Katsuji Aizawa

Testosterone and DHEA activate the glucose metabolism-related signaling pathway in skeletal muscle

Circulating dehydroepiandrosterone (DHEA) is converted to testosterone or estrogen in the target tissues. Recently, we demonstrated that skeletal muscles are capable of locally synthesizing circulating DHEA to testosterone and estrogen. Furthermore, testosterone is converted to 5alpha-dihydrotestosterone (DHT) by 5alpha-reductase and exerts biophysiological actions through binding to androgen receptors. However, it remains unclear whether skeletal muscle can synthesize DHT from testosterone and/or DHEA and whether these hormones affect glucose metabolism-related signaling pathway in skeletal muscles. We hypothesized that locally synthesized DHT from testosterone and/or DHEA activates glucose transporter-4 (GLUT-4)-regulating pathway in skeletal muscles. The aim of the present study was to clarify whether DHT is synthesized from testosterone and/or DHEA in cultured skeletal muscle cells and whether these hormones affect the GLUT-4-related signaling pathway in skeletal muscles. In the present study, the expression of 5alpha-reductase mRNA was detected in rat cultured skeletal muscle cells, and the addition of testosterone or DHEA increased intramuscular DHT concentrations. Addition of testosterone or DHEA increased GLUT-4 protein expression and its translocation. Furthermore, Akt and protein kinase C-zeta/lambda (PKC-zeta/lambda) phosphorylations, which are critical in GLUT-4-regulated signaling pathways, were enhanced by testosterone or DHEA addition. Testosterone- and DHEA-induced increases in both GLUT-4 expression and Akt and PKC-zeta/lambda phosphorylations were blocked by a DHT inhibitor. Finally, the activities of phosphofructokinase and hexokinase, main glycolytic enzymes, were enhanced by testosterone or DHEA addition. These findings suggest that skeletal muscle is capable of synthesizing DHT from testosterone, and that DHT activates the glucose metabolism-related signaling pathway in skeletal muscle cells.

Acupuncture and responses of immunologic and endocrine markers during competition

INTRODUCTION Acupuncture is used to modulate the physical well-being of athletes in Asian countries. However, there is little information on the immediate effects of acupuncture treatment on physiological or psychological responses to exercise. PURPOSE The purpose of this study was to examine the effect of acupuncture treatment on the physical well-being of elite female soccer players during a competition period. METHODS Subjects were divided into two groups: those who received acupuncture treatment (18.1 +/- 2.3 yr [+/-SD], N = 9) and a control group (17.7 +/- 2.8 yr, N = 12). In the treatment group, acupuncture stimulus was applied at LI 4 (Goukoku), ST 36 (Ashi-sanri) for 20 min, and ST 6 (Kyosya), LU 6 (Ko-sai) points for 15 min 4 h after the game every night during the competition period. The measured parameters included salivary secretory immunoglobulin A (SIgA) level, cortisol level in saliva, subjective rating of physical well-being, and profile of mood states (POMS). RESULTS The following were the main results: 1). Exercise-induced decrease of salivary SIgA and increase of salivary cortisol were inhibited by acupuncture. 2). Acupuncture improved subjective rating of muscle tension and fatigue. 3). The POMS score was modulated by acupuncture. CONCLUSION These results support the effectiveness of acupuncture for physical and mental well-being of athletes.

Acute exercise activates local bioactive androgen metabolism in skeletal muscle.

Androgens, such as testosterone, play important roles in regulation of diverse physiological process of target tissues. Recently, we reported that steroidogenic enzymes exist in skeletal muscle and regulate local production of testosterone in response to exercise. Testosterone is transformed into a bioactive androgen metabolite, dihydrotestosterone (DHT) by 5alpha-reductase. However, it is unclear whether exercise stimulates local bioactive androgen metabolism in the skeletal muscle in both sexes. In the present study, we examined sex differences in the levels of dehydroepiandrosterone (DHEA), free testosterone, DHT, and steroidogenesis-related enzymes 5alpha-reductase and androgen receptor (AR) in rats skeletal muscle before and after a single bout of exercise. Basal muscular free testosterone and DHT levels were higher in males than females, whereas the levels of DHEA did not differ between the sexes. Muscular DHEA, free testosterone, and DHT levels were increased in both sexes after the exercise. There were no differences of 5alpha-reductase and AR transcripts and proteins between the sexes, and the expression of 5alpha-reductase was significantly increased in both sexes after the exercise. Finally, the expression of AR was significantly higher in female rats, but not in males after the exercise. These data suggest that acute exercise enhances the local bioactive androgen metabolism in the skeletal muscle of both sexes.

DHEA improves impaired activation of Akt and PKC ζ/λ-GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin-induced diabetes rats

Aim:  Addition of dehydroepiandrosterone (DHEA) to a cultured skeletal muscle locally synthesizes 5α‐dihydrotestosterone (DHT). It induced activation of glucose metabolism‐related signalling pathway via protein kinase B (Akt) and protein kinase C zeta/lambda (PKC ζ/λ)‐glucose transporter‐4 (GLUT4) proteins. However, such an effect of DHEA in vivo remains unclear.

