SEARCH · PubMed Health

Results for “Progesterone Reductase”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources

PubMed1994

Over-expression of human type I (placental) 3 beta-hydroxy-5-ene-steroid dehydrogenase/isomerase in insect cells infected with recombinant baculovirus.

Human type I placental 3 beta-hydroxy-5-ene-steroid dehydrogenase/steroid 5-->4-ene-isomerase (3 beta-HSD/isomerase) synthesizes androstenedione from fetal dehydroepiandrosterone and progesterone from pregnenolone. The full length cDNA that encodes type I 3 beta-HSD/isomerase was inserted into the baculovirus, Autographa californica multiple nucleocapsid polyhedrosis virus, and expressed in Spodoptera fungiperda (Sf-9) insect cells. Western blots showed that the baculovirus-infected Sf-9 cells produced an immunoreactive protein that co-migrated with purified placental 3 beta-HSD/isomerase. Ultracentrifugation localized the expressed enzyme activities in all the membrane-associated organelles of the Sf-9 cell (nuclear, mitochondrial and microsomal). Kinetic studies showed that the expressed enzyme has 3 beta-HSD and isomerase activities. The Michaelis-Menton constant is very similar for the 3 beta-HSD substrate, 5 alpha-androstan-3 beta- ol-17-one, in the Sf-9 cell homogenate (Km = 17.9 microM) and placental microsomes (Km = 16.7 microM). The 3 beta-HSD activity (Vmax = 14.5 nmol/min/mg) is 1.6-fold higher in the Sf-9 cell homogenate compared to placental microsomes (Vmax = 9.1 nmol/min/mg). The Km values are almost identical for the isomerase substrate, 5-androstene-3,17-dione, in the Sf-9 cell homogenate (Km = 14.7 microM) and placental microsomes (Km = 14.4 microM). The specific isomerase activity is 1.5-fold higher in the Sf-9 cells (Vmax = 25.7 nmol/min/mg) relative to placenta (Vmax = 17.2 nmol/min/mg). These studies show that our recombinant baculovirus system over-expresses fully active enzyme that is kinetically identical to native 3 beta-HSD/isomerase in human placenta.

Animals↗

PubMed1995

Organization of 3 beta-hydroxysteroid dehydrogenase/isomerase and cytochrome P450scc into a catalytically active molecular complex in bovine adrenocortical mitochondria.

We have previously reported the co-localization [Cherradi et al., Endocrinology 134 (1994) 1358-1364] of 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) and cytochrome P450scc (cyt. P450scc) in the inner membrane and in the intermembrane contact sites of adrenocortical mitochondria. This observation raises the question of a possible functional association between the two proteins. Isolated bovine adrenocortical mitochondria are able to convert cholesterol to progesterone without the need of exogenous cofactors. An association of 3 beta-HSD and cyt. P450scc is observed during the purification of 3 beta-HSD from mitochondria. The behaviour of 3 beta-HSD on a column of Heparin-Sepharose is modified by the presence of cyt. P450scc. Immunoprecipitations from mitochondria with either anti-cyt. P450scc or anti 3 beta-HSD antibodies result in a co-precipitation of the two proteins. Both proteins engaged in these immunocomplexes are catalytically active. The interaction was further demonstrated by the surface plasmon resonance method using purified components. An affinity demonstrated by the surface plasmon resonance method using purified components. An affinity constant of 0.12 microM between 3 beta-HSD and P450scc was obtained. These observations suggest that P450scc and 3 beta-HSD may associate into a molecular complex in the mitochondrial compartment and may constitute a functional steroidogenic unit, thus opening new possibilities in the regulation of the production of progesterone and its flow in the adrenocortical cell.

3-Hydroxysteroid Dehydrogenases↗

PubMed1996

Differential effects of trilostane and cyanoketone on the 3 beta-hydroxysteroid dehydrogenase-isomerase reactions in androgen and 16-androstene biosynthetic pathways in the pig testis.

