Abstract
SummaryApproximately 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 AdCMV/SET and AdH1siRNA/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 (StAR) and cytochrome P450c17α‐hydroxylase (CYP17a1) mRNAs 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 AdH1siRNA/SET and concurrently stimulated with 0.1 U/mL hCG, both testosterone production and StAR 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 StAR and CYP17a1, 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.
Highlights
40% of middle-aged men exhibit symptoms of late-onset hypogonadism (LOH), known as partial androgen deficiency in the aging male (PADAM) (Lunenfeld et al, 2005)
The rabbit polyclonal anti-SET antibody was obtained from Santa Cruz Biotechnology Inc. (Santa Cruz, CA, USA), the rabbit monoclonal anti-glyceraldehyde 3-phosphate dehydrogenase (GAPDH) antibody was obtained from ABCAM (Cambridge Science Park, Cambridge, UK), the rabbit monoclonal anti- CYP17a1 antibody was obtained from ABGENT (San Diego, CA, USA), and the rabbit monoclonal anti-steroidogenic acute regulatory (StAR) antibody was obtained from Cell Signaling Technology (Denver, CO, USA)
We found that the SET protein was a potential downstream factor of luteinizing hormone (LH)/luteinizing hormone receptor (LHR) signaling with a stimulatory effect on T production in Leydig cells by upregulating the expressions of key factors and enzymes involved in steroidogenesis, such as StAR, CYP17a1, CYP11a1, and HSD3b1
Summary
40% of middle-aged men exhibit symptoms of late-onset hypogonadism (LOH), known as partial androgen deficiency in the aging male (PADAM) (Lunenfeld et al, 2005). LOH has even been shown to be related to substantially higher risks of all-cause and cardiovascular mortality in aging males (Pye et al, 2014). The core mechanism of LOH is an absolute or relative androgen deficiency due to decreases in the number and function of testicular Leydig cells (Lunenfeld et al, 2005). The mechanism and pathophysiology of LOH are complicated and not completely understood at present. The main functions of the testis are spermatogenesis and androgen production.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
