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Volume 13, Issue 6 (November 2011) 13, 881–888; 10.1038/aja.2011.85

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

Wei-Ren Li1,*, Liang Chen2,*, Zhi-Jie Chang3, Hua Xin1, Tao Liu1, Yan-Quan Zhang3, Guang-Yong Li1, Feng Zhou1, Yan-Qing Gong1, Zhe-Zhu Gao1 and Zhong-Cheng Xin1

1 Andrology Center, Peking University First Hospital, Peking University, Beijing 100034, China
2 Department of Urology, China Meitan General Hospital, Beijing 100028, China
3 Department of Biological Sciences and Biotechnology, School of Medicine, Tsinghua University, Beijing 100084, China

* These authors contributed equally to this study.

Correspondence: Dr ZC Xin, (xinzc@bjmu.edu.cn)

Received 15 March 2011; Revised 28 April 2011; Accepted 16 May 2011; Published online 8 August 2011


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 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(2)O(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.

Keywords: ageing; autophagy; late onset hypogonadism; Leydig cell; reactive oxygen species; testosterone

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