3 beta-Hydroxysteroid dehydrogenase-isomerase (3 beta-HSD-I) activity in the pig testis is responsible for the conversion of dehydroepiandrosterone (DHA) to 4-androstenedione and also for the conversion of 5,16-androstadien-3 beta-ol (andien-beta) to 4, 16-androstadien-3-one (dienone). Therefore, 3 beta-HSD-I plays an essential role in the biosynthesis of hormonally and pheromonally active steroids. Previous studies from this laboratory have suggested that the 3 beta-HSD-I reactions in the androgen and 16-androstene biosynthetic pathways may be catalysed by different enzymes with selective substrate specificities [3, 4]. The aim of the present studies was to investigate the reactions further by examining the effects of two classical steroidal inhibitors of 3 beta-HSD-I, trilostane (WIN 24540) and cyanoketone (WIN 19578), on the kinetic parameters of the 3 beta-HSD-I reactions in immature (< 3 weeks) pig testis microsomes. In kinetic analyses of the conversion of DHA to 4-androstenedione, both trilostane and cyanoketone caused increases in the Km(app) for DHA which at the highest concentration used, were 15-fold the control Km(app) of 1.4 mumol/l. No effect on the Vmax(app) (6.55 +/- 0.74 nmol/h/mg protein) was observed, demonstrating that competitive inhibition was evident. Slope and intercept replots confirmed the competitive nature of the inhibition and Ki(app) values of 0.16 mumol/l for trilostane and 0.20 mumol/l for cyanoketone were respectively 9 and 7-fold lower than the Km(app) value. In contrast, trilostane and cyanoketone had no effect on the Km(app) for andien-beta (0.26 mumol/l). The Vmax(app) (1.12 nmol/h/mg protein) was decreased by 40-50% only by trilostane at the highest concentration used, demonstrating a very low affinity for the andien-beta active site. Ki(app) values for trilostane and cyanoketone, obtained from slope and intercept replots were, respectively 1.1 and 1.6 mumol/l, which were 4 and 6-fold greater than the Km(app) for andien-beta. Therefore, trilostane and cyanoketone were powerful competitive inhibitors of the conversion of DHA to 4-androstenedione but were weak non-competitive inhibitors of the conversion of andien-beta to dienone. The selective effects of trilostane and cyanoketone on the 3 beta-HSD-Is involved in the androgen and 16-androstene biosynthetic pathways strongly suggest that the reactions are catalysed by separate enzymes, or at least separate, non-interacting active sites on a single enzyme.

Androstadienes↗

PubMed2004

Identification of 3beta,5beta-tetrahydroprogesterone, a progesterone metabolite, and its stimulatory action on preoptic neurons in the avian brain.

We have demonstrated recently that the quail brain possesses the cholesterol side-chain cleavage enzyme (cytochrome P450scc) and 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3beta-HSD) and produces pregnenolone, pregnenolone sulfate and progesterone from cholesterol. The present study was therefore conducted to investigate progesterone metabolism in the brain of adult male quails. Employing biochemical techniques combined with HPLC and TLC analyses, the conversion of progesterone to 3beta,5beta-tetrahydroprogesterone (3beta,5beta-THP) via 5beta-dihydroprogesterone (5beta-DHP) was found in the brain. There was a clear regional difference in progesterone metabolism. The formation of 3beta,5beta-THP was high in the diencephalon and cerebrum and low in the cerebellum. Based on such a region-dependent formation of 3beta,5beta-THP, the action of this progesterone metabolite on preoptic neurons in the diencephalon was then investigated electrophysiologically using a brain slice preparation of the adult male. 3beta,5beta-THP significantly increased, in a dose-related way, the spontaneous firing activity of subsets of preoptic neurons. The stimulatory effect of 3beta,5beta-THP was greater than that of progesterone and its threshold concentration ranged between 10(-6) and 3x10(-6) M. In 33% of cells in the preoptic area, however, 3beta,5beta-THP did not change the spontaneous firing activity even at the high concentration, 10(-5) M. Because preoptic neurons are considered to be involved in the regulation of a variety of male reproductive behaviors, 3beta,5beta-THP may regulate some reproductive behavior through the mechanism that provokes such a stimulation.

