2. Academic Validation
  3. Acephate interferes with androgen synthesis in rat immature Leydig cells

Acephate interferes with androgen synthesis in rat immature Leydig cells

  • Chemosphere. 2020 Apr;245:125597. doi: 10.1016/j.chemosphere.2019.125597.
Yiyan Wang 1,  Yaoyao Dong 2,  Siwen Wu 1,  Qiqi Zhu 1,  Xiaoheng Li 1,  Shiwen Liu 1,  Tongliang Huang 1,  Huitao Li 1,  Ren-Shan Ge 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325003, China.
  • 2 Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325003, China.
  • 3 Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325003, China. Electronic address: [email protected].
PMID: 31864041 DOI: 10.1016/j.chemosphere.2019.125597
Abstract

Acephate is an organophosphate pesticide. It is widely used. However, whether it inhibits androgen synthesis and metabolism remains unclear. In the current study, we investigated the effect of acephate on the inhibition of androgen synthetic and metabolic pathways in rat immature Leydig cells after 3-h culture. Acephate inhibited basal androgen output in a dose-dependent manner with the inhibition starting at 0.5 μM. It significantly inhibited luteinizing hormone and 8-Br-cAMP stimulated androgen output at 50 μM. It significantly inhibited progesterone-mediated androgen output at 50 μM. Further study demonstrated that acephate down-regulated the expression of Hsd3b1 and its protein at ≥ 0.5 μM, Lhcgr at 5 μM and Star at 50 μM. Acephate directly blocked rat testicular HSD3B1 activity at 50 μM. Acephate did not affect other androgen synthetic and metabolic Enzyme activities as well as ROS production, proliferation, and Apoptosis of immature Leydig cells. In conclusion, acephate targets LHCGR, STAR, and HSD3B1, thus blocking androgen synthesis in rat immature Leydig cells and HSD3B1 is being the most sensitive target of acephate.

Keywords

3β-hydroxysteroid dehydrogenase isoform 1; Acephate; Luteinizing hormone receptor; Rat immature Leydig cells; Steroidogenesis; Steroidogenic enzymes.

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