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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have correlated the concentrations of serum LH, estradiol and progesterone with the activities of 2 ovarian steroid biosynthetic enzymes during the rat estrous cycle. Ovarian 3 beta-hydroxysteroid dehydrogenase isomerase (3-beta HSD) activity decreased from 29 +/- 6 nmol/mg protein/min (mean +/- SEM) in diestrus, to 7 +/- 0.4 nmol/mg protein/min in late proestrus (p less than 0.005), and subsequently increased to 36 +/- 9 nmol/mg protein/min in metestrus (p less than 0.01). Ovarian 17-hydroxylase (17-OH) activity decreased from early to late proestrus (3.3 +/- 0.2 vs 2.2 +/- 0.2 nmol/mg protein/min, p less than 0.0025), and subsequently increased to 3.9 +/- 0.2 in metestrus (p less than 0.001). Serum LH, estradiol and progesterone peaked during proestrus, and reached a nadir during estrus. We conclude that the activities of 3-beta HSD and 17-OH in the rat ovary vary markedly during the estrous cycle. These changes may underlie the pattern of steroid secretion characteristic of this process.
Steroids 1982 Aug
PMID:Ovarian steroidogenic enzyme activities during the rat estrous cycle. 689 9

20 beta-Hydroxy-5 alpha-pregnan-3-one (HPO) is a competitive inhibitor of reduction by 3 alpha/20 beta-hydroxysteroid dehydrogenase (3 alpha/20 beta-HSD; E.C.1.1.1.53) of 17 beta-hydroxy-5 alpha-androstan-3-one (DHT; 3 alpha-activity; Ki = 4.6x10(-5)M), and of 6 beta-acetoxyprogesterone (6 beta-AP; 20 beta-activity; Ki = 4.34x10(-5)M). HPO and DHT inhibit affinity alkylation of 3 alpha/20 beta-HSD by 6 beta-bromoacetoxyprogesterone (6 beta-BAP). The facts that 1) enzyme 3 alpha-activity and 20 beta-activity are both competitively inhibited by HPO with practically identical Ki-values, 2) 6 beta-BAP is solely a 20 beta-activity substrate for 3 alpha/20 beta-HSD, 3) one mole of 6 beta-BAP reacts with one mole of 3 alpha/20 beta-HSD to simultaneously inactivate 3 alpha- and 20 beta-activity, and 4) inactivation of 3 alpha/20 beta-HSD by 6 beta-BAP is inhibited by DHT (a C19-steroid) or HPO (a C21-steroid), support the view that the same active site of 3 alpha/20 beta-HSD possesses both 3 alpha- and 20 beta-activity. Bifunctional activity at the same active site is considered for other steroid-specific enzymes in female mammalian reproductive systems.
Steroids 1980 Jan
PMID:Bifunctional enzyme activity at the same active site: competitive inhibition kinetics with 3 alpha/20 beta-hydroxysteroid dehydrogenase. 692 16

Exposure of guinea pig liver microsomes to phospholipase A2 resulted in the nearly complete loss of 17 beta-hydroxysteroid oxidoreductase (17 beta-HSD) activity, the time course of which correlated with phospholipid hydrolysis and lysolecithin formation. Lysolecithin and unsaturated fatty acids added to microsomes also inactivated 17 beta-HSD indicating that they may contribute to the inactivation by phospholipase A2. If exposure to lysolecithin and fatty acids was minimized by including serum albumin in the reaction mixture, phospholipids were rapidly hydrolyzed; but in this case the extent of 17 beta-HSD inactivation was less and the rate of loss was significantly slower. The data suggest that phospholipid hydrolysis per se results in a destabilization of 17 beta-HSD resulting in the subsequent activity loss. The inactivation of 17 beta-HSD by lysolecithin and fatty acids has not been reported previously and is suggestive of a possible control mechanism in vivo.
Steroids 1980 Jul
PMID:Phospholipase A2 inactivation of microsomal 17 beta-hydroxysteroid oxidoreductase: rates of phospholipid hydrolysis and enzyme inactivation, effects of hydrolysis products and properties of the phospholipase A2-treated enzyme. 693 6

