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The SET protein promotes androgen production in testicular Leydig cells
Author(s) -
Zhang B.,
Ma W.,
Zhu Q.,
Xu W.,
Gao L.,
Xu B.,
Xu S.,
Gao C.,
Gao L.,
Liu J.,
Cui Y.
Publication year - 2018
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12476
Subject(s) - cyp17a1 , androgen , gene knockdown , leydig cell , endocrinology , testosterone (patch) , medicine , biology , protein biosynthesis , transfection , human chorionic gonadotropin , cell culture , andrology , microbiology and biotechnology , hormone , luteinizing hormone , enzyme , biochemistry , genetics
Summary Approximately 40% of middle‐aged men exhibit symptoms of late‐onset hypogonadism ( LOH ). However, the mechanism of androgen deficiency is still currently unclear. As shown in our previous studies, the SET protein is expressed in testicular Leydig cells and ovarian granule cells. This study was designed to investigate the effect of the SET protein on androgen production in Leydig cells. The Ad CMV / SET and AdH1si RNA / SET adenoviruses were individually transduced into a cultured mouse Leydig cell line ( mLTC ‐1) with or without human chorionic gonadotropin ( HCG ) stimulation in vitro. The primary mouse Leydig cells were used to confirm the main data from mLTC ‐1 cells. The SET protein was expressed in the cytoplasm and nucleus of mLTC ‐1 cells. Testosterone production was significantly increased in mLTC ‐1 cells overexpressing the SET protein compared with the control group ( p < 0.05), whereas testosterone production was significantly decreased in the SET knockdown mLTC ‐1 cells ( p < 0.05). Consistent with the testosterone levels, the expression levels of the steroidogenic acute regulatory (St AR ) and cytochrome P450c17α‐hydroxylase ( CYP 17a1) mRNA s and proteins synchronously changed according to the expression level of the SET protein. Interestingly, the expression of the SET protein was significantly increased in the mLTC ‐1 cells stimulated with 0.04 and 0.1 U/mL hCG . In the mLTC ‐1 cells transfected with AdH1si RNA / SET and concurrently stimulated with 0.1 U/mL hCG , both testosterone production and St AR expression were significantly lower than in the cells without SET knockdown ( p < 0.05). In conclusion, the SET protein participates in regulating testosterone production by increasing the expression of St AR and CYP 17a1, and it may be a downstream factor of the classic luteinizing hormone ( LH )/luteinizing hormone receptor ( LHR ) signaling pathway. This study improves our understanding of the intracellular mechanism of testicular steroidogenesis and the pathophysiological mechanism of LOH in the aging male.