Action Potentials↗

PubMed2026

Genome-wide identification and expression profiling of HSD3B and SDR42E1 genes in the Pacific oyster (Crassostrea gigas): potential associations with gonadal development.

Sex steroids are lipid-soluble signaling molecules that regulate sex differentiation, reproductive development and physiological homeostasis in animals. 3β-Hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) is a key steroidogenic enzyme, whereas SDR42E1, an extended short-chain dehydrogenase/reductase, has been implicated in sterol- and steroid-related metabolism. However, the composition, evolutionary relationships and expression patterns of the HSD3B- and SDR42E1-related genes in bivalve gonadal development remain poorly characterized. In this study, five PF01073-containing genes, comprising three CgHsd3b and two CgSdr42e1 genes, were identified in the Pacific oyster Crassostrea gigas. Phylogenetic analysis separated the proteins into HSD3B-related and SDR42E1-related groups, and gene-structure and motif analyses indicated subfamily-level divergence. All five proteins retained the SDR domain but differed in exon-intron structure and motif composition. Each contained the extended-SDR TGxxGxxG motif, whereas exact classical [ST]GxxxGxG and NNAG motifs were absent. Tyr- and Lys-equivalent residues were conserved, while the HSD3B1 Ser-equivalent position contained Thr in two C. gigas proteins and Ser in one. These features support their classification as extended-SDR proteins but do not establish enzymatic activity or substrate specificity. The three CgHsd3b genes were dispersed on one chromosome, whereas CgSdr42e1-1 and CgSdr42e1-2 were adjacent on another chromosome, suggesting a possible local duplication event for the CgSdr42e1 pair. Public RNA-seq data showed distinct tissue- and gonadal-stage expression patterns, with several genes displaying gonad-biased or female-stage-associated expression. Independent RT-qPCR profiling of the representative genes CgHsd3b-3 and CgSdr42e1-1 detected stage-dependent expression, although tissue rankings differed from those in the public RNA-seq datasets. These differences may reflect the use of independent biological samples, tissue composition, normalization procedures, and platform-specific measurements. Because enzymatic assays, metabolite measurements, cellular localization, and functional perturbation were not performed, the results identify candidate genes whose expression is associated with gonadal development rather than demonstrating regulatory roles. This study provides a comparative framework for future functional investigation of sterol- and steroid-related metabolism in bivalves.

Animals↗

PubMed2005

Characterization of the guinea pig 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4-isomerase expressed in the adrenal gland and gonads.

The guinea pig adrenal gland, analogous to the human, possesses the capacity to synthesize C(19) steroids. In order to further understand the control of guinea pig adrenal steroidogenesis we undertook the characterization of the guinea pig 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase (3beta-HSD) expressed in the adrenal gland. A cDNA clone encoding guinea pig 3beta-HSD isolated from a guinea pig adrenal library is predicted to encode a protein of 373 amino acid residues and 41,475Da. Ribonuclease protection assay suggests that this cDNA corresponds to the predominant, if not the sole, mRNA species detectable in total RNA from the guinea pig adrenal gland, ovary and testis. The guinea pig 3beta-HSD shows a similar affinity for both pregnenolone and dehydroepiandrosterone, and in addition, a 17beta-HSD type II-like activity was also observed. A phylogenetical analysis of the 3beta-HSD gene family demonstrates that the guinea pig is in a parallel branch to the myomorpha group supporting the hypothesis that the guinea pig lineage has branched off after the divergence among primates, artiodactyls and rodents, suggesting the paraphyly of the order rodentia.

Adrenal Glands↗

PubMed2006

Rational proteomics V: structure-based mutagenesis has revealed key residues responsible for substrate recognition and catalysis by the dehydrogenase and isomerase activities in human 3beta-hydroxysteroid dehydrogenase/isomerase type 1.