Incubation of 3 alpha, 20 beta-hydroxysteroid dehydrogenase (3 alpha, 20 beta-HSD; E.C.1.1.1.53) with the nucleoside 5'-p-fluorosulfonylbenzoyladenosine (FSA) caused a time-dependent and irreversible loss in enzyme activity. Both 3 alpha- and 20 beta-hydroxysteroid oxidoreductase activities decreased at equal rates by a first order kinetic process (in 0.05M phosphate buffer at pH 6.0 and 25 degrees C, t1/2 = 170 min). Incubation of 3 alpha, 20 beta-HSD was quenched by addition of 2-mercaptoethanol which instantaneously reacts with the fluorosulfonyl group of FSA. The cofactor NADH protected 3 alpha, 20 beta-HSD against inactivation by FSA, in a concentration-dependent manner. However, progesterone did not protect 3 alpha, 20 beta-HSD against inactivation by FSA. Evidently, FSA causes inactivation of the enzyme by irreversibly binding to the NADH-binding region at the active site of 3 alpha, 20 beta-HSD. Both 3 alpha- and 20 beta-hydroxysteroid oxidoreductase activities disappeared at equal rates under a variety of enzyme-inactivating conditions. These results suggest that both 3 alpha- and 20 beta-activities occur at the same active site of 3 alpha, 20 beta-HSD.
Steroids 1980 Sep
PMID:Affinity labeling of 3 alpha, 20 beta-hydroxysteroid dehydrogenase with a nucleoside analog. 693 28

The soluble enzyme estradiol 17 beta-dehydrogenase (17 beta-ED) from human term placental cytosol is reported to be a stereospecific oxidoreductase for estrogen substrates. A published purification scheme (heat treatment and affinity chromatography) yielded a homogeneous protein which had the reported characteristics of pure 17 beta-ED and also had 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activity. Spectrophotometric assay when the buffer contained albumin, 8 mg/ml, masked the 20 alpha-HSD activity observed in albumin-free conditions and may explain why this bifunctional activity has gone unrecognized. In human placenta, one enzyme may catalyze stereospecific oxidation/reduction of both estrogen and progesterone.
Steroids 1980 Aug
PMID:Estradiol 17 beta-dehydrogenase and 20 alpha-hydroxysteroid dehydrogenase from human placental cytosol: one enzyme with two activities? 693 33

A direct method for determination of delta 5 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity was employed in isolated Leydig cells (LC) derived from rats on fetal day 19 (Fig) and postnatal (N) days 1, 12, 24, 34 and 45 and adults. The activity of 3 beta-HSD in the adult LC was 1.15 +/- 0.02 (mumole/microgram DNA/hr, mean +/- SEM, n = 73). Activities in the other groups, expressed as a percentage of the respective adult control, were: Fig-38%; N1-39%; N12-8%; N24-89%; N34-166%; and N45-118%. A good correlation was found between histochemical staining for 3 beta-HSD and the quantitive method employed. Using (3H)-DHA as a substrate, LC isolated from F19, N1 and N12 produced testosterone in appreciable amounts (41%, 55% and 20% of the total products respectively) whereas at advanced stages of development (N24 to adulthood) the major product was androstenedione (93 +/- 1%). These findings may be explained by the observed decrease in 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity, due to an insufficient supply of NADPH, in the older vs. earlier stages of development. This study indicates the presence of steroidogenic enzymatic activity in LC throughout development in the rat. It also provides a relatively simple in vitro model for studies of testicular regulation during development.
Steroids 1980 Dec
PMID:Developmental pattern of delta 5 3 beta-hydroxysteroid dehydrogenase activity in isolated rat Leydig cells. 693 86

NADPH-dependent 20 alpha-hydroxysteroid oxidoreductase (20 alpha-HSD; EC 1.1.1.149) from bovine fetal erythrocytes was obtained for the first time free of hemoglobin by a new 2,500-fold purification scheme. This was achieved by a sequence of calcium phosphate gel absorption, ammonium sulfate fractionation, and affinity chromatography. The present results lead us to believe that the NADPH-dependent 3 beta-hydroxysteroid oxidoreductase activity, which was co-purified with 20 alpha-activity, may originate at the active site of 20 alpha-HSD (2).
Steroids 1981 May
PMID:Purification of 20 alpha-hydroxysteroid oxidoreductase from bovine fetal erythrocytes. 694 32

