Evidence map›Paper›PMID 23525219›Full record

ArticleEndocrinology2013

Drug ligand-induced activation of translocator protein (TSPO) stimulates steroid production by aged brown Norway rat Leydig cells.

J Y Chung, H Chen, A Midzak, A L Burnett, V Papadopoulos, B R Zirkin

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

35 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Age-related testosterone decline: mechanisms and intervention strategies.Reproductive biology and endocrinology : RB&E · 2024
    Review
  7. Article
  8. Review
  9. Article
  10. Testicular aging, male fertility and beyond.Frontiers in endocrinology · 2022
    Review
  11. Review
  12. Article
  13. A large portion of the astrocyte proteome is dedicated to perivascular endfeet, including critical components of the electron transport chain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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 2 countries.

J Y ChungDepartment of Biochemistry and Molecular Biology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
H Chen
A Midzak
A L Burnett
V Papadopoulos
B R Zirkin
Johns Hopkins University · USMcGill University Health Centre · CAJohns Hopkins Medicine · US

Funding

Aging and Leydig Cell FunctionR37AG021092 · NIA · JOHNS HOPKINS UNIVERSITY · PI ZIRKIN, BARRY R · 2006 to 2015
$4.0M
MOLECULAR ANALYSES OF TEMPORAL BONE DEVELOPMENTR01DC003917 · NIDCD · UNIVERSITY OF PENNSYLVANIA · PI CRENSHAW, E BRYAN · 1999 to 2008
$3.3M
AGING AND LEYDIG CELL FUNCTIONR01AG021092 · NIA · JOHNS HOPKINS UNIVERSITY · PI ZIRKIN, BARRY R · 2002 to 2019
$3.1M
Androgen Regulation of Priapism in Sickle Cell DiseaseR01DK093917 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI BURNETT, ARTHUR LOUIS · 2012 to 2015
$1.6M
CIHR MOP125983NIA NIH HHS R01 AG021092NIA NIH HHS R37 AG021092NIA NIH HHS R37 AG21092NIDCD NIH HHS R01 DC003917NIDDK NIH HHS R01 DK003917NIDDK NIH HHS R01 DK093917
6 · The paper itself

Abstract

Translocator protein (TSPO; 18 kDA) is a high-affinity cholesterol-binding protein that is integrally involved in cholesterol transfer from intracellular stores into mitochondria, the rate-determining step in steroid formation. Previous studies have shown that TSPO drug ligands are able to activate steroid production by MA-10 mouse Leydig tumor cells and by mitochondria isolated from steroidogenic cells. We hypothesized herein that the direct, pharmacological activation of TSPO might induce aged Leydig cells, which are characterized by reduced T production, to produce significantly higher levels of T both in vitro and in vivo. To test this, we first examined the in vitro effects of the TSPO selective and structurally distinct drug ligands N,N-dihexyl-2-(4-fluorophenyl)indole-3-acetamide (FGIN-1-27) and benzodiazepine 4'-chlorodiazepam (Ro5-4864) on steroidogenesis by Leydig cells isolated from aged (21-24 months old) and young adult (3-6 months old) Brown Norway rats. The ligands stimulated Leydig cell T production significantly, and equivalently, in cells of both ages, an effect that was significantly inhibited by the specific TSPO inhibitor 5-androsten-3,17,19-triol (19-Atriol). Additionally, we examined the in vivo effects of administering FGIN-1-27 to young and aged rats. In both cases, serum T levels increased significantly, consistent with the in vitro results. Indeed, serum T levels in aged rats administered FGIN-1-27 were equivalent to T levels in the serum of control young rats. Taken together, these results indicate that although there are reduced amounts of TSPO in aged Leydig cells, its direct activation is able to increase T production. We suggest that this approach might serve as a therapeutic means to increase steroid levels in vivo in cases of primary hypogonadism.

Indexed as

Age FactorsAndrostenolsAnimalsBenzodiazepinonesCell Line, TumorCells, CulturedCell SurvivalDose-Response Relationship, DrugIndoleacetic AcidsLeydig CellsMaleMiceRatsRats, Inbred BNReceptors, GABASteroids4'-chlorodiazepam5-androsten-3,17,19-triolAndrostenolsBenzodiazepinonesBzrp protein, mouseIndoleacetic AcidsN,N-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamideReceptors, GABASteroids

Identifiers

PMID23525219
PMCPMC3740486
OpenAlexW2030315456

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.