Evidence map›Paper›PMID 21918126›Full record

ArticleBiology of reproduction2012

Simvastatin reduces steroidogenesis by inhibiting Cyp17a1 gene expression in rat ovarian theca-interstitial cells.

Israel Ortega, Amanda B Cress, Donna H Wong, Jesus A Villanueva, Anna Sokalska, Ben C Moeller, Scott D Stanley, Antoni J Duleba

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biology of reproduction, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
21.8field-weighted citation impact, top 1% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.

  1. The Effect of Statins on Levels of Dehydroepiandrosterone (DHEA) in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2019
    Pooled it
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  5. Obesity Affects IVF Outcomes and Mevalonic Acid Rescues the Side Effects of Statins on Follicle Growth.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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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

8 authors at 2 institutions in 3 countries.

Israel OrtegaDepartment of Obstetrics and Gynecology, School of Medicine, University of California-Davis, Sacramento, USA.
Amanda B Cress
Donna H Wong
Jesus A Villanueva
Anna Sokalska
Ben C Moeller
Scott D Stanley
Antoni J Duleba
University of California, Davis · USPoznan University of Medical Sciences · PL

Funding

Mevalonate pathway and thecal-interstitial functionR01HD050656 · NICHD · YALE UNIVERSITY · PI DULEBA, ANTONI J · 2007 to 2011
$1.6M
NICHD NIH HHS R01 HD050656NICHD NIH HHS R01-HD050656
6 · The paper itself

Abstract

Polycystic ovary syndrome (PCOS) is characterized by ovarian enlargement, theca-interstitial hyperplasia, and increased androgen production by theca cells. Previously, our group has demonstrated that statins (competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, a rate-limiting step of the mevalonate pathway) reduce proliferation of theca-interstitial cells in vitro and decrease serum androgen levels in women with PCOS. The present study evaluated the effect of simvastatin on rat ovarian theca-interstitial cell steroidogenesis. Because actions of statins may be due to reduced cholesterol availability and/or isoprenylation of proteins, the present study also investigated whether steroidogenesis was affected by cell- and mitochondrion-permeable 22-hydroxycholesterol, isoprenylation substrates (farnesyl-pyrophosphate [FPP] and geranylgeranyl-pyrophosphate [GGPP]), as well as selective inhibitors of farnesyltransferase (FTI) and geranylgeranyltransferase (GGTI). Theca-interstitial cells were cultured for 12, 24, and 48 h with or without simvastatin, GGPP, FPP, FTI, GGTI, and/or 22-hydroxycholesterol. Simvastatin decreased androgen levels in a time- and concentration-dependent fashion. This inhibitory effect correlated with a decrease in mRNA levels of Cyp17a1, the gene encoding the key enzyme regulating androgen biosynthesis. After 48 h, GGPP alone and FPP alone had no effect on Cyp17a1 mRNA expression; however, the inhibitory action of simvastatin was partly abrogated by both GGPP and FPP. The present findings indicate that statin-induced reduction of androgen levels is likely due, at least in part, to the inhibition of isoprenylation, resulting in decreased expression of CYP17A1.

Indexed as

Alkyl and Aryl TransferasesAnimalsCells, CulturedFarnesyltranstransferaseFemaleGene Expression Regulation, EnzymologicHydroxycholesterolsHydroxymethylglutaryl-CoA Reductase InhibitorsOvaryPolyisoprenyl PhosphatesRatsRats, Sprague-DawleyReal-Time Polymerase Chain ReactionRNA, MessengerSesquiterpenesSimvastatin22-hydroxycholesterolAlkyl and Aryl Transferasesfarnesyl pyrophosphateFarnesyltranstransferasegeranylgeranyl pyrophosphategeranylgeranyltransferase type-IHydroxycholesterolsHydroxymethylglutaryl-CoA Reductase InhibitorsPolyisoprenyl PhosphatesRNA, MessengerSesquiterpenesSimvastatinSteroid 17-alpha-Hydroxylase

Identifiers

PMID21918126
PMCPMC3313666
OpenAlexW2127075994

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.