Why anabolic hormones do not play a role in skeletal muscle hypertrophy.
Imagine a total stranger walked up to you, knowing you stay up to date on current strength and conditioning and fitness knowledge, and preceded to tell you that the increase in the big three anabolic hormones Growth Hormone(GH), Testosterone(T), and Insulin like Growth Factor (IGF-1) associated with resistance training has nothing to do with hypertrophy. You, like me, would probably drop your jaw and demand to see studies, or at least have someone explain it to you!
Hypertrophy is defined as an increase in cross sectional area of a muscle cell. There are two types of hypertrophy; myofibrillar and sarcoplasmic. Myofibrillar hypertrophy is an increase in the number of the contractile units; actin and myosin (we might find titin in this classification soon). These contractile units are highly organized and arranged in parallel series. Myofibrillar hypertrophy allows for more contractile units to be packed into a single muscle cell, leading to an increase in the amount of cross bridging. This, among other adaptations, will increase the total force a muscle produces. Myofibrillar hypertrophy is an adaptation generally associated with, but not limited to, high intensity-low volume training (training for strength and power). Sarcoplasmic hypertrophy, on the other hand, is an increase in the noncontractile units within a muscle. It is an adaptation associated with moderate to low intensity training with decreased time between sets (training for hypertrophy and endurance).
For years numerous researchers including Bill Kraemer, Michael Stone, and Andrew Fry, studied affects of different anaerobic and aerobic modalities on hormone levels. Results from countless studies have shown a correlation between intensity and time between sets, and specific anabolic hormones that coincide with each form of training. In terms of resistance training the specific hormonal responses were thought to be one of primary reason for the increases in hypertrophy. For a great review on all this literature check out “The Mechanisms of Muscle Hypertrophy and Their Application to Resistance Training” by Brad Shoenfeld (JSCR 2010).
For years, we have had tons of quality literature being produced showing the role of GH, T, and IGF-1 on muscle hypertrophy. It would be safe to say that the general consensus is that improvements in hypertrophy are mostly due to an increase in anabolic hormones.
What if new research being published actually indicates that anabolic hormones do not influence hypertrophy?
THE ROLE OF ANABOLIC HORMONES IN HYPERTROPHY AND RESISTANCE TRAINING
Testosterone is one of the most important hormones within our bodies. It is acutely and chronically affected by countless body functions. Testosterone is a steroid hormone, meaning it has a cholesterol back bone, allowing it to cross the lipid bi-layer of the sarcolemma (outer layer a muscle cell). Once inside, it enhances protein transcription, increasing protein accretion. This powerful hormone has also been shown to decrease protein breakdown, improve production of IGF-1, and improve the reutilization of aminos to increase protein synthesis. Pharmacological doses have been shown to improve protein synthesis (Griggs et al 1986). Finally, there has been a link between testosterone and the ability to activate DNA needed for growth of satellite cells (Sinha-Hikim et al 2003).
Growth hormone, another anabolic hormone, came to light over the past 10 years thanks to Mark McGuire, Barry bonds, Sean Merriman, and other pro athletes. Growth Hormone and IGF-1 have an inverse relationship in the musculoskeletal system along the IGF-1 GH axis. An excess amount during growth leads faster changes in stature while a deficiency leads to slower changes. (Florini et al 1996). GH has been shown to play a pivotal role in body composition for adults who are GH deficient. Studies have found an increase in whole body protein synthesis, however there was no change in specific muscle protein synthesis (Yarashesk et al 1993). Studies have also found an increase in collagen synthesis, as well as an increase in osteoblasts, suggesting a potential to increase bone remodeling (Brixen et al 1990). There are documented increases in Lean Body Mass and weight gain with GH supplementation; however, this could also be due to the water retention associated with GH supplementation (Yarashesk et al 1993).
NATURAL ELEVATION OF ANABOLIC HORMONES
Most male high school students are pumped full of anabolic hormones. Any halfway decent exercise program and proper diet (in most teenager’s case just enough calories) will cause an increase in hypertrophy. This appears to support the role of anabolic hormones and hypertrophy. But wait, let’s think for a minute, is there really a time in your life that you will NATURALLY have that much testosterone running through your body? (669 ng/dl @25-30yrs, 621 ng/dl @35-39yrs,) The answer is no. Now, females on the other hand produce 1/10th (65 ng/dl) of the testosterone that their male counterparts produce. That means that men produce 10x more testosterone then women, yet women see increases in hypertrophy at the same rate as males (Cureton et al 1988). It’s possible that females need less testosterone than males to induce hypertrophy, but research is scarce and no study has actually tested it. That leads us to an interesting thought: maybe testosterone and other anabolic hormones don’t play as much of a role as we once thought.
