The SET protein promotes androgen production in testicular Leydig cells

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.

BMI1 promotes steroidogenesis through maintaining redox homeostasis in mouse MLTC-1 and primary Leydig cells

“…In the present study, MLTC-1 mouse Leydig cell line was used to study the role of BMI1 in steroidogenesis, due to stable and persistent production of testosterone by this type of cell [ 35 – 37 ]. By using small-molecule BMI1 specific inhibitor PTC-209 [ 38 , 39 ], we observed a drastic loss of BMI1 in MLTC-1 cells ( Figure 2(a ,b)).…”

Yangjing Capsule Increases Testosterone Production through SET/PI3K/Akt Pathway in Leydig Cell

“…An earlier study showed that SET protein was highly expressed in mouse Leydig cells [10]. A subsequent study showed that SET overexpression or knockdown could significantly promote or decrease testosterone production [11]. These results confirmed the relationship between SET and testosterone production in Leydig cells.…”

“…SET is reported to be a phosphorylated protein that is ubiquitously expressed in various tissues, particularly in steroidogenic cells within the adrenal gland and gonad, suggesting that it may be closely assiciated with steroidogenesis [19,20]. Previous work has shown that human chorionic gonadotropin (hCG) increased SET mRNA and protein expression through the cAMP/PKA signaling pathway to stimulate steroidogenic enzyme expression, which then promotes testosterone production in Leydig cells [11]. In the present study, we found that YC could paly a similar role to hCG in upregulating the expression of SET, StAR, P450scc, and HSD17B to stimulate steroidogenesis in Leydig cells both in vitro and in vivo.…”

Immunolocalization and expression of Siglec5 protein in the male reproductive tract of dromedary camel during rutting season

“…It is well known that Leydig cells stimulate spermatogenesis by secreting testosterone, a steroid hormone, which creates an environment that supports proper spermatogenesis development (Bing Chen et al, 2010; Sharpe et al, 1990). The synthesis and secretion of the testosterone is controlled by a network of intracellular and extracellular factors (Zhang et al, 2018). For example, a nuclear SE translocation (SET) protein is believed to promote steroidogenesis in Leydig cells (Dai et al, 2014; Zhang et al, 2018).…”

“…The synthesis and secretion of the testosterone is controlled by a network of intracellular and extracellular factors (Zhang et al, 2018). For example, a nuclear SE translocation (SET) protein is believed to promote steroidogenesis in Leydig cells (Dai et al, 2014; Zhang et al, 2018). Still, many details on the function and regulation of Leydig cells remain unknown (Zirkin & Papadopoulos, 2018).…”