Muscle Androgen Receptor Content but Not Hormones Determine Exercise Response

[madman]

Muscle Androgen Receptor Content but Not Systemic Hormones Is Associated With Resistance Training-Induced Skeletal Muscle Hypertrophy in Healthy, Young Men


The factors that underpin heterogeneity in muscle hypertrophy following resistance exercise training (RET) remain largely unknown. We examined circulating hormones, intramuscular hormones, and intramuscular hormone-related variables in resistancetrained men before and after 12 weeks of RET. Backward elimination and principal component regression evaluated the statistical significance of proposed circulating anabolic hormones (e.g., testosterone, free testosterone, dehydroepiandrosterone, dihydrotestosterone, insulin-like growth factor-1, free insulin-like growth factor-1, luteinizing hormone, and growth hormone) and RET-induced changes in muscle mass (n = 49). Immunoblots and immunoassays were used to evaluate intramuscular free testosterone levels, dihydrotestosterone levels, 5α-reductase expression, and androgen receptor content in the highest- (HIR; n = 10) and lowest- (LOR; n = 10) responders to the 12 weeks of RET. No hormone measured before exercise, after exercise, preintervention, or post-intervention was consistently significant or consistently selected in the final model for the change in: type 1 cross sectional area (CSA), type 2 CSA, or fat- and bone-free mass (LBM). Principal component analysis did not result in large dimension reduction and principal component regression was no more effective than unadjusted regression analyses. No hormone measured in the blood or muscle was different between HIR and LOR. The steroidogenic enzyme 5α-reductase increased following RET in the HIR (P < 0.01) but not the LOR (P = 0.32). Androgen receptor content was unchanged with RET but was higher at all times in HIR.Unlikeintramuscular free testosterone, dihydrotestosterone, or 5α-reductase, there was a linear relationship between androgen receptor content and change in LBM (P < 0.01), type 1 CSA (P < 0.05), and type 2 CSA (P < 0.01) both pre- and post-intervention. These results indicate that intramuscular androgen receptor content, but neither circulating nor intramuscular hormones (or the enzymes regulating their intramuscular production), influence skeletal muscle hypertrophy following RET in previously trained young men.


CONCLUSION

We performed backward elimination and principal component regression on a relatively large cohort (n = 49) of resistance-trained men and conclude that the post-exercise AUC (i.e., acute transient net hormonal exposure) and resting hormone concentrations measured in the blood do not share common variance with RET-induced changes in muscle mass. That is, systemic hormone concentrations are not related to, or in any way predictive of, RET-induced changes in muscle mass. Performing subset analysis on the highest- and lowest responders revealed that androgen receptor content, not intramuscular androgen levels, does not change with RET in trained participants but is significantly higher in HIR than LOR to RET. This study, in conjunction with others (Bamman et al., 2007; Petrella et al., 2008; Davidsen et al., 2011; Eynon et al., 2013), provides evidence that the relative increase in skeletal muscle mass following RET is underpinned by local intramuscular factors and not systemic hormonal concentrations.

 

[madman]

2013 paper

Are Acute Post–Resistance Exercise Increases in Testosterone, Growth Hormone, and IGF-1 Necessary to Stimulate Skeletal Muscle Anabolism and Hypertrophy?




Contrasting Perspectives


PREVAILING PERSPECTIVE
Acute post–resistance exercise (RE) increases in anabolic hormones may not be ‘‘necessary’’ to stimulate skeletal muscle anabolism and hypertrophy; however, as we will support in the following discussion, post-RE increases in these hormones are ‘‘optimal’’ for maximizing skeletal muscle anabolism and hypertrophy. For purposes of this presentation, increases in testosterone (T) and growth hormone (GH) will also imply increases in insulin like growth factor 1 (IGF-1) (22,24). Furthermore, we will limit the discussion of these adaptations to men, while recognizing that training variables such as training history, mode, intensity, volume, and rest interval (RI) length in between sets will have a compelling influence on the hormonal responses to RE.



CONCLUDING STATEMENT
The anabolic hormonal milieu is necessary to maximize functional adaptations to RT. Although post-RE elevations in anabolic hormones may not be necessary to acutely stimulate muscle protein synthesis or promote hypertrophy of small muscle masses, these elevations in anabolic hormones are ideal to optimize functional performance gains in whole body skeletal muscle mass and strength in men and women across the lifespan.


E. Todd Schroeder Matthew Villanueva University of Southern California Division of Biokinesiology & Physical Therapy Los Angeles, CA


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CHALLENGING PERSPECTIVE
A pervasive view in the area of endocrine responses to resistance exercise is that acute postexercise hormonal responses of testosterone, growth hormone (GH), and insulin-like growth factor 1 (IGF-1) are critical for subsequent skeletal muscle anabolism. If this is the case, then exercise regimes can be manipulated to enhance hormonal responses and thus enhance skeletal muscle adaptations such as strength and muscle mass gain. Despite this alluring prospect, we contend that post-exercise increases in testosterone, GH, and IGF-1 are not necessary to stimulate skeletal muscle anabolism and hypertrophy and that measurement of the responses of these hormones yields little in the way of insight into longer-term resistance training-related adaptation.





CONCLUDING STATEMENT
It is time to write the requiem for studies that measure only postexercise hormonal responses and infer a potential effect on hypertrophy. We find that the evidence for such an assertion lacking and causal interpretation unwarranted given the lack of evidence that exercise induced hormones are important in regulating hypertrophy after resistance exercise. Moreover, pharmacologic ablation and exogenous androgen administration are not appropriate models from which to draw conclusions about the effect of exercised-induced changes in hormonal concentrations on hypertrophy.


Daniel W. D. West Stuart M. Phillips McMaster University Department of Kinesiology Exercise Metabolism Research Group Hamilton, Ontario, CANADA

 

[Nelson Vergel]

This may be the reason some men respond better at the gym than others with the same hormone levels: their androgen receptor inside their muscles content is higher.

 

[Sean Mosher]

I would assume this is referring to receptor site sensitivity then, correct?
I believe this is why many of the more progressive TRT docs are more willing to push the dose if need be to resolve symptoms as opposed to worrying exclusively about numbers.

 

[madman]

I would assume this is referring to receptor site sensitivity then, correct?
I believe this is why many of the more progressive TRT docs are more willing to push the dose if need be to resolve symptoms as opposed to worrying exclusively about numbers.

Androgen receptor content.....the study was of healthy young men.

If anything I would say desensitization of the AR would be seen in some older men or men that have used/abused testosterone/AAS as oppose to healthy young males.