Evidence map›Paper›PMID 26446641›Full record

ArticleYonsei medical journal2015

The Role of Foxo3 in Leydig Cells.

Young Suk Choi, Joo Eun Song, Byung Soo Kong, Jae Won Hong, Silvia Novelli, Eun Jig Lee

Open access · goldAbstract read
In one paragraph

Article in Yonsei medical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.3field-weighted citation impact, top 39% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. The Liver-Testis Axis: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2026
    Review
  3. Transcriptomics Analysis of Testis Development inAnimals : an open access journal from MDPI · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. 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

6 authors at 3 institutions in 2 countries.

Young Suk ChoiEndocrinology, Institute of Endocrine Research, Brain Korea 21 PLUS Project for Medical Science and Yonsei University College of Medicine, Seoul, Korea.
Joo Eun SongEndocrinology, Institute of Endocrine Research, Brain Korea 21 PLUS Project for Medical Science and Yonsei University College of Medicine, Seoul, Korea.
Byung Soo KongEndocrinology, Institute of Endocrine Research, Brain Korea 21 PLUS Project for Medical Science and Yonsei University College of Medicine, Seoul, Korea.
Jae Won HongDepartment of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea.
Silvia NovelliEndocrinology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Eun Jig LeeEndocrinology, Institute of Endocrine Research, Brain Korea 21 PLUS Project for Medical Science and Yonsei University College of Medicine, Seoul, Korea. EJLEE423@yuhs.ac.
Yonsei University · KRInje University Ilsan Paik Hospital · KRNorthwestern University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeFoxo3 in female reproduction has been reported to regulate proliferation of granulose cells that form follicles. There are no reports so far that discuss on the role of Foxo3 in males. This study was designed to outline the role of Foxo3 in the testes. MATERIALS AND

methodsTestes from mice at birth to postpartum week (PPW) 5 were isolated and examined for the expression of Foxo3 using immunostaining. To elucidate role of Foxo3 in Leydig cells, R2C cells were treated with luteinizing hormone (LH) and the phosphorylation of Foxo3. Testosterone and steroidogenic acute regulatory (StAR) protein levels were measured after constitutive active [triple mutant (TM)] human FOXO3 adenovirus was transduced and StAR promoter assay was performed.

resultsFoxo3 expression in the testicles started from birth and lasted until PPW 3. After PPW 3, most Foxo3 expression occurred in the nuclei of Leydig cells; however, at PPW 5, Foxo3 was expressed in both the nucleus and cytoplasm. When R2C cells were treated with luteinizing hormone, Foxo3 phosphorylation levels by AKT increased. After blocking the PI3K pathway, LH-induced phosphorylated Foxo3 levels decreased, indicating that LH signaling regulates Foxo3 localization. When active FOXO3-TM adenovirus was introduced into a Leydig tumor cell line, the concentrations of testosterone and StAR protein decreased. When FOXO3 and a StAR promoter vector were co-transfected into HEK293 cells for a reporter assay, FOXO3 inhibited the StAR promoter.

conclusionFOXO3 affects testosterone synthesis by inhibiting the formation of StAR protein. LH hormone, meanwhile, influences Foxo3 localization, mediating its function.

Indexed as

AnimalsCell NucleusCellular SenescenceCytoplasmForkhead Box Protein O3Forkhead Transcription FactorsHEK293 CellsHumansLeydig CellsLuteinizing HormoneMaleMicePhosphatidylinositol 3-KinasesPhosphoproteinsPhosphorylationSignal TransductionForkhead Box Protein O3Forkhead Transcription FactorsFoxO3 protein, mouseLuteinizing HormonePhosphatidylinositol 3-KinasesPhosphoproteinsSteroidogenic Acute Regulatory ProteinTestosteroneFoxo3Leydig cellStARtestosterone

Identifiers

PMID26446641
PMCPMC4630047
OpenAlexW1946273149

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.