Protective Effect of Calretinin on Testicular Leydig Cells Via the Inhibition of Apoptosis

The core mechanism of Late-onset hypogonadism (LOH) is the deficiency of androgen due to the functional and quantitative decline of testicular Leydig cells. Here we explored the protective effect of calretinin, a Ca-binding protein, on Leydig cells. We found in MLTC-1 cells transfected with LV-calb2, the cell viability and optical density (OD) were higher (<0.05), cells in the S phase of the cell cycle were increased (<0.01) and p-ERK1/2 and p-AKT levels were significantly higher (<0.01 and <0.05), while in R2C cells transfected with LV-siRNA-calb2, all of the results mentioned above were adverse (<0.05). The cell apoptotic index after calretinin over-expressed was significantly lower (<0.001), while the expression levels of mitochondria-related apoptotic factors such as cleaved caspase-9 and cytochrome C (cyto C) were lower and ratio of Bcl2/Bax was higher (0.05). After calretinin down-regulated, the apoptotic index was higher (0.05), while the expression levels of mitochondria-related apoptotic factors were higher and the ratio of Bcl2/Bax was lower (0.05). Therefore, calretinin increases Leydig cell viability and proliferation, possibly via ERK1/2 and AKT pathways, and suppresses apoptosis possibly via the mitochondria-related apoptotic pathway, which could be beneficial in understanding the pathophysiology of LOH and could lead to the study of new treatments.