Mammalian 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) is a member of the short chain dehydrogenase/reductase. It is a key steroidogenic enzyme that catalyzes the first step of the multienzyme pathway conversion of circulating dehydroepiandrosterone and pregnenolone to active steroid hormones. A three dimensional model of a ternary complex of human 3beta-HSD type 1 (3beta-HSD_1) with an NAD cofactor and androstenedione product has been developed based upon X-ray structures of the ternary complex of E. coli UDP-galactose 4-epimerase (UDPGE) with an NAD cofactor and substrate (PDB_AC: 1NAH) and the ternary complex of human type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD_1) with an NADP cofactor and androstenedione (PDB_AC: 1QYX). The dimeric structure of the enzyme was built from two monomer models of 3beta-HSD_1 by respective 3D superposition with A and B subunits of the dimeric structure of Streptococcus suis DTDP-D-glucose 4,6-dehydratase (PDB_AC: 1KEP). The 3D model structure of 3beta-HSD_1 has been successfully used for the rational design of mutagenic experiments to further elucidate the key substrate binding residues in the active site as well as the basis for dual function of the 3beta-HSD_1 enzyme. The structure based mutant enzymes, Asn100Ser, Asn100Ala, Glu126Leu, His232Ala, Ser322Ala and Asn323Leu, have been constructed and functionally characterized. The mutagenic experiments have confirmed the predicted roles of the His232 and Asn323 residues in recognition of the 17-keto group of the substrate and identified Asn100 and Glu126 residues as key residues that participate for the dehydrogenase and isomerization reactions, respectively.

Amino Acid Sequence↗

PubMed2005

Effects of ciprofibrate on testicular and adrenal steroidogenic enzymes in the rat.

Testicular and adrenal steroidogenic enzymes were measured radiometrically following oral dosing of rats with ciprofibrate (2-[4-(2,2-dichlorocyclopropyl) phenoxyl]-2-methylpropinoic acid), a peroxisome proliferator. Six-week-old male Fisher 344 rats were fed a diet containing ciprofibrate (0.025%, w/w) for 3, 7, 14, 28, 56, 84, 112 or 140 days leading to a daily ciprofibrate intake of approximately 15 mg/kg body weight/day. Ciprofibrate caused a marked inhibition of testicular 3beta-hydroxysteroid dehydrogenase-isomerase (3beta-HSD) activity that was significant after 3 days and subsequently decreased to 40% of control level. Ciprofibrate treatment also reduced 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity to a lesser extent but had no effect on 17-hydroxylase (17-OHase) activity. Immunoblot analyses indicated that ciprofibrate treatment did not alter enzyme protein levels and semi-quantitative RT-PCR analysis also revealed no significant changes in testicular 3beta-HSD mRNA levels. Furthermore, in addition to the enzyme-specific effect of ciprofibrate on 3beta-HSD in the testes, a tissue-specific effect was also evident, since no significant effects of ciprofibrate were seen on the activities of 3beta-HSD or 21-OHase in the adrenal glands from the same animals.

17-Hydroxysteroid Dehydrogenases↗

PubMed2005

Chloride efflux in unstimulated Leydig cells causes autonomous cAMP production and stimulatory/inhibitory steroidogenesis with an efflux inhibitor.

Gonadotropins cause immediate chloride secretion in Leydig cells, which still have an unknown physiological. Thyroid and Leydig cells produce more cAMP and steroids, respectively, under low or chloride-free conditions. Here, we show that chloride efflux mediated by incubation of Mouse Leydig Tumor cells (MLTC-1) in hypotonic or chloride-free isotonic buffers results in more cAMP production without any gonadotropic stimulation. MLTC-1 cells incubated with 0.5mM diphenylamine-2-carboxylate (DPC), a chloride efflux inhibitor, produced increased amounts of testosterone as chloride ions were substituted by gluconate or sulphate ions under isotonic conditions. There was also an up-regulation of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase/isomerase type I mRNAs, without human chorionic gonadotropin. With the exception of cAMP production, 2mM DPC inhibited all of the above, including the transcription of constitutively expressed cholesterol side-chain cleavage enzyme and the L19 house-keeping gene. Although it was speculated that gonadotropin mediated chloride secretion could aid steroid hormone release, we conclude that the real reason for chloride secretion in Leydig cells may be to "kick start" cAMP production.

