Evidence map›Paper›PMID 24305501›Full record

ArticleAging cell2014

Combined administration of testosterone plus an ornithine decarboxylase inhibitor as a selective prostate-sparing anabolic therapy.

Ravi Jasuja, James C Costello, Rajan Singh, Vandana Gupta, Catherine S Spina, Gianluca Toraldo, Hyeran Jang, Hu Li, Carlo Serra, Wen Guo and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Aging cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

6 citing papers in PubMed, 18 citations in OpenAlex.

  1. Metabolic Messengers: testosterone.Nature metabolism · 2026
    Review
  2. Androgens and Selective Androgen Receptor Modulators to Treat Functional Limitations Associated With Aging and Chronic Disease.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023
    Review
  3. Metabolic profiling of follistatin overexpression: a novel therapeutic strategy for metabolic diseases.Diabetes, metabolic syndrome and obesity : targets and therapy · 2018
    Article
  4. Article
  5. Article
  6. 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

17 authors at 3 institutions in 1 country.

Ravi JasujaResearch Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function, Promoting Anabolic Therapies, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA.
James C Costello
Rajan Singh
Vandana Gupta
Catherine S Spina
Gianluca Toraldo
Hyeran Jang
Hu Li
Carlo Serra
Wen Guo
Pratibha Chauhan
Navjot S Narula
Tyler Guarneri
Ayla Ergun
Thomas G Travison
James J Collins
Shalender Bhasin
Brigham and Women's Hospital · USBoston University · USCharles R. Drew University of Medicine and Science · US

Funding

TUFTS--FIELDINGP30AG031679 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI SHALENDER BHASIN · 2008 to 2026
$23.9M
Mechanisms of Testosterone ActionR01AG037193 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BHASIN, SHALENDER · 2010 to 2014
$2.2M
Role of Follistatin during Androgen Regulation of Body CompositionSC1AG033407 · NIA · CHARLES R. DREW UNIVERSITY OF MED & SCI · PI SINGH, RAJAN · 2008 to 2011
$1.3M
Follistatin promotes browning and influences energy metabolismSC1AG049682 · NIA · CHARLES R. DREW UNIVERSITY OF MED & SCI · PI SINGH, RAJAN · 2014 to 2017
$1.1M
Howard Hughes Medical InstituteNIA NIH HHS 5P30AG031679NIA NIH HHS 5R01AG037193NIA NIH HHS P30 AG031679NIA NIH HHS R01 AG037193NIA NIH HHS SC1 AG033407NIA NIH HHS SC1AG033407-01A1NIA NIH HHS SC1 AG049682
6 · The paper itself

Abstract

Because of its anabolic effects on muscle, testosterone is being explored as a function-promoting anabolic therapy for functional limitations associated with aging; however, concerns about testosterone's adverse effects on prostate have inspired efforts to develop strategies that selectively increase muscle mass while sparing the prostate. Testosterone's promyogenic effects are mediated through upregulation of follistatin. We show here that the administration of recombinant follistatin (rFst) increased muscle mass in mice, but had no effect on prostate mass. Consistent with the results of rFst administration, follistatin transgenic mice with constitutively elevated follistatin levels displayed greater muscle mass than controls, but had similar prostate weights. To elucidate signaling pathways regulated differentially by testosterone and rFst in prostate and muscle, we performed microarray analysis of mRNAs from prostate and levator ani of castrated male mice treated with vehicle, testosterone, or rFst. Testosterone and rFst shared the regulation of many transcripts in levator ani; however, in prostate, 593 transcripts in several growth-promoting pathways were differentially expressed after testosterone treatment, while rFst showed a negligible effect with only 9 transcripts differentially expressed. Among pathways that were differentially responsive to testosterone in prostate, we identified ornithine decarboxylase (Odc1), an enzyme in polyamine biosynthesis, as a testosterone-responsive gene that is unresponsive to rFst. Accordingly, we administered testosterone with and without α-difluoromethylornithine (DFMO), an Odc1 inhibitor, to castrated mice. DFMO selectively blocked testosterone's effects on prostate, but did not affect testosterone's anabolic effects on muscle. Co-administration of testosterone and Odc1 inhibitor presents a novel therapeutic strategy for prostate-sparing anabolic therapy.

Indexed as

Organ Sparing TreatmentsOrnithine Decarboxylase InhibitorsAnabolic AgentsAnimalsBody WeightEflornithineEnzyme InhibitorsFollistatinHumansMaleMiceMice, Inbred C57BLMice, TransgenicMuscle, SkeletalOligonucleotide Array Sequence AnalysisOrgan SizeAnabolic AgentsEflornithineEnzyme InhibitorsFollistatinOrnithine DecarboxylaseOrnithine Decarboxylase InhibitorsRecombinant ProteinsTestosteroneaginganti-agingsarcopeniasex hormonesskeletal musclesteroids

Identifiers

PMID24305501
PMCPMC4331775
OpenAlexW1969604674

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.