Evidence map›Paper›PMID 26974035›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2016

Impaired 17,20-Lyase Activity in Male Mice Lacking Cytochrome b5 in Leydig Cells.

Varun Sondhi, Bryn M Owen, Jiayan Liu, Robert Chomic, Steven A Kliewer, Beverly A Hughes, Wiebke Arlt, David J Mangelsdorf, Richard J Auchus

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular endocrinology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

8 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
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  6. Expression, purification, and functional reconstitution ofBiochimica et biophysica acta. Biomembranes · 2020
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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

9 authors at 5 institutions in 2 countries.

Varun SondhiDepartments of Pharmacology (V.S., B.M.O., S.A.K., D.J.M.) and Molecular Biology (S.A.K.) and the Howard Hughes Medical Institute (D.J.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Departments of Internal Medicine and Pharmacology (J.L., R.J.A.) and the Michigan Metabolomics and Obesity Center (R.C.), University of Michigan, Ann Arbor, Michigan 48109; and the Institute of Metabolism and Systems Research (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom.
Bryn M OwenDepartments of Pharmacology (V.S., B.M.O., S.A.K., D.J.M.) and Molecular Biology (S.A.K.) and the Howard Hughes Medical Institute (D.J.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Departments of Internal Medicine and Pharmacology (J.L., R.J.A.) and the Michigan Metabolomics and Obesity Center (R.C.), University of Michigan, Ann Arbor, Michigan 48109; and the Institute of Metabolism and Systems Research (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom.
Jiayan LiuDepartments of Pharmacology (V.S., B.M.O., S.A.K., D.J.M.) and Molecular Biology (S.A.K.) and the Howard Hughes Medical Institute (D.J.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Departments of Internal Medicine and Pharmacology (J.L., R.J.A.) and the Michigan Metabolomics and Obesity Center (R.C.), University of Michigan, Ann Arbor, Michigan 48109; and the Institute of Metabolism and Systems Research (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom.
Robert ChomicDepartments of Pharmacology (V.S., B.M.O., S.A.K., D.J.M.) and Molecular Biology (S.A.K.) and the Howard Hughes Medical Institute (D.J.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Departments of Internal Medicine and Pharmacology (J.L., R.J.A.) and the Michigan Metabolomics and Obesity Center (R.C.), University of Michigan, Ann Arbor, Michigan 48109; and the Institute of Metabolism and Systems Research (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom.
Steven A KliewerDepartments of Pharmacology (V.S., B.M.O., S.A.K., D.J.M.) and Molecular Biology (S.A.K.) and the Howard Hughes Medical Institute (D.J.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Departments of Internal Medicine and Pharmacology (J.L., R.J.A.) and the Michigan Metabolomics and Obesity Center (R.C.), University of Michigan, Ann Arbor, Michigan 48109; and the Institute of Metabolism and Systems Research (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom.
Beverly A HughesDepartments of Pharmacology (V.S., B.M.O., S.A.K., D.J.M.) and Molecular Biology (S.A.K.) and the Howard Hughes Medical Institute (D.J.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Departments of Internal Medicine and Pharmacology (J.L., R.J.A.) and the Michigan Metabolomics and Obesity Center (R.C.), University of Michigan, Ann Arbor, Michigan 48109; and the Institute of Metabolism and Systems Research (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom.
Wiebke ArltDepartments of Pharmacology (V.S., B.M.O., S.A.K., D.J.M.) and Molecular Biology (S.A.K.) and the Howard Hughes Medical Institute (D.J.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Departments of Internal Medicine and Pharmacology (J.L., R.J.A.) and the Michigan Metabolomics and Obesity Center (R.C.), University of Michigan, Ann Arbor, Michigan 48109; and the Institute of Metabolism and Systems Research (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom.
David J MangelsdorfDepartments of Pharmacology (V.S., B.M.O., S.A.K., D.J.M.) and Molecular Biology (S.A.K.) and the Howard Hughes Medical Institute (D.J.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Departments of Internal Medicine and Pharmacology (J.L., R.J.A.) and the Michigan Metabolomics and Obesity Center (R.C.), University of Michigan, Ann Arbor, Michigan 48109; and the Institute of Metabolism and Systems Research (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom.
Richard J AuchusDepartments of Pharmacology (V.S., B.M.O., S.A.K., D.J.M.) and Molecular Biology (S.A.K.) and the Howard Hughes Medical Institute (D.J.M.), University of Texas Southwestern Medical Center, Dallas, Texas 75390; Departments of Internal Medicine and Pharmacology (J.L., R.J.A.) and the Michigan Metabolomics and Obesity Center (R.C.), University of Michigan, Ann Arbor, Michigan 48109; and the Institute of Metabolism and Systems Research (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom.
University of Birmingham · GBSouthwestern Medical CenterUniversity of Michigan–Ann Arbor · USHoward Hughes Medical Institute · USThe University of Texas Southwestern Medical Center · US

