Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

Wei Ren Li, Liang Chen, Zhi Jie Chang, Hua Xin, Tao Liu, Yan Quan Zhang, Guang Yong Li, Feng Zhou, Yan Qing Gong, Zhe Zhu Gao, Zhong Cheng Xin

Research output: Contribution to journalArticlepeer-review

53 Citations (SciVal)


Late-onset hypogonadism (LOH) is closely related to secondary androgen deficiency in aged males, but themechanism remains unclear. In this study, we found that reduced testosterone production in aged rat Leydig cells is associated with decreased autophagic activity. Primary rat Leydig cells and the TM3 mouse Leydig cell line were used to study the effect of autophagic deficiency on Leydig cell testosterone production. In Leydig cells from young and aged rats, treatment with wortmannin, an autophagy inhibitor, inhibited luteinising hormone (LH)-stimulated steroidogenic acute regulatory (StAR) protein expression and decreased testosterone production. In contrast, treatment with rapamycin, an autophagy activator, enhanced LH-stimulated steroidogenesis in Leydig cells from aged, but not young, rats. Intracellular reactive oxygen species (ROS) levels were increased in both young and aged Leydig cells treated with wortmannin but decreased only in aged Leydig cells treated with rapamycin. Furthermore, an increased level of ROS, induced by H 2O 2, resulted in LH-stimulated steroidogenic inhibition. Finally, knockdown of Beclin 1 decreased LH-stimulated StAR expression and testosterone production in TM3 mouse Leydig cells, which were associated with increased intracellular ROS level. These results suggested that autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells, which might be influenced by intracellular ROS levels.

Original languageEnglish
Pages (from-to)881-888
Number of pages8
JournalAsian Journal of Andrology
Issue number6
StatePublished - Nov 2011


  • Leydig cell
  • ageing
  • autophagy
  • late onset hypogonadism
  • reactive oxygen species
  • testosterone

ASJC Scopus subject areas

  • Urology


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