THE NEW ROLE ANABOLIC HORMONES PLAY IN HYPERTROPHY AND RESISTANCE TRAINING
Let’s get down to business. If you are not a teenage ball of hormones or someone taking a steroid supplement, pay close attention to what I’m about to say…The increase in anabolic hormones from resistance training does not increase muscle protein synthesis and hypertrophy. The increased testosterone and growth hormone you have circulating after performing multi-joint exercises first may not help you with the following lifts, or increase protein synthesis!
Within the past two years, two studies have been published bringing these results to life. These are the first studies to test the relationship between anabolic hormones and hypertrophy. As you can guess, the results are pretty shocking. The first study tested whether a single exercise trial at a high or low hormone state had a greater effect on protein synthesis of the bicep brachii. The first trial, the low hormone state (LH), consisted of an arm curl for four sets of ten reps at 95% of subjects 10 RM with 120s rest between sets. Trial two, the high hormone state (HH), consisted of the same arm curl protocol immediately followed the leg press for five sets of ten reps at 90% of subjects 10RM, 60s between sets, trying to create an elevated hormone state. Subjects were provided with a protein supplement post training to supply essential AA needed for protein synthesis. Results found an increase in circulating T, GH, and IGF-1 during trial 2 (HH) but NO difference between groups in protein synthesis post exercise.
The second study used the same LH and HH exercise protocol, but extended it to 15 weeks (3d/wk for weeks 1-6, 4d/wk for weeks 7-15). Similar to the first study the HH group had a significant increase of IGF-1 (1.8*increase), T, and GH (8*increase) post exercise compared to the LH group. Myofibrillar protein synthesis increased by 78% for the LH group and 61% for the HH group (p < 0.05)! There was also no differences between 10RM strength and 1RM strength between groups, but a significant difference in increase of Maximal Voluntary Contraction between groups (LH 20±4%, range 3%-49% vs. HH 19±3%, range 2-34%), and no difference in cross sectional area between groups. (LH 12±2% and HH 10±2%). This study shows that even fifteen weeks of a bicep curl in a LH state is more effective then completing a bicep curl in a HH state. The results contradict the current ideas, and show that completing a multi joint exercise on the same day as assistance exercise will increase in anabolic hormone production BUT this does not increase hypertrophy and protein synthesis.
THE REAL CAUSES FOR HYPERTROPHY
These studies question common training principles. Yes, a heavy multi-joint lift that recruits a lot of musculature during a workout will cause an increase in the release of anabolic hormones. Yes, decreased time between sets will increase GH production. Yes, manipulating loads and rest will increase the amount of circulating T, GH, IGF-1. However, the increase in hormones being released does not directly increase protein synthesis or hypertrophy.
So what actually causes hypertrophy? Well, it seems as if myofibrillar hypertrophy and protein synthesis are based solely upon local factors that activate intracellular signaling pathways. The first two pathways I will describe are calcium dependent. The first pathway is Calcineurin: Calcium dependent signaling pathway. Calcineurin dephosphorylates cytoplasmic proteins, allowing the proteins to be translocated into the nucleus for gene transcription. (Olsen 2000) This pathway has been shown to be responsible for cardiac hypertrophy and research is controversial as to whether it causes hypertrophy in skeletal muscle. On a side note based on the low amplitude calcium signaling, it is hypothesized that the gene transcription associated with this pathway has the potential to affect muscle phenotype(Olsen 2000). The next pathway is the Calcium Calmodulin Protein Kinase signaling pathway. This pathway similar to the previous is regulated by intracellular calcium; however it is regulated by short intensity high amplitude calcium signals.(Olsen 2000) Similar to Calcineurin, literature is incomplete when explaining the role calcium Calmodulin plays in muscle growth and phenotype transitions. (Olsen 2000) (Below is a visual of how the two pathways effect gene transcription.)
