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Flurbiprofen Inhibits Androgen Productions in Rat Immature Leydig Cells

Yiyan Wang1, Wenwen Zheng1, Yuanyuan Shan2

  • 1Department of Anesthesiology , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , Zhejiang 325027 , People's Republic of China.

Chemical Research in Toxicology
|June 12, 2019
PubMed

Insights

Flurbiprofen, a nonsteroidal anti-inflammatory drug, inhibits androgen production in rat Leydig cells by directly reducing 3β-hydroxysteroid dehydrogenase activity and gene expression. This leads to decreased androgen secretion and increased cell apoptosis.

Area of Science:

  • Endocrinology
  • Reproductive Biology
  • Pharmacology

Background:

  • Leydig cells are crucial for testicular androgen biosynthesis.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) effects on Leydig cell function are not fully understood.
  • Flurbiprofen is a commonly used NSAID.

Purpose of the Study:

  • To investigate the effects of flurbiprofen on androgen biosynthesis in immature rat Leydig cells.
  • To determine the specific mechanisms by which flurbiprofen may impact Leydig cell function.

Main Methods:

  • Immature rat Leydig cells were cultured with varying concentrations of flurbiprofen.
  • Androgen levels, gene expression (HSD3B, Srd5a1, Akr1c14, Lhcgr), reactive oxygen species (ROS) generation, and apoptosis were measured.
  • Direct enzyme activity assays for HSD3B were performed.

Main Results:

  • Flurbiprofen significantly inhibited basal and stimulated androgen production.
  • Flurbiprofen competitively inhibited rat and human HSD3B activity.
  • Flurbiprofen down-regulated the expression of Srd5a1, Akr1c14, and Lhcgr.
  • Flurbiprofen increased ROS production and Leydig cell apoptosis.

Conclusions:

  • Flurbiprofen directly inhibits HSD3B activity and key gene expression in Leydig cells.
  • Flurbiprofen reduces androgen secretion and induces oxidative stress and apoptosis in Leydig cells.
  • These findings suggest potential adverse effects of flurbiprofen on male reproductive function.

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