Testosterone, IGF-1, and Training

Title: Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans.

Researchers: Bamman MM, Shipp JR, Jiang J, Gower BA, Hunter GR, Goodman A, McLafferty CL Jr, Urban RJ.

Institution: Department of Surgery, University of Texas Medical Branch, and 2 Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas 77550 Source: American Journal of Physiology Endocrinology & Metabolism. 2001 Mar;280(3):E383-90.

Summary: These investigators looked at the effects of concentric (CON) reps vs. eccentric (ECC) reps on muscle insulin-like growth factor-1 (IGF-I) mRNA concentration. They hypothesized a greater IGF-I response after ECC compared with CON.

Methods: Ten healthy subjects (Average age 24.4 yrs) completed eight sets of eight CON or ECC squats separated by 6-10 days. IGF-I, IGF binding protein-4 (IGFBP-4), and androgen receptor (AR) mRNA concentrations were determined in vastus lateralis from muscle biopsy before and 48 h after ECC and CON. Serum total testosterone (TT) and IGF-I were measured serially across 48 h, and serum creatine kinase activity (CK), isometric maximum voluntary contraction (MVC), and soreness were determined at 48 h.

Results: IGF-I mRNA concentration increased 62% and IGFBP-4 mRNA concentration decreased 57% after ECC. The direction of these changes after CON were similar but not statistically significant. AR mRNA concentration increased after ECC (63%) and CON (102%). Serum levels of total testosterone and IGF-I showed little change. MVC fell 10% and CK rose 183% after ECC squats. Perceived soreness was higher after ECC compared with CON.

Conclusion: Results indicate that a single bout of mechanical loading in humans alters activity of the muscle IGF-I system, and the enhanced response to ECC suggests that IGF-I may somehow modulate tissue regeneration after mechanical damage.

Discussion: Nothing in this study should really surprise us. But it does shed light on how lifting weights selectively regulates anabolic activity to specific tissues of the body. Training increased both androgen receptors as well as muscle specific IGF-1.

Training causes an increase in androgen receptors (testosterone receptors) on muscle cells, which increases the sensitivity of your muscle to your natural testosterone levels. This effect of training on androgen receptors is specific to muscle tissue. In other words, you are not going to see an increase in the effects of testosterone in other tissues such as your hair or your skin. So unlike using steroids, training only increases the effects of testosterone in muscle tissue.

IGF-1 is another critical player in muscle growth. Muscle growth from weight training is the result of IGF-1 being produced by the muscle cells themselves, not the liver. In fact, IGF-1 from the liver is genetically different from IGF-1 produced in your muscles. This is the reason why using IGF-1 systemically (from the blood stream) has been a hit and miss proposition.

IGF-1 formation in muscle tissue is absolutely critical if significant muscle hypertrophy is to occur. IGF-1 produced inside muscle cells that have been damaged by heavy training, oozes out of the cell and activates satellite cells. These satellite cells then donate nuclei to the damaged muscle cell, thereby allowing it to grow larger than before. There is a limit to the size of a muscle cell, and it depends largely on the number of nuclei it has. If you prevent a muscle cell from getting more nuclei from satellite cells, it simply will not grow, no matter how heavy things get. (1,2,3) The reduction in IGF binding protein-4 (IGFBP-4) leads to increased IGF-1 activity.(4) [Note: IGFBP-"3" also binds IGF-1 but in a good way. IGFBP-3 is the main carrier of IGF-1 and prolongs the half-life of IGF-1]

I would like to voice my strongly held opinion that the ever so slight changes in systemic hormone levels as a result of exercise are not responsible for the muscle growth observed with resistance exercise. Instead, as this study illustrates, it is the changes that occur within the muscle cells themselves that account for any hormonal contributions to hypertrophy. Both an increase the muscle's sensitivity to existing androgen levels, increases in intracellular IGF-1 levels, with concomitant decreases in inhibitory IGF binding proteins are the primary "hormonal" mechanisms for muscle growth as a result of training (excluding the use of exogenous hormones).

Reference: http://www.hypertrophy-specific.com/HSreport/iss01/