The most supported intracellular pathway responsible for muscle hypertrophy is the IGF-1, AKT-mTOR-p70(56k) pathway. This pathway appears to be dependent on IGF-1 binding along the cell membrane. IGF-1 activates a series of kinases, with the end product being an increase in protein synthesis, as described in the image below. (Glass 2003) Studies that have blocked this pathway led to extreme atrophy in rats (this would be impossible to get through an IRB with human subjects).To further support the importance of this pathway, the first study mentioned above measured the expression of p70(56k), STAT-3, p-eEF2, and p-JAK2, following exercise trials (West 2009). As expected there was no significant difference between resting and post exercise measures for any proteins in the HH and LH group.
These studies bring to light a new way to picture hypertrophy and protein synthesis. Before these studies, most people would tell you the cause of hypertrophy was due to increased anabolic hormones T, GH, and IGF-1. I was in the same boat until I stumbled upon this research and dove into every article I could find relating to the topic. And it is clear, muscle hypertrophy is multi-faceted, but we are shifting away from the anabolic hormone trend.
It is hard to change 20+ years of teaching because of the results of a couple studies, but that is the beautiful thing about the field we’re in; it is ever changing.
I once told a group of students that this field is a ton of fun, and can be very frustrating. What you thought was fact and explained one day, could be old news within a year. It is important to keep an open mind as the field continues to grow and evolve. It is our job, whether you’re a strength coach, personal trainer, researcher, and professor to continue to not only stay up to date but also not always believe everything we hear. Just imagine if we did, we’d all be squatting and lunging on BOSU balls claiming it’s the best way to increase power output!
TAKE HOME MESSAGES
Hypertrophy does not appear to be effected by the increase of Testosterone, Growth Hormone, and IGF-1, as a result of the exercises selected.
It does appear that hypertrophy is dependent of intracellular pathways involving STAT3, eEF2, and p70S6K. These proteins increase protein translation, synthesis, and have the ability to cause a shift in muscle phenotype.
Keep an open mind! Our field is always changing!
Work Cited
Brixen K, Nielsen HK, Mosekilde L, Flyvbjerg A. A short course of recombinant human growth hormone treatment stimulates osteoblasts and activates bone remodeling in normal human volunteers. J Bone Miner Res. 1990;5(6):609–618.
Cureton KJ, Collins MA, Hill DW, McElhannon FM. Muscle Hypertrophy in men and women. Med Sci Sports Exerc. 1988 Aug;20(4):338-44.
Ferrando AA, Tipton KD, Doyle D, Phillips SM, Cortiella J, Wolfe RR. Testosterone injection stimulates net protein synthesis but not tissue amino acid transport. Am J Physiol. 1998;275:E864–E871.
Florini JR, Ewton DZ, Coolican SA. Growth hormone and the insulin-like growth factor system in myogenesis. Endocr Rev. 1996;17(5):481–517.
Glass DJ. Review: Molecular mechanisms modulating muscle mass. Trends Molec Med 2003;9:344-350
Griggss R, Challiday D, Kingston W, Moxley RT. Effect of testosterone on muscle protein synthesis in myotonic dystrophy. Ann. Neurol. 1986;20(5):590-596
Olsen EN, Williams RS, Calcineurin signaling and muscle remodeling. Cell 2000;101:S67-S79
Shoenfeld, B The Mechanisms of Muscle Hypertrophy and Their Application to Resistance Training. JSCR 24:10,2857-2872, 2010
Sinha-Hikim I, Roth SM, Lee MI, Bhasin S. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab. 2003;285(1):E197–E205.
Simon, D., Nahoul, K., & Charles M.A. (1996). Sex Hormones, Aging, Ethnicity and Insulin Sensivity in Men: An Overview of the TELECOM Study. In Vermeulen, A. & Oddens, and B. J. (Eds.), Androgens and the Aging Male (pp. 85-102).
West DW, Kujbida GW, Moore DR, Atherton P, Burd NA, Padzik JP, De Lisio M, Tang JE, Parise G, Rennie MJ, Baker SK, and Phillips SM. Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men. J Physiol 587: 5239-5247, 2009.
West DW and Phillips SM. Anabolic processes in human skeletal muscle: restoring the identities of growth hormone and testosterone. Phys Sportsmed 38: 97-104, 2010.
West DW, Burd NA, Tang JE, Moore DR, Staples AW, Holwerda AM, Baker SK, and Phillips SM. Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors. J Appl Physiol 108: 60-67, 2010.
Yarasheski KE, Zachweija JJ, Angelopoulos TJ, Bier DM. Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters. J Appl Physiol. 1993;74(6):3073–3076.