Increased Muscular 5α-Dihydrotestosterone in Response to Resistance Training Relates to Skeletal Muscle Mass and Glucose Metabolism in Type 2 Diabetic Rats

PLoS One. 2016 Nov 10;11(11):e0165689. doi: 10.1371/journal.pone.0165689. eCollection 2016.


Regular resistance exercise induces skeletal muscle hypertrophy and improvement of glycemic control in type 2 diabetes patients. Administration of dehydroepiandrosterone (DHEA), a sex steroid hormone precursor, increases 5α-dihydrotestosterone (DHT) synthesis and is associated with improvements in fasting blood glucose level and skeletal muscle hypertrophy. Therefore, the aim of this study was to investigate whether increase in muscle DHT levels, induced by chronic resistance exercise, can contribute to skeletal muscle hypertrophy and concomitant improvement of muscular glucose metabolism in type 2 diabetic rats. Male 20-week-old type 2 diabetic rats (OLETF) were randomly divided into 3 groups: sedentary control, resistance training (3 times a week on alternate days for 8 weeks), or resistance training with continuous infusion of a 5α-reductase inhibitor (n = 8 each group). Age-matched, healthy nondiabetic Long-Evans Tokushima Otsuka (LETO) rats (n = 8) were used as controls. The results indicated that OLETF rats showed significant decrease in muscular DHEA, free testosterone, DHT levels, and protein expression of steroidogenic enzymes, with loss of skeletal muscle mass and hyperglycemia, compared to that of LETO rats. However, 8-week resistance training in OLETF rats significantly increased the levels of muscle sex steroid hormones and protein expression of steroidogenic enzymes with a concomitant increase in skeletal muscle mass, improved fasting glucose level, and insulin sensitivity index. Moreover, resistance training accelerated glucose transporter-4 (GLUT-4) translocation and protein kinase B and C-ζ/λ phosphorylation. Administering the 5α-reductase inhibitor in resistance-trained OLETF rats resulted in suppression of the exercise-induced effects on skeletal muscle mass, fasting glucose level, insulin sensitivity index, and GLUT-4 signaling, with a decline in muscular DHT levels. These findings suggest that resistance training-induced elevation of muscular DHT levels may contribute to improvement of hyperglycemia and skeletal muscle hypertrophy in type 2 diabetic rats.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / therapy*
  • Dihydrotestosterone / analysis
  • Dihydrotestosterone / blood
  • Dihydrotestosterone / metabolism*
  • Glucose Transporter Type 4 / metabolism
  • Hyperglycemia / blood
  • Hyperglycemia / metabolism
  • Hyperglycemia / therapy
  • Insulin Resistance
  • Male
  • Muscle, Skeletal / metabolism*
  • Phosphorylation
  • Physical Conditioning, Animal
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Inbred OLETF
  • Resistance Training*


  • Blood Glucose
  • Glucose Transporter Type 4
  • Dihydrotestosterone
  • Proto-Oncogene Proteins c-akt

Grant support

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#26282199, M. Iemitsu and #15H03091, N. Mesaki). Please show the URL in this grant as follows: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Therefore, all authors have no conflict of interest.