The Improvement of Exercise Training on Diabetes‐Damaged cAMP and Steroidogenesis Pathway in Leydig Cells of Streptozotocin‐Induced Diabetes Rat
Authors: Lin Ting Wen , Tsai Shiow‐Chwen , Lu Chien‐Chen , Chen Chiao‐Nan , Chen Chih‐Chieh 
Published: November 2023

IntroductionDiabetes mellitus not only significantly impact metabolism and healthy status, but also limits testicular function and cause lower serum testosterone in male. Acute swimming stimulated gonadotropin‐stimualted testosterone secretion.Purposeto investigate the mechanism of lower production of testosterone in Leydig cells of streptozotocin (STZ)‐induced diabetes mellitus (DM) rats. The mechanism of endurance exercise training on production of testosterone was also analyzed.Materials and MethodsThirty two Sprague‐Dawley male rats were divided into four groups, including control, endurance exercise training (EX), STZ‐induced diabetes (DM), diabetes combined with training (DM+EX). The rats in DM group were intraperitoneally injected with STZ (50 mg/kg body weight in 0.1 M citrate buffer, pH 4.5) to induce diabetes. Control rats just injected buffer. After the rats presented DM, EX and DM+EX started to train on treadmill. After four weeks, all the rats were sacrificed and Leydig cells of testis were collected. The Leydig cells were cultured with some ligands for 1 hour to test the steroidogenesis pathway. The culture medium were collected to measure testosterone by using radioimmunoassay. The ligands included human chorionic gonadotropin (hCG, 0.05 IU/ml, to mimic stimulation of luteinizing hormone), forskolin (10−5 M, stimulator of adenylyl cyclase), 8‐bromo‐cAMP (0.1 mM, to increase the intracellular cAMP), 25‐hydroxycholesterol (10−5 M, 25‐OHC) and androstenedione (10−6 M, ANDR) were added in culture medium. All data were presented as mean ± standard error mean and compare the differences by one way analysis of variances. The alpha level was set at 0.05 (p<0.05) for statistical difference.ResultThe testosterone production of Leydig cells was significantly decreased in diabetes (p<0.01) and exercise training group (p<0.05) than that of control group. Administration of, forskolin, 8‐bromo‐cAMP, and precursors of steroidogenesis (25‐OHC and ANDR) significantly stimulated testosterone production (p<0.01). Compared with control group, both of diabetes and exercise significant lower basal and hCG‐stimulated production of testosterone (p<0.05). Combination of diabetes and exercise did not show adverse inhibitory effect. Compared the response fold of hCG‐stimulated testosterone production, there were no difference among the four groups. Administration of forskolin totally reversed testosterone production in DM and EX groups. While add with 8‐Br‐cAMP, only DM group resulted a significant decreased testosterone production than control group. Administration of 25‐OHC, bypass StAR‐mediated translocation on the mitochondria membrane of Leydig cells, stimulated testosterone production and abolished the inhibitory effect of diabetes and exercise. ANDR, works as precursor to enhance synthesis of testosterone, presented similar result of 25‐OHC.ConclusionOur results concluded that exercise could improve the diabetes‐damage post‐cAMP activation pathway.Support or Funding InformationMOST l102‐2410‐H‐845‐014‐MY3