Animals↗

PubMed2006

Activities of 3beta-HSD and aromatase in slices of developing and adult zebra finch brain.

Sex steroids influence the development and function of the songbird brain. Developmentally, the neural circuitry underlying song undergoes masculine differentiation under the influence of estradiol. In adults, estradiol stimulates song behavior and the seasonal growth of song control circuits. There is good reason to believe that these neuroactive estrogens are synthesized in the brain. At all ages, estrogens could act at the lateral ventricle, during migration, or where song nuclei exist or will form. We investigated the activity of two critical steroidogenic enzymes, 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) and aromatase, using a slice culture system. Sagittal brain slices were collected from juvenile (posthatch day 20) and adult zebra finches containing either the lateral ventricle, where neurons are born, or the telencephalic song nuclei HVC and RA. The slices were incubated with (3)H-dehydroepiandrosterone or (3)H-androstenedione. Activity was determined by isolating certain products of 3beta-HSD (5alpha-androstanedione, 5beta-androstanedione, estrone, and estradiol) and aromatase (estrone and estradiol). Activities of both 3beta-HSD and aromatase were detected in all slices and were confirmed using specific enzyme inhibitors. We found no significant difference in activity between adult males and females in either region for either enzyme. Juvenile female slices containing the lateral ventricle, however, showed greater levels of 3beta-HSD activity than did similar slices from age-matched males. Determination of the activity of these critical steroidogenic enzymes in slice culture has implications for the role of neurosteroids in brain development.

3-Hydroxysteroid Dehydrogenases↗

PubMed1981

Acquired adrenal hyperplasia: with special reference to 3 beta-hydroxysteroid dehydrogenase.

Acquired virilism in adult females amy be due to a number of primary disorder of the adrenal or the ovary, or both. In this review, HSD deficiency has been presented as one distinct cause. Its diagnosis as described in the report by Rosenfield and his co-workers depends upon several features. The urinary pattern of delta 5-3 beta-ol metabolites should be typical of that of congenital HSD deficiency. The excretion of pregnenetriol as compared with pregnanetriol (although the latter is usually high) should show a preponderance of the former. The elevation of 16-hydroxy compounds in the urine is also characteristic. The plasma steroids having the delta 5-3 beta-ol configuration should be elevated to an extent not seen in any other disorder except with an adrenal tumor. Specifically, plasma 17-hydroxypregnenolone levels will be extremely elevated, as will DHEA and the DHEAS levels. In the initial stage of diagnosis, one might initiate the work-up by determining the plasma DHEA and DHEAS concentrations so that, when these are distinctly elevated, one may proceed to further study. In the extremely mild forms it will probably be necessary to apply adrenal stimulation with ACTH in order to bring the abnormal pattern into perspective.

3-Hydroxysteroid Dehydrogenases↗

PubMed1988

Ketoconazole inhibits multiple steroidogenic enzymes involved in androgen biosynthesis in the human ovary.

Ketoconazole (KZ) has been shown to inhibit testicular and adrenal steroidogenesis and is useful in the medical management of gonadotropin-independent precocious puberty, prostatic cancer, and Cushing's syndrome. To determine whether KZ similarly affects ovarian steroidogenesis, the authors examined its effect on the activity of the human ovarian 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD), 17-hydroxylase (17-OH), and aromatase (AR) in vitro. A dose-dependent decrease in the activities of 3 beta-HSD and 17-OH was observed with increasing amounts of KZ. With 10, 50, and 100-fold excess KZ, the activity of 3 beta-HSD decreased by 59% (P less than 0.001), 73% (P less than 0.005), and 85% (P less than 0.005), respectively. At equimolar concentrations with substrate (50 microM), KZ inhibited 17-OH by 70% (P less than 0.01). No significant effect on ovarian AR activity was observed, except at the highest concentration of KZ tested. The authors conclude that low concentrations of KZ profoundly inhibit the activity of human ovarian 3 beta-HSD and 17-OH in vitro. These observations suggest that KZ might be useful in the medical management of women with hyperandrogenism, but further experimentation and clinical trials will be necessary.

