Evidence map›Paper›PMID 27976414›Full record

ArticleThe Prostate2017

Low Testosterone Alters the Activity of Mouse Prostate Stem Cells.

Ye Zhou, Ben Copeland, Maya Otto-Duessel, Miaoling He, Susan Markel, Tim W Synold, Jeremy O Jones

Open access · greenAbstract read
In one paragraph

Article in The Prostate, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 32% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
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

7 authors at 1 institution in 1 country.

Ye ZhouDepartment of Cancer Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
Ben CopelandDepartment of Cancer Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
Maya Otto-DuesselDepartment of Cancer Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
Miaoling HeDepartment of Cancer Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
Susan MarkelDepartment of Cancer Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
Tim W SynoldDepartment of Cancer Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
Jeremy O JonesDepartment of Cancer Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California.
City Of Hope National Medical Center · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI XIWEI WU · 1985 to 2026
$86.3M
Ligand-Independent Selective Modulation of Androgen Receptor ActivityR00CA138711 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI JONES, JEREMY O · 2010 to 2012
$732k
NCI NIH HHS P30 CA033572NCI NIH HHS R00 CA138711
6 · The paper itself

Abstract

backgroundLow serum testosterone (low T) has been repeatedly linked to worse outcomes in men with newly diagnosed prostate cancer (PC). How low T contributes to these outcomes is unknown. Here we demonstrate that exposure to low T causes significant changes in the mouse prostate and prostate stem cells.

methodsMice were castrated and implanted with capsules to achieve castrate, normal, or sub-physiological levels of T. After 6 weeks of treatment, LC-MS/MS was used to quantify the levels of T and dihydrotestosterone (DHT) in serum and prostate tissue. FACS was used to quantify the percentages of purported prostate stem and transit amplifying (TA) cells in mouse prostates. Prostate tissues were also stained for the presence of CD68+ cells and RNA was extracted from prostate tissue or specific cell populations to measure changes in transcript levels with low T treatment.

resultsDespite having significantly different levels of T and DHT in the serum, T and DHT concentrations in prostate tissue from different T treatment groups were similar. Low T treatment resulted in significant alterations in the expression of androgen biosynthesis genes, which may be related to maintaining prostate androgen levels. Furthermore, the expression of androgen-regulated genes in the prostate was similar among all T treatment groups, demonstrating that the mouse prostate can maintain functional levels of androgens despite low serum T levels. Low T increased the frequency of prostate stem and TA cells in adult prostate tissue and caused major transcriptional changes in those cells. Gene ontology analysis suggested that low T caused inflammatory responses and immunofluorescent staining indicated that low T treatment led to the increased presence of CD68+ macrophages in prostate tissue.

conclusionsLow T alters the AR signaling axis which likely leads to maintenance of functional levels of prostate androgens. Low T also induces quantitative and qualitative changes in prostate stem cells which appear to lead to inflammatory macrophage infiltration. These changes are proposed to lead to an aggressive phenotype once cancers develop and may contribute to the poor outcomes in men with low T. Prostate 77:530-541, 2017. © 2016 Wiley Periodicals, Inc.

Indexed as

AnimalsMaleMiceMice, Inbred C57BLOrchiectomyProstateStem CellsTestosteroneTestosteroneandrogenandrogen receptorlow testosteroneprostate cancerstem cell

Identifiers

PMID27976414
PMCPMC9135143
OpenAlexW2562386099

What OpenQuestion holds

Textmetadata
LicenceTDM
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.