A rat model of saliva secretory immunoglobulin: a suppression caused by intense exercise

We aimed to develop a valid model of immunosuppression induced by intense exercise in rats. Rats were divided into three groups. In the rest (Rest) group, saliva was collected from resting rats on 4 consecutive days. In the exercise (Ex) group, rats ran on a treadmill untill exhaustion (exercise time: 60.0 ± 3.7 min), and their saliva was collected before and after exercise; the salivary glands were removed after exercise. In the control (Con) group, saliva collection and gland removal were also performed, but the rats did not exercise. Secretory immunoglobulin A (SIgA) concentrations in saliva and polymeric immunoglobulin receptor (pIgR) mRNA expression in the glands were measured. There was no significant change in SIgA concentration in the Rest group over 4 days. In the Ex group, SIgA concentration decreased significantly after exercise compared with before, whereas there was no significant change in the Con group. The expression of pIgR mRNA was significantly lower in the Ex group post‐exercise than in the Con group. Our procedure for saliva collection appeared suitable, and the exercise‐induced SIgA suppression was probably caused by a decline in pIgR mRNA expression. We propose to use this reproducible and reliable rat model of exercise‐induced SIgA suppression in future studies.

DHEA administration and exercise training improves insulin resistance in obese rats

BackgroundDehydroepiandrosterone (DHEA) is precursor of sex steroid hormone. We demonstrated that acute DHEA injection to type 1 diabetes model rats induced improvement of hyperglycemia. However, the effect of the combination of DHEA administration and exercise training on insulin resistance is still unclear. This study was undertaken to determine whether 6-weeks of DHEA administration and/or exercise training improve insulin resistance in obese male rats.MethodsAfter 14 weeks of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of four groups: control, DHEA administration, exercise training, and a combination of DHEA administration and exercise training (n = 10 each group).ResultsAfter 6-weeks of DHEA administration and/or exercise training, rats in the combination group weighed significantly less and had lower serum insulin levels than rats in the other groups. Moreover, the rats treated with DHEA alone or DHEA and exercise had significantly lower fasting glucose levels (combination, 84 ± 6.5 mg/dL; DHEA, 102 ± 9.5 mg/dL; control, 148 ± 10.5 mg/dL). In addition, insulin sensitivity check index showed significant improvements in the combination group (combination, 0.347 ± 0.11; exercise, 0.337 ± 0.16%; DHEA, 0.331 ± 0.14; control, 0.308 ± 0.12). Muscular DHEA and 5α-dihydrotestosterone (DHT) concentrations were significantly higher in the combination group, and closely correlated with the quantitative insulin-sensitivity check index (DHEA: r = 0.71, p < 0.01; DHT: r = 0.69, p < 0.01).ConclusionThese results showed that a combination of DHEA administration and exercise training effectively improved fasting blood glucose and insulin levels, and insulin sensitivity, which may reflect increased muscular DHEA and DHT concentrations.

Increased muscular dehydroepiandrosterone levels are associated with improved hyperglycemia in obese rats

This study was undertaken to assess the effects of dehydroepiandrosterone (DHEA) administration and exercise training on muscular DHEA and 5α-dihydrotestosterone (DHT) levels and hyperglycemia in diet-induced obese and hyperglycemic rats. After 14 wk of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of three 6-wk regimens: control, DHEA treatment, or exercise training (running at 25 m/min for 1 h, 5 days/wk; n = 10 each group). Results indicate that either 6 wk of DHEA treatment or exercise training significantly attenuated serum insulin and fasting glucose levels compared with the control group. Plasma and muscle concentrations of DHEA and DHT and expression levels of 5α-reductase were significantly higher in the DHEA-treated and exercise-training groups. Moreover, both DHEA administration and exercise training upregulated GLUT4 translocation with concomitant increases in protein kinase B and protein kinase Cζ/λ phosphorylation. Muscle DHEA and DHT concentrations closely correlated with blood glucose levels (DHEA treatment: r = -0.68, P < 0.001; exercise training: r = -0.65, P < 0.001), serum insulin levels, and activation of the GLUT4-regulated signaling pathway. Thus, increased levels of muscle sex steroids may contribute to improved fasting glucose levels via upregulation of GLUT4-regulated signaling in diet-induced obesity and hyperglycemia.