The activities of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) and 5 beta-reductase were analyzed in 39 normotensive controls and 128 patients with essential hypertension. The activity of 11 beta-HSD was obtained by dividing the 24-hour urinary tetrahydrocortisone by the sum of tetrahydrocortisol (THF) and allotetrahydrocortisol (aTHF), whereas the activity of 5 beta-reductase was obtained by dividing the 24-hour urinary THF by aTHF. The activity of 5 beta-reductase was significantly lower in essential hypertensives compared with normotensive controls (P < 0.05). However, the activity of 11 beta-HSD did not differ between normotensive controls and essential hypertensives. A positive correlation between the activities of 11 beta-HSD and 5 beta-reductase was observed in essential hypertensives (r = 0.60, P < 0.01). Neither 11 beta-HSD nor 5 beta-reductase activity correlated with indices of renal mineralocorticoid receptor activation, which were assessed by determination of plasma potassium and urinary excretion of sodium as well as potassium. Taken together, these results suggest that disturbances of one of the inactivation pathways of cortisol may contribute to the pathogenesis of hypertension.
Steroids 1994 Nov
PMID:The activities of 5 beta-reductase and 11 beta-hydroxysteroid dehydrogenase in essential hypertension. 770 42

11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), by converting cortisol and corticosterone to hormonally inactive cortisone and 11-dehydrocorticosterone, respectively, is an important pre-receptor signaling pathway for the renal mineralocorticoid receptor (MR). This receptor has an equal affinity for the glucocorticoids, cortisol and corticosterone, and for the mineralocorticoid, aldosterone. In states of 11 beta-HSD deficiency such as the syndrome of apparent mineralocorticoid excess (AME) and licorice ingestion, cortisol acts as a potent mineralocorticoid. In addition to the established and cloned type I 11 beta-HSD, a second 11 beta-HSD isoform has been reported in rabbit kidney and human placenta. We have analyzed the kinetics of 11 beta-HSD activity in human kidney and compared it with the expressed human type I 11 beta-HSD cDNA. Microsomes were prepared from mid-gestational human fetal kidneys and incubated with various concentrations of cortisol (0.0125-10 microM) and NAD or NADP. Kinetic analysis revealed a high affinity (apparent Km 60 nM) isoform, the activity of which was exclusively NAD-dependent. No convincing NADP-dependent activity was seen. Similarly with cortisone as a substrate no 11-oxoreductase activity was evident. In contrast, when type I human 11 beta-HSD was ligated into the expression vector pcDNAI and transiently transfected into COS-I cells, low affinity (apparent Km 2.1 microM) NADP-dependent activity was seen. 11-Oxoreductase activity was also observed. The cloned type I human 11 beta-HSD encodes an enzyme with both low-affinity, NADP-dependent, dehydrogenase and 11-oxoreductase activities, but this activity is absent in human fetal kidney (and probably adult kidney).(ABSTRACT TRUNCATED AT 250 WORDS)
Steroids 1995 Jan
PMID:Cortisol to cortisone: glucocorticoid to mineralocorticoid. 779

11 beta-Hydroxysteroid dehydrogenase (11-HSD) catalyzes the interconversion of cortisol and cortisone. This activity is postulated to protect the type I (mineralocorticoid) receptor from excessive concentrations of cortisol, allowing aldosterone to function as a mineralocorticoid. An enzyme with 11-HSD activity was isolated from rat liver and the corresponding rat and human cDNA and genomic clones isolated. This enzyme is a member of the "short chain dehydrogenase" family. Using site-directed mutagenesis, it was demonstrated that two highly conserved residues, Tyr-179 and Lys-183, are required for enzymatic function. Elimination of the amino terminus or the two glycosylation sites also destroys enzymatic activity. This may be due to actual disruption of enzymatic function or to effects on intracellular localization or stability of the enzyme. Examination of patients with apparent mineralocorticoid excess, a syndrome of juvenile hypertension thought to represent 11-HSD deficiency, did not reveal any mutations in the gene for this enzyme. There is substantial evidence for a second 11-HSD isozyme with distinct kinetic properties that is expressed in the renal distal tubule and possibly other sites of mineralocorticoid action. Apparent mineralocorticoid excess may involve this enzyme.
Steroids 1995 Jan
PMID:Functional studies of 11 beta-hydroxysteroid dehydrogenase. 779 18


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