Evidence map›Paper›PMID 23022511›Full record

ArticleToxicology and applied pharmacology2012

Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4.

Marek Kucka, Kristina Pogrmic-Majkic, Svetlana Fa, Stanko S Stojilkovic, Radmila Kovacevic

Abstract read
In one paragraph

Article in Toxicology and applied pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.

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  13. Profiling the endocrine-disrupting properties of triazines, triazoles, and short-chain PFAS.Toxicological sciences : an official journal of the Society of Toxicology · 2024
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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 2 countries.

Marek KuckaSection on Cellular Signaling, Program in Developmental Neuroscience, NICHD, NIH, Bethesda, MD, USA.
Kristina Pogrmic-Majkic
Svetlana Fa
Stanko S Stojilkovic
Radmila Kovacevic
University of Novi Sad · RSEunice Kennedy Shriver National Institute of Child Health and Human Development · US

Funding

Intracellular Signaling In Endocrine CellsZIAHD000195 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI STOJILKOVIC, STANKO S. · 2009 to 2025
$18.8M
INTRACELLULAR SIGNALING IN ENDOCRINE CELLSZ01HD000195 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI STOJILKOVIC, STANKO S. · 1994 to 2008
$2.4M
Intramural NIH HHS Z01 HD000195
6 · The paper itself

Abstract

Atrazine, one of the most commonly used herbicides worldwide, acts as an endocrine disruptor, but the mechanism of its action has not been characterized. In this study, we show that atrazine rapidly increases cAMP levels in cultured rat pituitary and testicular Leydig cells in a concentration-dependent manner, but less effectively than 3-isobutyl-1-methylxanthine, a competitive non-specific inhibitor of phosphodiesterases (PDEs). In forskolin (an activator of adenylyl cyclase)- and probenecid (an inhibitor of cyclic nucleotide transporters)-treated cells, but not in 3-isobutyl-1-methylxanthine-treated cells, atrazine further increased cAMP levels, indicating that inhibition of PDEs accounts for accumulation of cAMP. In contrast to cAMP, atrazine did not alter cGMP levels, further indicating that it inhibits cAMP-specific PDEs. Atrazine-induced changes in cAMP levels were sufficient to stimulate prolactin release in pituitary cells and androgen production in Leydig cells, indicating that it acts as an endocrine disrupter both in cells that secrete by exocytosis of prestored hormones and in cells that secrete by de novo hormone synthesis. Rolipram abolished the stimulatory effect of atrazine on cAMP release in both cell types, suggesting that it acts as an inhibitor of PDE4s, isoforms whose mRNA transcripts dominate in pituitary and Leydig cells together with mRNA for PDE8A. In contrast, immortalized lacto-somatotrophs showed low expression of these mRNA transcripts and several fold higher cAMP levels compared to normal pituitary cells, and atrazine was unable to further increase cAMP levels. These results indicate that atrazine acts as a general endocrine disrupter by inhibiting cAMP-specific PDE4s.

Indexed as

Endocrine Disruptors3',5'-Cyclic-AMP PhosphodiesterasesAdenylyl CyclasesAndrogensAnimalsAtrazineCells, CulturedChorionic GonadotropinCyclic AMPExocytosisHerbicidesLeydig CellsMalePituitary Gland, AnteriorPolymerase Chain ReactionProlactin3',5'-Cyclic-AMP PhosphodiesterasesAdenylyl CyclasesAndrogensAtrazineChorionic GonadotropinCyclic AMPEndocrine DisruptorsHerbicidesPde4a protein, ratProlactinRNA, MessengerRolipram

Identifiers

PMID23022511
PMCPMC4181665
OpenAlexW2087799143

What OpenQuestion holds

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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.