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Query: UNIPROT:P06889 (Mol)
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Pig testicular 20 beta-hydroxysteroid dehydrogenase (20 beta-HSD) has also 3 alpha- and 3 beta-HSD (3 alpha/beta-HSD) activities. The purified 20 beta-HSD preparation from neonatal pig testes could catalyze the conversion of 5 alpha-dihydrotestosterone (5 alpha-DHT) in the presence of beta-NADPH to 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol at the ratio of 4:3, and the specific 3 alpha/beta-HSD activity of 20 beta-HSD for 5 alpha-DHT was about 10 or 15 times larger than the 20 beta-HSD activities for 17 alpha-hydroxypregn-4-ene-3,20-dione (17 alpha-hydroxyprogesterone) or progesterone, respectively. The result indicates that the testicular 20 beta-HSD has high 3 alpha(axial, 3R)- and 3 beta(equatorial, 3S)-HSD activity. The testicular 20 beta-HSD could catalyze the reversible conversion of various 5 alpha- or 5 beta-dihydrosteroids which have a 3-carbonyl or 3-hydroxyl group with beta-NADP(H) as the preferred cofactor. The enzyme transferred the 4-proS hydrogen of NADPH to the 5 alpha-DHT for both 3 alpha- and 3 beta-hydroxylation and it was the same as the 20 beta-hydroxylation of 17 alpha-hydroxyprogesterone. Although the 3 alpha/beta-HSD activity has been known to be present in 3 alpha,20 beta-HSD of Streptomyces hydrogenans, the enzymological properties for 3 alpha/beta-HSD activity catalyzed by testicular 20 beta-HSD were different from the properties for 3 alpha/beta-HSD activity catalyzed by prokaryotic 3 alpha, 20 beta-HSD with respect to the specificity of the catalytic reaction and the cofactor requirement.
J Steroid Biochem Mol Biol 1991 Jun
PMID:20 beta-hydroxysteroid dehydrogenase of neonatal pig testis: 3 alpha/beta-hydroxysteroid dehydrogenase activities catalyzed by highly purified enzyme. 206 95

Ligand specificity of the type I steroid receptor is apparently conferred by the activity of 11 beta-hydroxysteroid dehydrogenase. To determine the kinetic properties of this enzyme, rat liver cDNA was expressed in cultured cells using recombinant vaccinia virus. Although this enzyme catalyzes only dehydrogenation when purified from rat liver, the recombinant enzyme obtained from cell lysates catalyzed both 11 beta-dehydrogenation of corticosterone to 11-dehydrocorticosterone and the reverse 11-oxoreduction reaction. At pH 8.5, the first order rate constant Kcat/Km for dehydrogenase activity exceeded that for reductase (63 vs. 38 min-1 x 10(-4], whereas the rate constants for the two reactions were nearly equal (48 vs. 47 min-1 x 10(-4] at pH 7.0. These results are consistent with the previously determined pH optima for these activities in liver microsomes. Removal (with glucose-6-phosphate dehydrogenase) of NADP+ produced by the reductase reaction significantly increased reductase activity. Glycyrrhetinic acid, a known inhibitor of the dehydrogenase reaction, also inhibited the reductase reaction at slightly higher concentrations (50% inhibitory concentration, less than 5 nM for dehydrogenase, 10-20 nM for reductase). Partial inhibition of glycosylation with A1-tunicamycin decreased dehydrogenase activity 50% without affecting reductase activity. The data demonstrate that a single polypeptide catalyzes both dehydrogenation and reduction, although the presence of additional enzyme forms catalyzing one or the other activity has not been ruled out.
Mol Endocrinol 1990 Dec
PMID:Expression of 11 beta-hydroxysteroid dehydrogenase using recombinant vaccinia virus. 208 84

