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Liver X receptors interfere with the deleterious effect of diethylstilbestrol on testicular physiology.

Abstract：

:Liver X receptors LXRα (NR1H3) and LXRβ (NR1H2) are transcription factors belonging to the nuclear receptor superfamily, activated by specific oxysterols, oxidized derivatives of cholesterol. These receptors are involved in the regulation of testis physiology. Lxr-deficient mice pointed to the physiological roles of these nuclear receptors in steroid synthesis, lipid homeostasis and germ cell apoptosis and proliferation. Diethylstilbestrol (DES) is a synthetic estrogen considered as an endocrine disruptor that affects the functions of the testis. Various lines of evidences have made a clear link between estrogens, their nuclear receptors ERα (NR3A1) and ERβ (NR3A2), and Lxrα/β. As LXR activity could also be regulated by the nuclear receptor small heterodimer partner (SHP, NR0A2) and DES could act through SHP, we wondered whether LXR could be targeted by estrogen-like endocrine disruptors such as DES. For that purpose, wild-type and Lxr-deficient mice were daily treated with 0.75 μg DES from days 1 to 5 after birth. The effects of DES were investigated at 10 or 45 days of age. We demonstrated that DES induced a decrease of the body mass at 10 days only in the Lxr-deficient mice suggesting a protective effect of Lxr. We defined three categories of DES-target genes in testis: those whose accumulation is independent of Lxr; those whose accumulation is enhanced by the lack of both Lxrα/β; those whose accumulation is repressed by the absence of Lxrα/β. Lipid accumulation is also modified by neonatal DES injection. Lxr-deficient mice present different lipid profiles, demonstrating that DES could have its effects in part due to Lxrα/β. Altogether, our study shows that both nuclear receptors Lxrα and Lxrβ are not only basally important for testicular physiology but could also have a preventive effect against estrogen-like endocrine disruptors.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Oumeddour A,Viennois E,Caira F,Decourbey C,Maqdasy S,Tahraoui A,Baron S,Volle DH,Lobaccaro JM

doi

10.1016/j.bbrc.2013.12.005

subject

Has Abstract

pub_date

2014-04-11 00:00:00

pages

656-62

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(13)02061-5

journal_volume

446

pub_type

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Liver X receptors interfere with the deleterious effect of diethylstilbestrol on testicular physiology.