3-Hydroxysteroid Dehydrogenases↗

PubMed2002

Thyroid hormone-induced protein (TIP) gene expression by 3,5,3(')-triiodothyronine in the ovarian follicle of perch (Anabas testudineus, Bloch): modulation of 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase enzyme by TIP.

Our previous reports had shown that 3,5,3'-triiodothyronine (T(3)) induced the generation of a 52-kDa monomer protein, i.e., TIP (thyroid hormone-induced protein) in the perch ovarian follicle. TIP, in turn, increased progesterone formation by stimulating Delta(5)-3beta-HSD activity (3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase) [Eur. J. Endocrinol. 134 (1996) 128-135; Gen. Comp. Endocrinol. 113 (1999) 212-220]. In the present investigation, perch ovarian follicles were incubated in the absence (control) or the presence of T(3) or gonadotropin (GTH) or human chorionic gonadotropin (hCG). RNAs were isolated and allowed to hybridize with a radiolabeled TIP oligonucleotide probe prepared on the basis of the N-terminal 17-amino-acid sequence of TIP. Only RNA from T(3)-incubated follicles hybridized with the probe, while RNA from control or GTH- or hCG-incubated follicles did not hybridize with the probe. The transcript size of TIP mRNA was approximately 1.8 kb. mRNA isolated from T(3)-incubated ovarian follicles subjected to in vitro translation and Western blot analysis clearly identified a 52-kDa protein which was not found with the mRNA from the control follicles. However, both TIP and GTH stimulated progesterone secretion from perch ovarian follicles in vitro. GTH stimulation of Delta(5)-3beta-HSD was due to the stimulation of enzyme protein synthesis as a more than twofold increase in Delta(5)-3beta-HSD occurred in response to GTH. But TIP did not stimulate synthesis of Delta(5)-3beta-HSD protein. However, in vitro incubation of Delta(5)-3beta-HSD enzyme with TIP in the presence of NAD and substrate (pregnenolone) greatly stimulated enzyme activity, while incubation with GTH had no effect, indicating a modulation of Delta(5)-3beta-HSD protein from a less active to a more active state by TIP. This has been supported by another observation, in which TIP (52 kDa) and Delta(5)-3beta-HSD (45 kDa) incubation resulted in a complex of 99 kDa. This suggests a protein-protein interaction in the process of Delta(5)-3beta-HSD activation by TIP. The present work, therefore, shows some new and interesting aspects of thyroid hormone regulation of the reproductive control mechanism.

Animals↗

PubMed2003

Luteal development and progesterone levels during pregnancy of the viviparous temperate lizard Barisia imbricata imbricata (Reptilia: Anguidae).

The relationship between plasma progesterone (P(4)) levels and the formation and degeneration of the corpus luteum (CL) was assessed monthly during gestation of the viviparous lizard Barisia imbricata imbricata. Histochemical activity of the delta(5-4) isomerase 3 beta-hydroxysteroide dehydrogenase (delta(5-4)3beta-HSD) in the luteal tissue and embryonic development were also observed. Females were gravid throughout winter and great part of spring (late November or early December until late May or early June). Corpus luteum development occurred in the first third of gestation (December and January) when the embryo reached developmental stage 27. Four sequential stages were identified during development and three stages during regression of the CL. The follicular and thecal tissue participated in the formation of the luteal cell mass. According to Xavier's classification, the CL of B. i. imbricata is a subtype from Type III. The activity of delta(5-4)3beta-HSD was observed mainly in the luteal cell mass. The first degenerative changes in the CL were observed in the early second third of the gestation and continued gradually until parturition. Progesterone levels increased in early pregnancy and reached its highest level during January (3.07+/-1.04 ng/ml) when mature corpora lutea were present. Gradual diminution in progesterone concentrations occurred in the second and last third of pregnancy and coincided with advanced degenerative changes and diminution in histochemical activity of delta(5-4)3beta-HSD in the luteal tissue. These observations suggest that the CL is the major source of progesterone during pregnancy of B. i. imbricata.

