MR 10. Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells
Male Reproduction

MR 10. Autophagic deficiency is related to steroidogenic decline in aged rat Leydig cells

Wei-Ren Li1, Lei Hou1, Zhi-Jie Chang2, Hua Xin3, Tao Liu3, Guang-Yong Li3, Feng Zhou3, Yan-Qing Gong3, Zhe-Zhu Gao3, Zhong-Cheng Xin3

1Beijing General Aerospace Hospital, Beijing 100076, China; 2Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China; 3Andrology Center, Peking University First Hospital, Peking University, Beijing 100034, China

Late-onset hypogonadism (LOH) is closely related to secondary androgen deficiency in aged males, but the mechanism 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 LHstimulated 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 H2O2, 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. In conclusion, autophagic deficiency plays an important role in the decreased testosterone production of aged Leydig cells and increased intracellular ROS may be involved in this process.

Key words

Ageing; autophagy; late onset hypogonadism; leydig cell; reactive oxygen species; testosterone

DOI: 10.3978/j.issn.2223-4683.2012.s103

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