Taking a Closer Look at the Muscles of Steroid Using Athletes… A Really Close Look

Title:Effects of anabolic steroids on the muscle cells of strength-trained athletes.

Researchers:Kadi F, Eriksson A, Holmner S, Thornell LE Department of Integrative Medical Biology, Umea University, Sweden.

Source:Med Sci Sports Exerc 1999 Nov;31(11):1528-34

Summary:

Athletes who use anabolic steroids get larger and stronger muscles. How this is reflected at the level of the muscle fibers has not yet been established and was the topic of this investigation. METHODS: Muscle biopsies were obtained from the trapezius muscles of high-level power lifters who have reported the use of anabolic steroids in high doses for several years and from high-level power lifters who have never used these drugs. Enzyme-immunohistochemical investigation was performed to assess muscle fiber types, fiber area, myonuclear number, frequency of satellite cells, and fibers expressing developmental protein isoforms.

RESULTS: The overall muscle fiber composition was the same in both groups. The mean area for each fiber type in the reported steroid users was larger than that in the nonsteroid users (P < 0.05). The number of myonuclei and the proportion of central nuclei were also significantly higher in the reported steroid users (P < 0.05). Likewise, the frequency of fibers expressing developmental protein isoforms was significantly higher in the reported steroid users group (P < 0.05).

CONCLUSION: Intake of anabolic steroids and strength-training induce an increase in muscle size by both hypertrophy and the formation of new muscle fibers. We propose that activation of satellite cells is a key process and is enhanced by the steroid use. The incorporation of the satellite cells into preexisting fibers to maintain a constant nuclear to cytoplasmic ratio seems to be a fundamental mechanism for muscle fiber growth. Although all the subjects in this study have the same level of performance, the possibility of genetic differences between the two groups cannot be completely excluded.

Discussion:

This study was trying to answer one basic question, “How do anabolic steroids produce muscle growth?” If you were to ask the average bodybuilding enthusiast I think you would hear, “they increase protein synthesis.” This is not untrue, its just that it is only part of the answer. In fact, the answer must include virtually every mechanism involved in skeletal muscle hypertrophy. These include:

• Enhanced growth factor activity (e.g. GH, IGF-1, etc.)
• Enhanced activation of myogenic stem cells (i.e. satellite cells)
• Enhanced myonuclear number (to maintain nuclear to cytoplasmic ratio)
• Enhanced protein synthesis
• New myofiber formation

You can read more about these mechanisms in my paper, Advanced Training Planning for Bodybuilders. Now, where do androgens fit in to this? Starting with growth factor activity, we know that testosterone increases GH and IGF-1 levels. In a recent study by Fryburg (Fryburg, 1997) the effects of testosterone and stanozolol were compared for their effects on stimulating GH release. Testosterone enanthate (only 3 mg per kg per week) increased GH levels by 22% and IGF-1 levels by 21% whereas oral stanozolol (0.1mg per kg per day) had no effect whatsoever on GH or IGF-1 levels. This study was only 2-3 weeks long, and although stanozolol did not effect GH or IGF-1 levels, it had a similar effect on urinary nitrogen levels. What does this difference between testosterone and stanozolol mean? In my opinion it means that stanozolol can increase protein synthesis by binding to AR receptors in existing myonuclei, however, because it does not increase growth factor levels it is ineffective at activating satellite cells and therefor may not increase satellite cell activity and thus myonuclear number.

Enhanced activation of satellite cells requires IGF-1. Those androgens that aromatize are effective at not only increasing IGF-1 levels but also the sensitivity of satellite cells to growth factors (Thompson, 1989). This action has no direct effect on protein synthesis.It leads to a greater capacity for protein synthesis by increasing fusion of satellite cells to existing fibers. This increases the number of myonuclei and therefore the capacity of the cell to produce proteins.

So it is not only that testosterone increases protein synthesis by activating genetic expression, it also increases thecapacityof the muscle to grow in the future by leading to the accumulation of myonuclei which are required for protein synthesis. There is good reason to believe that testosterone in high enough doses may even encourage new fiber formation. To quote the authors of this study:

“Intake of anabolic steroids and strength-training induce an increase in muscle size by both hypertrophy and the formation of new muscle fibers. We propose that activation of satellite cells is a key process and is enhanced by the steroid use.”

Just a note for those of you who will use androgens but refuse to use supplements. There is good evidence that creatine specifically stimulates the formation of myofibrillar protein in newly developing fibers (Ingwall, 1972; 1974; 1975; 1976). The effect is concentration dependent, maxing out at about 250 µM. Normal plasma concentrations are about 100 µM. In my opinion, creatine supplementation is certainly called for in athletes using heavy androgens.

A separate argument related to this study

I would like to quickly address a separate issue related to steroid use. Although I believe Bill Roberts has competently addressed this issue previously in earlier issues of MESO-Rx, I would like to make my own contribution here. It has been thought, and is still commonly believed, that using steroids decreases the number of “steroid” receptors. This argument is used to explain the fact that growth eventually stops while using a given amount of steroid. Once you understand all of the effects of testosterone on growth factor levels and muscle cells you come to realize that the opposite is in fact the case. Simply stated, supraphysiological levels of testosterone gives rise to increased numbers of myonuclei and thereby an increase in the number of total androgen receptors per muscle fiber. Therefor, the larger you get from using steroids, the more receptive your muscle become to the presence of testosterone. Keep in mind that I am referring to testosterone and testosterone esters. Not theneutereddesigner androgens that people take to avoid side effects (Fryburg, 1997). This is not an argument to rapidly increase the dosages you use. It takes time for these changes to occur and the benefits of higher testosterone levels will not be immediately realized.

Fryburg DA., Weltman A., Jahn LA., et al: Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone releasing hormone-stimulated GH secretion in healthy men: Impact of gonadal steroid and GH secretory changes on metabolic outcomes.J Clin Endocrinol. Metab. 82(11):3710-37-19, 1997

Thompson SH., Boxhorn LK., Kong W., and Allen RE. Trenbolone alters the responsiveness of skeletal muscle satellite cells to fibroblast growth factor and insulin-like growth factor-I.Endocrinology. 124:2110-2117, 1989.

Ingwall JS, Morales MF, Stockdale FE, Wildenthal K. Creatine: a possible stimulus skeletal cardiac muscle hypertrophy.Recent Adv Stud Cardiac Struct Metab1975;8:467-81

Ingwall JS, Morales MF, Stockdale FE. Creatine and the control of myosin synthesis in differentiating skeletal muscle.Proc Natl Acad SciU S A 1972 Aug;69(8):2250-3

Ingwall JS, Weiner CD, Morales MF, Davis E, Stockdale FE. Specificity of creatine in the control of muscle protein synthesis.J Cell Biol1974 Jul;62(1):145-51

Ingwall JS, Wildenthal K. Role of creatine in the regulation of cardiac protein synthesis.J Cell Biol1976 Jan;68(1):159-63