Evidence map›Paper›PMID 34171102›Full record

ArticleEndocrinology2021

The FOS/AP-1 Regulates Metabolic Changes and Cholesterol Synthesis in Human Periovulatory Granulosa Cells.

Yohan Choi, Hayce Jeon, James W Akin, Thomas E Curry, Misung Jo

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2021. 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
6.5field-weighted citation impact, top 3% 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, 46 citations in OpenAlex.

  1. Trial
  2. Single-cell atlas of the mouse ovary reveals molecular drivers of aging and senescence during the estropausal transition.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  19. Granulosa cell expression of Fos is critical for regulating ovulatory gene expressions in the mouse ovary.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
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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

5 authors at 2 institutions in 1 country.

Yohan ChoiDepartment of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Hayce JeonDepartment of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
James W AkinBluegrass Fertility Center, KY 40509, USA.
Thomas E CurryDepartment of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
Misung JoDepartment of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.ORCID 0000-0001-6894-3388
University of Kentucky · USBluegrass Care Navigators · US

Funding

University of Kentucky Markey Cancer Center Support Grant ECIA SupplementP30CA177558 · NCI · UNIVERSITY OF KENTUCKY · PI Bernard Mark Evers · 2013 to 2026
$38.3M
Ovulation and Luteal Formation in Rodents Monkeys and WomenP01HD071875 · NICHD · UNIVERSITY OF KENTUCKY · PI CURRY, THOMAS E · 2014 to 2018
$6.1M
The Role of FOS in the OvaryR01HD096077 · NICHD · UNIVERSITY OF KENTUCKY · PI JO, MISUNG · 2019 to 2024
$2.0M
The Function of Progesterone Receptor in Human Ovulatory FolliclesR03HD095098 · NICHD · UNIVERSITY OF KENTUCKY · PI JO, MISUNG · 2018 to 2019
$153k
NCI NIH HHS P30 CA177558NICHD NIH HHS P01 HD071875NICHD NIH HHS R01 HD096077NICHD NIH HHS R03 HD095098
6 · The paper itself

Abstract

FOS, a subunit of the activator protein-1 (AP-1) transcription factor, has been implicated in various cellular changes. In the human ovary, the expression of FOS and its heterodimeric binding partners JUN, JUNB, and JUND increases in periovulatory follicles. However, the specific role of the FOS/AP-1 remains elusive. The present study determined the regulatory mechanisms driving the expression of FOS and its partners and functions of FOS using primary human granulosa/lutein cells (hGLCs). Human chorionic gonadotropin (hCG) induced a biphasic increase in the expression of FOS, peaking at 1 to 3 hours and 12 hours. The levels of JUN proteins were also increased by hCG, with varying expression patterns. Coimmunoprecipitation analyses revealed that FOS is present as heterodimers with all JUN proteins. hCG immediately activated protein kinase A and p42/44MAPK signaling pathways, and inhibitors for these pathways abolished hCG-induced increases in the levels of FOS, JUN, and JUNB. To identify the genes regulated by FOS, high-throughput RNA sequencing was performed using hGLC treated with hCG ± T-5224 (FOS inhibitor). Sequencing data analysis revealed that FOS inhibition affects the expression of numerous genes, including a cluster of genes involved in the periovulatory process such as matrix remodeling, prostaglandin synthesis, glycolysis, and cholesterol biosynthesis. Quantitative PCR analysis verified hCG-induced, T-5224-regulated expression of a selection of genes involved in these processes. Consistently, hCG-induced increases in metabolic activities and cholesterol levels were suppressed by T-5224. This study unveiled potential downstream target genes of and a role for the FOS/AP-1 complex in metabolic changes and cholesterol biosynthesis in granulosa/lutein cells of human periovulatory follicles.

Indexed as

Cells, CulturedCholesterolChorionic GonadotropinEnergy MetabolismFemaleGene Expression RegulationGranulosa CellsHumansOvulationProto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junTime FactorsTranscription Factor AP-1CholesterolChorionic GonadotropinFOS protein, humanProto-Oncogene Proteins c-fosProto-Oncogene Proteins c-junTranscription Factor AP-1FOSgranulosa cellshumanJUN proteinsovulation

Identifiers

PMID34171102
PMCPMC8315293
OpenAlexW3176951117

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.