Evidence map›Paper›PMID 25355646›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2015

Regulation of human 3β-hydroxysteroid dehydrogenase type 2 by adrenal corticosteroids and product-feedback by androstenedione in human adrenarche.

James L Thomas, Maheshinie Rajapaksha, Vance L Mack, Geneva A DeMars, Joseph A Majzoub, Himangshu S Bose

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

James L ThomasDivision of Basic Medical Sciences (J.L.T., V.L.M.) and Department of Ob-Gyn (J.L.T.), Mercer University School of Medicine, Macon, Georgia; Department of Biochemistry, Mercer University School of Medicine, Savannah, Georgia (M.R., G.A.D., H.S.B.); Memorial University Medical Center, Anderson Cancer Institute, Savannah, Georgia (H.S.B.); and Division of Endocrinology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (J.A.M.) thomas_j@mercer.edu.
Maheshinie RajapakshaDivision of Basic Medical Sciences (J.L.T., V.L.M.) and Department of Ob-Gyn (J.L.T.), Mercer University School of Medicine, Macon, Georgia; Department of Biochemistry, Mercer University School of Medicine, Savannah, Georgia (M.R., G.A.D., H.S.B.); Memorial University Medical Center, Anderson Cancer Institute, Savannah, Georgia (H.S.B.); and Division of Endocrinology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (J.A.M.).
Vance L MackDivision of Basic Medical Sciences (J.L.T., V.L.M.) and Department of Ob-Gyn (J.L.T.), Mercer University School of Medicine, Macon, Georgia; Department of Biochemistry, Mercer University School of Medicine, Savannah, Georgia (M.R., G.A.D., H.S.B.); Memorial University Medical Center, Anderson Cancer Institute, Savannah, Georgia (H.S.B.); and Division of Endocrinology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (J.A.M.).
Geneva A DeMarsDivision of Basic Medical Sciences (J.L.T., V.L.M.) and Department of Ob-Gyn (J.L.T.), Mercer University School of Medicine, Macon, Georgia; Department of Biochemistry, Mercer University School of Medicine, Savannah, Georgia (M.R., G.A.D., H.S.B.); Memorial University Medical Center, Anderson Cancer Institute, Savannah, Georgia (H.S.B.); and Division of Endocrinology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (J.A.M.).
Joseph A MajzoubDivision of Basic Medical Sciences (J.L.T., V.L.M.) and Department of Ob-Gyn (J.L.T.), Mercer University School of Medicine, Macon, Georgia; Department of Biochemistry, Mercer University School of Medicine, Savannah, Georgia (M.R., G.A.D., H.S.B.); Memorial University Medical Center, Anderson Cancer Institute, Savannah, Georgia (H.S.B.); and Division of Endocrinology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (J.A.M.).
Himangshu S BoseDivision of Basic Medical Sciences (J.L.T., V.L.M.) and Department of Ob-Gyn (J.L.T.), Mercer University School of Medicine, Macon, Georgia; Department of Biochemistry, Mercer University School of Medicine, Savannah, Georgia (M.R., G.A.D., H.S.B.); Memorial University Medical Center, Anderson Cancer Institute, Savannah, Georgia (H.S.B.); and Division of Endocrinology, Boston Children's Hospital, and Harvard Medical School, Boston, Massachusetts (J.A.M.).
Memorial Health University Medical Center · USMercer University · USBoston Children's Hospital · US

Funding

SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2M
Mechanism of action of steroidogenic acute regulatory protein (StAR)R01HD057876 · NICHD · MERCER UNIVERSITY MACON · PI BOSE, HIMANGSHU S · 2009 to 2013
$1.5M
NICHD NIH HHS HD057876NICHD NIH HHS P30 HD018655NICHD NIH HHS P30-HD18655NICHD NIH HHS R01 HD057876
6 · The paper itself

Abstract

In human adrenarche during childhood, the secretion of dehydroepiandrosterone (DHEA) from the adrenal gland increases due to its increased synthesis and/or decreased metabolism. DHEA is synthesized by 17α-hydroxylase/17,20-lyase, and is metabolized by 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2). In this study, the inhibition of purified human 3βHSD2 by the adrenal steroids, androstenedione, cortisone, and cortisol, was investigated and related to changes in secondary enzyme structure. Solubilized, purified 3βHSD2 was inhibited competitively by androstenedione with high affinity, by cortisone at lower affinity, and by cortisol only at very high, nonphysiologic levels. When purified 3βHSD2 was bound to lipid vesicles, the competitive Ki values for androstenedione and cortisone were slightly decreased, and the Ki value of cortisol was decreased 2.5-fold, although still at a nonphysiologic level. The circular dichroism spectrum that measured 3βHSD2 secondary structure was significantly altered by the binding of cortisol, but not by androstenedione and cortisone. Our import studies show that 3βHSD2 binds in the intermitochondrial space as a membrane-associated protein. Androstenedione inhibits purified 3βHSD2 at physiologic levels, but similar actions for cortisol and cortisone are not supported. In summary, our results have clarified the mechanisms for limiting the metabolism of DHEA during human adrenarche.

Indexed as

17-Hydroxysteroid DehydrogenasesAdrenal GlandsAdrenarcheAndrostenedioneCell LineCortisoneEnzyme InhibitorsFeedback, PhysiologicalHumansHydrocortisoneLiposomesMitochondriaProtein ConformationProtein TransportSolubility17-Hydroxysteroid Dehydrogenases3 (or 17)-beta-hydroxysteroid dehydrogenaseAndrostenedioneCortisoneEnzyme InhibitorsHydrocortisoneLiposomes

Identifiers

PMID25355646
PMCPMC4279106
OpenAlexW2159666746

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.