Evidence map›Paper›PMID 31599939›Full record

ArticleEndocrinology2019

Inflammatory Stimuli Trigger Increased Androgen Production and Shifts in Gene Expression in Theca-Interstitial Cells.

Chelsea W Fox, Lingzhi Zhang, Abhishek Sohni, Manuel Doblado, Miles F Wilkinson, R Jeffrey Chang, Antoni J Duleba

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 4% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
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  13. On the Intimate Relationship of Adiposity to Polycystic Ovary Syndrome.The Journal of clinical endocrinology and metabolism · 2025
    Review
  14. Article
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  18. Review
  19. Pro-inflammatory cytokines disruptFrontiers in endocrinology · 2025
    Article
  20. 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.

Chelsea W FoxDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, School of Medicine, La Jolla, California.
Lingzhi ZhangDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, School of Medicine, La Jolla, California.
Abhishek SohniDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, School of Medicine, La Jolla, California.
Manuel DobladoDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, School of Medicine, La Jolla, California.
Miles F WilkinsonDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, School of Medicine, La Jolla, California.
R Jeffrey ChangDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, School of Medicine, La Jolla, California.
Antoni J DulebaDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, School of Medicine, La Jolla, California.
University of California San Diego · US

Funding

The Interaction of Neuroendocrine Repro. Function and Metabolic SignalingU54HD012303 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MELLON, PAMELA L · 1999 to 2013
$18.0M
The Role of FSH in Female InfertilityP50HD012303 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LAWSON, MARK ANDREW · 1985 to 2020
$7.5M
TRAINING IN REPRODUCTIVE SCIENCEST32HD007203 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PAMELA L MELLON · 1988 to 2026
$4.8M
NICHD NIH HHS P50 HD012303NICHD NIH HHS T32 HD007203NICHD NIH HHS U54 HD012303
6 · The paper itself

Abstract

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by theca cell hyperplasia and excessive androgen production. An increasing body of evidence has pointed to a close association between PCOS and low-grade chronic systemic inflammation. However, the mechanistic basis for this linkage is unknown. Therefore, we evaluated the effects of the inflammatory agents lipopolysaccharide (LPS) and IL-1β on rat theca-interstitial cells (TICs). We found that incubation with either LPS or IL-1β elicited a dose-dependent increase in both TIC viability and androgen production. Using RNA sequencing analysis, we found that both of these inflammatory agents also triggered profound and widespread shifts in gene expression. Using a stringent statistical cutoff, LPS and IL-1β elicited differential expression of 5201 and 5953 genes, respectively. Among the genes upregulated by both LPS and IL-1β were key regulatory genes involved in the cholesterol and androgen biosynthesis pathways, including Cyp17a1, Cyp11a1, Hsd3b, and Hmgcr. This provides a molecular explanation for the mechanism of action of inflammatory agents leading to increased androgen production. Gene ontology and pathway analysis revealed that both LPS and IL-1β regulated genes highly enriched for many common functions, including the immune response and apoptosis. However, a large number of genes (n = 2222) were also uniquely regulated by LPS and IL-1β, indicating that these inflammatory mediators have substantial differences in their mechanism of action. Together, these findings highlight the potential molecular mechanisms through which chronic low-grade inflammation contributes to the pathogenesis of androgen excess in PCOS.

Indexed as

AndrogensAnimalsFemaleGene ExpressionInflammationInterleukin-1betaLipopolysaccharidesMevalonic AcidPolycystic Ovary SyndromeRats, Sprague-DawleyTheca CellsAndrogensInterleukin-1betaLipopolysaccharidesMevalonic Acid

Identifiers

PMID31599939
PMCPMC6855291
OpenAlexW2979852387

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.