Funding

Pilot and Feasibility (P and F) ProgramP30DK089503 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Joyce Lee · 2010 to 2026
$20.3M
Statistics and Bioinformatics Core - WangU24DK097153 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BURANT, CHARLES F · 2012 to 2017
$10.1M
Activation of androgen biosynthesis and drug metabolism by cytochrome b5R01GM086596 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI RICHARD J. AUCHUS · 2009 to 2026
$4.8M
Howard Hughes Medical InstituteMedical Research Council 0900567Medical Research Council G0900567Medical Research Council G116/172NIDDK NIH HHS DK089503NIDDK NIH HHS P30 DK089503NIDDK NIH HHS U24 DK097153NIGMS NIH HHS R01 GM086596NIGMS NIH HHS R01GM086596Wellcome TrustWellcome Trust 105545/Z/14/Z
6 · The paper itself

Abstract

Androgen and estrogen biosynthesis in mammals requires the 17,20-lyase activity of cytochrome P450 17A1 (steroid 17-hydroxylase/17,20-lyase). Maximal 17,20-lyase activity in vitro requires the presence of cytochrome b5 (b5), and rare cases of b5 deficiency in human beings causes isolated 17,20-lyase deficiency. To study the consequences of conditional b5 removal from testicular Leydig cells in an animal model, we generated Cyb5(flox/flox):Sf1-Cre (LeyKO) mice. The LeyKO male mice had normal body weights, testis and sex organ weights, and fertility compared with littermates. Basal serum and urine steroid profiles of LeyKO males were not significantly different than littermates. In contrast, marked 17-hydroxyprogesterone accumulation (100-fold basal) and reduced testosterone synthesis (27% of littermates) were observed after human chorionic gonadotropin stimulation in LeyKO animals. Testis homogenates from LeyKO mice showed reduced 17,20-lyase activity and a 3-fold increased 17-hydroxylase to 17,20-lyase activity ratio, which were restored to normal upon addition of recombinant b5. We conclude that Leydig cell b5 is required for maximal androgen synthesis and to prevent 17-hydroxyprogesterone accumulation in the mouse testis; however, the b5-independent 17,20-lyase activity of mouse steroid 17-hydroxylase/17,20-lyase is sufficient for normal male genital development and fertility. LeyKO male mice are a good model for the biochemistry but not the physiology of isolated 17,20-lyase deficiency in human beings.

Indexed as

17-alpha-HydroxyprogesteroneAnimalsCytochromes b5FemaleFertilityLeydig CellsMaleMice, 129 StrainMice, Inbred C57BLMice, KnockoutPhenotypeSteroid 17-alpha-Hydroxylase17-alpha-HydroxyprogesteroneCytochromes b5Steroid 17-alpha-Hydroxylase

Identifiers

PMID26974035
PMCPMC4814474
OpenAlexW2302277728

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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.