Animals↗

PubMed1994

A new cause of progressive intrahepatic cholestasis: 3 beta-hydroxy-C27-steroid dehydrogenase/isomerase deficiency.

There have been a few reports of infants with severe neonatal cholestasis related to a defect in primary bile acid synthesis. To assess the importance of such deficiency among children with progressive intrahepatic cholestasis (Byler disease), screening for inborn errors in bile acid synthesis was performed by fast atom bombardment ionization-mass spectrometry of urine samples from 30 affected children. Bile acid analysis revealed a specific fast atom bombardment ionization-mass spectrometry profile for 3 beta-hydroxy-C27 steroid dehydrogenase/isomerase deficiency in five children who had jaundice, hepatosplenomegaly, and fatty stools beginning at ages ranging from 4 to 46 months. None of them had pruritus. Liver function tests showed persistently normal serum gamma-glutamyltransferase activity, low serum cholesterol and vitamin E levels, normal serum bile acid concentrations despite raised serum bilirubin levels, and decreased prothrombin time and clotting factor V. In four of the cases a similar disease was observed in siblings. Liver function returned to normal after oral ursodeoxycholic acid therapy. We conclude that 3 beta-hydroxy-C27-steroid dehydrogenase/isomerase deficiency should be considered when idiopathic cholestatic liver disease with clinical features akin to Byler disease is characterized by the association of normal serum gamma-glutamyltransferase activity, normal serum bile acid concentration, absence of pruritus, and a return to normal liver function during ursodeoxycholic acid therapy. Early identification of these children is essential because they benefit from bile acid therapy and might thus avoid the need for liver transplantation.

Alanine Transaminase↗

PubMed1981

Failure to detect delta 5-3 beta-hydroxysteroid oxidoreductase activity in the preimplantation rabbit embryo.

Preimplantation rabbit embryos were incubated with pregnenolone and dehydroisoandrosterone under conditions which gave formazan precipitation by the histochemical technique. The metabolic fate of the labeled steroids was assessed simultaneously. There was no concomitant transformation of pregnenolone to progesterone and dehydroisoandrosterone was not transformed to androstenedione. It is concluded that the formazan precipitation is coupled with an "activity" other than delta 5-3 beta-hydroxysteroid oxidoreductase.

3-Hydroxysteroid Dehydrogenases↗

PubMed1984

Inhibition of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity in the granulosa cells of mouse ovarian follicles by follicular fluid peptide.

A protein fraction (GF2) was purified from sheep ovarian follicular fluid. Its action on 3 beta-HSD activity in the mouse granulosa cells was measured in an in vitro system. The fraction (GF2) caused dose-dependent depletion of the 3 beta-HSD activity in granulosa cells and progesterone in the spent medium. A maximum inhibition of the activity was achieved after 30 min incubation of the granulosa cells with the GF2 fraction. Further purified HPLC fraction (Fr1) also inhibited 3 beta-HSD activity. In vivo administration of the GF2 fraction in normal cycling female mice also decreased the 3 beta-HSD activity in the granulosa cells of the ovarian follicles and plasma progesterone levels indicating the GF2 fraction to be a 3 beta-HSD inhibitor.

3-Hydroxysteroid Dehydrogenases↗

PubMed1980

Effect of exogenous hormones on the activity of delta 5,3 beta-hydroxysteroid dehydrogenase in cultured granulosa cells from proestrus and preovulatory rat ovarian follicles.

Activity of delta 5,3 beta-hydroxysteroid dehydrogenase (delta 5,3 beta-OH SD) in cultured granulosa cells isolated from rat ovarian follicles at various hours of proestrus was histochemically investigated. Control cultures as well as cultures with addition of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, and estradiol were carried on. In control cultures activity of the enzyme followed more or less the pattern observed in vivo. Exogenous LH added during preovulatory LH surge showed additive effect on enzyme activity. Other hormones stimulated enzyme activity on the morning of proestrus and at the time close to ovulation, when prolactin exerted most stimulatory effect.

3-Hydroxysteroid Dehydrogenases↗