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Triphenyltin chloride reduces the development of rat adrenal cortex during puberty
Xingwang Li1, Linchao Li1, Xiuxiu Chen1
1Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People's Republic of China.
Abstract:
Triphenyltin has been classified as an endocrine disruptor. However, whether triphenyltin interferes with the adrenal glands during puberty remains unknown. Here, we reported the effects of triphenyltin on the adrenal glands in rats. Male Sprague Dawley rats (age of 35 days) were orally administered with 0, 0.5, 1, or 2 mg/kg/day triphenyltin for 18 days. Triphenyltin significantly lowered corticosterone levels at 1 and 2 mg/kg and adrenocorticotropic hormone at 2 mg/kg. The RNA-Seq analysis detected multiple differentially expressed genes. Four down-regulated genes were transcription factor genes (Nr4a1, Nr4a2, Nr4a3, and Ppard), which might be associated with the suppression of the adrenal cortex function. RNA-seq and qPCR showed that triphenyltin dose-dependently down-regulated the expression of the genes for cholesterol transport and biosynthesis, including Scarb1, Ldlr, Hmgcs1, Hmgcr, and Hsd17b7. Further Western blotting revealed that it lowered NR4A1, PPRAD, LDLR, and HMGCS1 protein levels. We treated H295R adrenal cells with 1-100 nM triphenyltin for 72 h. Triphenyltin induced significant higher ROS production at 100 nM and did not induce apoptosis at 10 and 100 nM. In conclusion, triphenyltin inhibits production of corticosterone via blocking the expression of cholesterol uptake transporters and cholesterol biosynthesis.
Insights
Triphenyltin exposure in male rats during puberty significantly reduced corticosterone and adrenocorticotropic hormone levels. This endocrine disruptor inhibits adrenal function by blocking cholesterol transport and biosynthesis pathways.
Area of Science:
- Endocrinology
- Toxicology
- Molecular Biology
Background:
- Triphenyltin is a known endocrine disruptor.
- Its effects on adrenal glands during puberty are not well understood.
Purpose of the Study:
- To investigate the impact of triphenyltin on adrenal gland function in male rats during puberty.
- To elucidate the molecular mechanisms underlying triphenyltin's effects on corticosterone production.
Main Methods:
- Male Sprague Dawley rats were administered varying doses of triphenyltin.
- RNA-sequencing (RNA-Seq), quantitative polymerase chain reaction (qPCR), and Western blotting were employed.
- H295R adrenal cells were used for in vitro studies.
Main Results:
- Triphenyltin significantly decreased corticosterone and adrenocorticotropic hormone levels.
- Down-regulation of key genes involved in cholesterol transport (Scarb1, Ldlr) and biosynthesis (Hmgcs1, Hmgcr, Hsd17b7) was observed.
- Triphenyltin increased reactive oxygen species (ROS) production in adrenal cells without inducing apoptosis.
Conclusions:
- Triphenyltin inhibits corticosterone production by suppressing adrenal cortex function.
- This inhibition is mediated by blocking the expression of genes for cholesterol uptake and biosynthesis.
- Triphenyltin acts as an endocrine disruptor affecting adrenal steroidogenesis.