The histochemical activities of the enzymes alcohol dehydrogenase with propanol (A-D I) and isopropanol (A-D II) as substrates, 3- beta-hydroxysteroid dehydrogenase (3 beta .OHST-D), nicotinamideadenine dinucleotide phosphate (reduced form)-tetrazolium reductase (NADPH2-TR) and glucose-6-phosphate dehydrogenase (G6P-D) were studied in the testis of 6 cats daily injected with 20 micrograms/kg of the LHRH-analogue DTRP6-DGLY-10, LHRH-ethylamide (LHRH-A Group) and 3 cats injected with saline during 67 days. A morphometric analysis was done to evaluate the activity of the enzymes, its distribution and volume fractions of the Leydig cells with every activity. A-D II displayed a significant inhibition in the Leydig cells of the LHRH-A Group. There were no changes in the activities of G6P-D, 3 beta .OHST-D and NADPH2-TR, but it was possible to disclose some reduction of the volume fraction of the Leydig cells when the first two enzymes were used as its marker. This study corroborates that A-D II is a reaction in the pathway of steroidogenesis but does not explain whether it corresponds actually to 20-22 desmolase as proposed in the work by Hardonk (1965) or to another reaction linked to the activities of the cytochromes P450.
Cell Mol Biol 1990
PMID:Effect of a luteinizing-hormone-releasing-hormone (LHRH)-analogue on the histochemistry of the secondary alcohol-dehydrogenase in the Leydig cells of the cat testis. 222 54

Both adipose and epithelial cells isolated from the mammary glands of pregnant and lactating rats show 11 beta-hydroxysteroid dehydrogenase (11-HSD) activity, as measured by conversion of corticosterone to 11-dehydrocorticosterone. Activity in adipose cells from pregnant rats is 3-fold higher than in lactating rats. Epithelial cells from pregnant rats show one-twentieth of the activity of adipose cells, and activity is lower still in epithelial cells from lactating rats. Explants incubated for 48 h extensively metabolized corticosterone to 11-dehydrocorticosterone, and to a much lesser extent to a second unknown metabolite which is found in tissue extracts but not conditioned medium. Mammary gland 11-HSD may thus constitute one of the physiological mechanisms preventing premature milk production in response to glucocorticoids.
J Steroid Biochem Mol Biol 1990 Nov 30
PMID:Epithelial and adipose cells isolated from mammary glands of pregnant and lactating rats differ in 11 beta-hydroxysteroid dehydrogenase activity. 227 36

The metabolism of [4-14C]progesterone in the parotid salivary glands of nonpregnant female, pregnant female and male rats were investigated in vitro. The metabolic activity of the male rats was significantly lower than in either of the female groups. The pregnant group was metabolically more active than the nonpregnant female group, but his differences was not statistically significant. I homogenates and soluble fractions the main metabolite was 20-alpha-hydroxy- 4-pregnen-3-one in female rats. In male rats the main metabolites were 20-alpha-hydroxy-4- pregnen-3-one and 3-alpha-hydroxy-5-alpha-pregnan-20-one in homogenates and 20-alpha-hydroxy-4- pregnen-3-one in soluble fractions. In the microsomal fractions of both sexes polar compounds predominated. The results indicated the presence of at least the following progesterone metabolizing enzymes in art parotid salivary glands; 3-alpha-, 3-beta-, 20-alpha- and 20-beta-hydroxysteroid dehydrogenase, 5-alpha-and 5-beta-steroid hydrogenase and 17-alpha-steroid hydroxylase activities. Ind the homogenates and soluble fractions of female rats 20-alpha-hydroxysteroid dehydrogenase activity was significantly higher than in males.
J Steroid Biochem Mol Biol 1990 Nov 30
PMID:Progesterone metabolism by major salivary glands of rat--II. Parotid gland. 227 46

