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Testosterone is primarily produced in Leydig cells, where autophagy has been reported to be extremely active. However, the functional role of autophagy in testosterone synthesis remains unknown. In this study, we show that steroidogenic cell\u2013specific disruption of autophagy influenced the sexual behavior of aging male mice because of a reduction in serum testosterone, which is similar to the symptoms of LOH. The decline in testosterone was caused mainly by a defect in cholesterol uptake in autophagy-deficient Leydig cells. Further studies revealed that once autophagic flux was disrupted, Na+\/H+ exchanger regulatory factor 2 (NHERF2) accumulated in Leydig cells, resulting in the down-regulation of scavenger receptor class B, type I (SR-BI) and eventually leading to insufficient cholesterol supply. Collectively, these results reveal that autophagy promotes cholesterol uptake into Leydig cells by eliminating NHERF2, suggesting that dysfunction of autophagy might be causal in the loss of testosterone production in some patients.<\/jats:p>","DOI":"10.1083\/jcb.201710078","type":"journal-article","created":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T07:15:24Z","timestamp":1522826124000},"page":"2103-2119","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":208,"title":["Autophagy regulates testosterone synthesis by facilitating cholesterol uptake in Leydig cells"],"prefix":"10.1083","volume":"217","author":[{"given":"Fengyi","family":"Gao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China 1"},{"name":"School of Biotechnology and Food, Shangqiu Normal University, Shangqiu, China 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