can use either NADH or NADPH as co-substrate. Immunoblot analysis after native and SDS gel electrophoresis of 3 alpha-HSD gave a specific crossreaction with the antibodies against the microsomal mouse liver MPON reductase pointing to structural homologies between these enzymes. In conclusion, there seem to exist structural as well as functional relationships between a mammalian liver aldehyde reductase and prokaryotic 3 alpha-HSD. Moreover, based on the molecular weights and the co-substrate specificities microsomal mouse liver MPON reductase and Pseudomonas 3 alpha-HSD seem to be members of the short-chain alcohol dehydrogenase family.
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PMID:Functional and immunological relationships between metyrapone reductase from mouse liver microsomes and 3 alpha-hydroxysteroid dehydrogenase from Pseudomonas testosteroni. 155 29

It is well documented that sex hormone secretion decreases as age advances. In this study, 17 alpha-hydroxylase (17hy), 20 alpha(beta)-hydroxy steroid dehydrogenase (20-HSD), C17-20 lyase, 17 beta-hydroxy steroid dehydrogenase (17 beta-HSD) and aromatase activities in ovarian tissues were examined in order to study the changes in steroid metabolism in human ovary with age. Tissues were obtained from women aged 30-81 years who had undergone gynecological laparotomy. Enzyme activities were measured by the conversion of 14C-labeled progesterone, 17 alpha-hydroxy progesterone and androstenedione to amounts of corresponding labeled products. Remarkable reduction of C17-20 lyase and 17hy activities were noticed in the ovaries obtained from the women in the premenopausal stage when the activities were compared with those from reproduct women. However, the activities of aromatase, 17 beta-HSD and 20-HSD were not changed. Further, a decrease of 17hy activities was observed in the ovaries obtained from menopausal women. Aromatase activity was also reduced at this stage while the 17 beta-HSD and 20-HSD remained unchanged. In addition, the formation of 17 alpha, 20 beta-OH-P4 from 17P4 was first demonstrated indicating that activity of 20 beta-HSD in postmenopausal ovary and found to be localized in the microsomal fraction. These result indicated that the changes of ovarian steroid enzyme activities with age were characterized by a striking reduction in C17-20 lyase and 17hy activities while 17 beta-HSD and 20-HSD activities were not impaired. Aromatase activity was found to be decreased in ovaries at menopause.
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PMID:[Changes in steroid enzyme activities with age in human ovary]. 160 71

The enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD) is thought to confer specificity on the nonselective Type I adrenocorticoid receptor by converting glucocorticoids to receptor-inactive metabolites in mineralocorticoid target tissues. S1 nuclease analyses using a rat liver 11-HSD probe demonstrated tissue-specific expression of the 5' region of the 11-HSD gene in the liver, lung, and kidney not evident in previous studies. Renal tissue contained a unique protected species which mapped to a position within the coding region, consistent with a divergence in liver and kidney protein sequences. Screening of a rat kidney cDNA library resulted in the isolation of several clones (11-HSD1B) noncolinear in their 5' regions with the liver sequence (11-HSD1A). Nucleic acid sequence analysis showed that the divergent clones code for a protein lacking a 26-amino acid NH2-terminal putative membrane-spanning signal peptide. The deletion of the leader sequence from the microsomal 11-HSD1A protein may result in a nuclear localization of the 11-HSD1B isoform. The renal 11-HSD1A and 11-HSD1B species increased coordinately during ontogeny and in parallel with the developmental surge in glucocorticoids. At least three alternate sites of polyadenylation were found to be utilized by the 11-HSD gene. Southern blot analysis showed the presence of a single gene in the rat. This study shows the expression of a kidney-specific 11-HSD isoform which may protect the Type I adrenocorticoid receptor from occupation by glucocorticoids in the nucleus of a mineralocorticoid target cell.
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PMID:Tissue-specific expression of an 11 beta-hydroxysteroid dehydrogenase with a truncated N-terminal domain. A potential mechanism for differential intracellular localization within mineralocorticoid target cells. 173 55

The Type I (mineralocorticoid) receptor has identical affinities in vitro for cortisol and aldosterone. It has been suggested that the selective role of aldosterone in regulating sodium homeostasis relies on the microsomal enzyme 11 beta-hydroxysteroid dehydrogenase (11-HSD). This enzyme converts cortisol to its inactive metabolite, cortisone, preventing cortisol from binding to the Type I receptor. We have isolated human cDNA clones encoding 11-HSD from a human testis cDNA library by hybridization with a previously isolated rat 11-HSD cDNA clone. The cDNA contains an open reading frame of 876 bases, which predicts a protein of 292 amino acids. The sequence is 77% identical at the amino acid level to rat 11-HSD cDNA. The mRNA is widely expressed, but the level of expression is highest in the liver. Hybridization of the human 11-HSD cDNA to a human-hamster hybrid cell panel localized the single corresponding HSD11 gene to chromosome 1. This gene was isolated from a chromosome 1 specific library using the cDNA as a probe. HSD11 consists of 6 exons and is at least 9 kilobases long. The data developed in this study should be applicable to the study of patients with hypertension due to apparent mineralocorticoid excess, a deficiency in 11-HSD activity.
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PMID:The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. 188 95


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