A novel variant of 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1) mRNA was identified from the ovine liver by reverse transcription-polymerase chain reaction (RT/PCR), and was named 11 beta-HSD1C mRNA. Sequence analysis of the RT-PCR product revealed that 11 beta-HSD1C mRNA was the product of an alternative exon-splicing within the 11 beta-HSD1 gene in which exon 5 was spliced out. Although it caused a deletion of 48 amino acids in the deduced 11 beta-HSD1 protein, this alternative splicing did not result in a shift within the predicted open reading frame of 11 beta-HSD1 cDNA. Thus, 11 beta-HSD1C mRNA was predicted to code for a protein of 244 amino acids. Using RT-PCR, we also examined the expression of 11 beta-HSD1C mRNA in ovine fetal organs and in maternal myometrium, endometrium, chorion, amnion and placenta. The 11 beta-HSD1C mRNA was expressed ubiquitously, similar to 11 beta-HSD1A mRNA, but at a lower abundance. Furthermore, since levels of 11 beta-HSD1C mRNA were directly related to those of 11 beta-HSD1A mRNA, there is no tissue-specificity for this shorter transcript and the only factor regulating its production appears to be 11 beta-HSD1A mRNA itself. To determine whether 11 beta-HSD1C mRNA encoded a functional enzyme, we inserted the cDNA into the expression vector pRc/CMV, and transfected the construct into Chinese hamster ovary cells. The transfected cells expressed a mRNA of expected size but contained no detectable 11 beta-HSD activity. When combined with cellular extracts of 11 beta-HSD1A cDNA transfected cells, they also did not alter either the dehydrogenase or reductase activity. The functional significance of the 11 beta-HSD1 transcript lacking exon 5 (11 beta-HSD1C mRNA) remains to be determined.
J Steroid Biochem Mol Biol 1995 Nov
PMID:Identification and tissue distribution of a novel variant of 11 beta-hydroxysteroid dehydrogenase 1 transcript. 749 5

Mineralocorticoid receptors (MR) have equal affinity for the mineralocorticoid aldosterone, and the physiological glucocorticoids cortisol and corticosterone. In epithelial tissues in vivo, MR are protected against glucocorticoid occupancy by the enzyme 11 beta-hydroxysteroid dehydrogenase, allowing access by the lower circulating levels of the physiological mineralocorticoid aldosterone. In non-epithelial tissues, including the heart and most areas of the central nervous system, MR are not so protected, and their physiological ligand is cortisol/corticosterone. Intracerebroventricular infusion studies have shown that aldosterone occupancy of such unprotected circumventricular MR is necessary for mineralocorticoid hypertension, and the hypertensinogenic effects of peripherally infused aldosterone can be blocked by intracerebroventricular infusion of the MR antagonist RU28318. Prolonged (8 weeks) administration of mineralocorticoids to salt-loaded rats has been shown to be followed by hypertension, cardiac hypertrophy and cardiac fibrosis. Whether the hypertrophy and fibrosis reflect primary effects of aldosterone via cardiac MR, or effects secondary to occupancy of protected, epithelial MR, remains to be determined, as does the mechanism of action of salt loading in this model of mineralocorticoid hypertension.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Mineralocorticoid receptors and hypertension. 762 6

In mammals, 11 beta-hydroxysteroid dehydrogenase (11-HSD) activity allows aldosterone occupancy of mineralocorticoid receptors (MR) by inactivating endogenous glucocorticoids. The present study examined the distribution of 11-HSD2, 11-HSD1, glucocorticoid receptor (GR) and MR in kidney and brain. High levels of expression of 11-HSD2 were found in renal cortical distal tubules and more diffusely expressed in distal tubules of the medulla. No expression of 11-HSD2 was found on serial sectioning of the brain. 11-HSD1 was expressed in proximal tubules of the kidney and throughout the brain. GR mRNA was found predominantly in renal proximal tubules and diffusely in brain, while MR mRNA was located in the renal distal tubules and also in various brain nuclei. These anatomical findings support a functional relationship between 11-HSD1 and GR in both brain and kidney, but between 11-HSD2 and MR in kidney only.
Mol Cell Endocrinol 1995 Apr 28
PMID:Glucocorticoid receptor, mineralocorticoid receptors, 11 beta-hydroxysteroid dehydrogenase-1 and -2 expression in rat brain and kidney: in situ studies. 764 47