Endurance exercise training enhances local sex steroidogenesis in skeletal muscle

PURPOSE Endurance training improves skeletal muscular function including energy metabolism and structure. Sex steroid hormones partly contribute to the exercise-induced muscular adaptations. Recently, we demonstrated that skeletal muscle contains steroidogenic converting enzymes to synthesize sex steroid hormones and an acute endurance exercise activates local steroidogenesis in skeletal muscle. However, whether chronic endurance training leads to enhanced steroidogenesis in skeletal muscle is unknown. Here, we examined changes in steroidogenic enzymes and sex steroid hormones in the skeletal muscle after chronic endurance exercise training. METHODS Eleven male rats were divided into two groups: sedentary (n = 6) and trained (n = 5). Endurance training was performed on a treadmill (30 m·min(-1), 30 min) for 5 d·wk(-1) for 12 wk. The posttraining harvesting was performed 48 h after the last exercise training. RESULTS The mRNA expressions of 3β-HSD, aromatase cytochrome P450, and 5α-reductase in the skeletal muscle of trained rats were significantly higher than those of sedentary rats (P < 0.05). The protein expressions of aromatase cytochrome P450 and 5α-reductase in the skeletal muscle of trained rats were also significantly higher than those of sedentary rats (P < 0.05). The muscular dihydrotestosterone (DHT) concentrations in the skeletal muscle of trained rats were significantly higher than those of sedentary rats (P < 0.01), but there was no change in dehydroepiandrosterone, total testosterone, free testosterone, and estradiol. Furthermore, muscle weight corrected for body weight of trained rats was moderately correlated with the level of muscular DHT concentration in trained rats (r = 0.41, P < 0.05). CONCLUSIONS Endurance exercise training enhances the muscular DHT concentration through 5α-reductase in the skeletal muscle of rats, suggesting that local bioactive androgen metabolism may participate in exercise training-induced skeletal muscular adaptation.

Hormonal responses to resistance exercise during different menstrual cycle states.

PURPOSE To investigate the effect of menstrual cycle states on ovarian and anabolic hormonal responses to acute resistance exercise in young women. METHODS Eight healthy women (eumenorrhea; EM) and eight women with menstrual disorders including oligomenorrhea and amenorrhea (OAM) participated in this study. The EM group performed acute resistance exercises during the early follicular (EF) and midluteal (ML) phases, and the OAM group performed the same exercises. All subjects performed three sets each of lat pull-downs, leg curls, bench presses, leg extensions, and squats at 75%-80% of one-repetition maximum with a 1-min rest between sets. Blood samples were obtained before exercise, immediately after, 30 min after, and 60 min after the exercise. RESULTS In the EM group, resting serum levels of estradiol and progesterone in the ML phase were higher than those in the EF phase and higher than those in the OAM group. Serum estradiol and progesterone in the ML phase increased after the exercise but did not change in the EF phase or in the OAM group. In contrast, resting levels of testosterone in the OAM group were higher than those in both the ML and EF phases of the EM group. After the exercise, serum growth hormone increased in both the ML and EF phases but did not change in the OAM group. CONCLUSIONS The responses of anabolic hormones to acute resistance exercise are different among the menstrual cycle states in young women. Women with menstrual disturbances with low estradiol and progesterone serum levels have an attenuated anabolic hormone response to acute resistance exercise, suggesting that menstrual disorders accompanying low ovarian hormone levels may affect exercise-induced change in anabolic hormones in women.

MONOCYTE AND T-CELL RESPONSES TO EXERCISE TRAINING IN ELDERLY SUBJECTS

Shimizu, K, Suzuki, N, Imai, T, Aizawa, K, Nanba, H, Hanaoka, Y, Kuno, S, Mesaki, N, Kono, I, and Akama, T. Monocyte and T-cell responses to exercise training in elderly subjects. J Strength Cond Res 25(9): 2565-2572, 2011—The purpose of this study was to examine the effects of exercise training on age-related impairment of immune parameters related to T-cell activation in elderly individuals. Twenty-four elderly subjects were assigned to an exercise training group (EXC: 3 men, 9 women; age 61-76 years) or a nonexercise control group (CON: 4 men, 8 women; age 62-79 years). Subjects in EXC participated in exercise sessions 2 d·wk−1 for 12 weeks. The training session included stretching and endurance exercise (10 minutes), resistance training comprised leg extension, leg press, hip abduction, and hip adduction using exercise machine and each subjects body weight. Subjects in CON maintained their normal physical activity levels during the study period. Blood samples were collected before and after the training period. Samples were measured for the numbers of leukocytes, lymphocytes, and monocytes, and for CD3+, CD4+, CD8+, CD28+CD4+, CD28+CD8+, TRL-4+CD14+, and CD80+CD14+ cells. The number of leukocytes, lymphocytes, monocytes, CD3+, CD4+, and CD8+ cells did not change after 12 weeks in either EXC or CON. The number of CD28+CD8+ cells increased significantly after training in EXC (p ≤ 0.05), although CON showed no significant change. In the EXC group, CD80+CD14+ cell counts were significantly higher after training (p ≤ 0.05), but the TLR-4+CD14+ cell counts were unchanged. In the CON group, no significant alteration existed in TLR-4+CD14+ and CD80+CD14+ cell numbers. In conclusion, exercise training in elderly people is associated with increased CD28-expressing Tc cells and CD80-expressing monocytes. Therefore, exercise training might upregulate monocyte and T-cell-mediated immunity in elderly people.