We have previously described two distinct isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) with respect to enzymatic activity in the ovine liver and kidney. To determine which isoform(s) is expressed in the ovine placenta, we studied the characteristics of 11 beta-HSD activity in placental tissues collected at days 140-143 of pregnancy. 11 beta-HSD activity was determined by a radiometric conversion assay using cortisol and cortisone as physiological substrates. At 100 nM cortisol, the placental 11 beta-HSD utilized NAD as cofactor, but displayed preference for NADP at 10 microM cortisol. Kinetic characteristics were examined in the presence of alternate cofactors, in order to determine whether this difference in the cofactor requirement represents distinct enzymes. With NAD as cofactor, the placental 11 beta-dehydrogenase had a Km (110 +/- 18 nM) compatible with the kidney enzyme, but displayed a Km (12 +/- 2 microM) similar/identical to the liver 11 beta-HSD when NADP was used. By contrast, the placental 11-oxoreductase showed preference for NADPH regardless of cortisone concentration. Kinetic analysis, using NADPH as cofactor, revealed a single species of 11-oxoreductase activity with a Km of 4 +/- 0.9 microM and a Vmax of 3.1 +/- 0.5 pmol/mg/min. Finally, since the NAD-dependent 11 beta-HSD in the ovine placenta displayed similar/identical kinetic characteristics to the enzyme described previously in the ovine kidney where a truncated 11 beta-HSD transcript was identified, we have also determined whether this transcript is expressed in the placenta by Northern blotting. It was found that the truncated 11 beta-HSD transcript was undetectable in the total RNA samples. These results demonstrate that both liver- and kidney-types of 11 beta-HSD activities are expressed in the ovine placenta, thus providing further evidence for the existence of a NAD-dependent 11 beta-HSD distinct from the well-characterized hepatic NADP-dependent enzyme. Furthermore, the lack of the truncated 11 beta-HSD transcript in the placenta suggests that the NAD-dependent enzyme identified in placenta and kidney is the product of a gene distinct from 11 beta-HSD.
J Steroid Biochem Mol Biol 1995 Apr
PMID:Co-expression of two distinct isoforms of 11 beta-hydroxysteroid dehydrogenase in the ovine placenta. 773 1

To examine the role of 11 beta-hydroxysteroid dehydrogenase 1 (11 beta-HSD1) in the control of glucocorticoid actions in the ovine pituitary during development, we have sought developmental changes in the distribution and the level of 11 beta-HSD1 mRNA by in situ hybridization. In the pars distalis, 11 beta-HSD1 mRNA was present by day 60; its amount did not change significantly until term (days 145-147) when it increased dramatically. The level of 11 beta-HSD1 mRNA increased further during the postnatal period. In contrast, 11 beta-HSD1 mRNA in the pars intermedia was not detectable until day 135; it increased in amount at days 140-143, but did not change significantly thereafter through to adulthood. We have also measured levels of both dehydrogenase and reductase activities of 11 beta-HSD1 in the pars distalis of fetal sheep at day 140 and term, and of postnatal sheep at 1-2 months of age, to determine whether changes in 11 beta-HSD1 mRNA are reflected in the levels of enzyme activities. There were progressive increases in both dehydrogenase and reductase activities from day 140 to 1-2 months postnatally, although dehydrogenase activity was consistently higher than reductase activity. Finally, we have determined the effect of short-term intrafetal cortisol infusion (5 micrograms/min for 12 h) on levels of pituitary 11 beta-HSD1 mRNA by in situ hybridization. There was no effect of cortisol infusion on 11 beta-HSD1 mRNA expression.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1995 Feb
PMID:Developmental and glucocorticoid regulation of pituitary 11 beta-hydroxysteroid dehydrogenase 1 gene expression in the ovine fetus and lamb. 777 34


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