RESEARCH UPDATE: GH HAS DIRECT ANABOLIC ACTIONS ON MUSCLE INDEPENDENT OF IGF-1

The anabolic action of GH has been exploited to increase lean body mass and protein synthesis however; the mechanisms of GH anabolic actions on skeletal muscle are not fully understood. The growth-promoting actions of GH are though to be mediated by circulating or locally produced insulin-like growth factor 1 (IGF-1), which is a critical agent involved in muscle growth5,6.  Acute resistance exercise has been shown to increase blood levels of both GH and IGF-1 which may be an important physiological adaptation to building muscle9.  For example, in one study, the GH responses during exercise and during the recovery period in trained and sedentary young men were compared. The GH levels were higher during exercise and in recovery in trained athletes compared to the sedentary controls.  This increase of GH in the trained athletes may represent an important endocrine adaptation to training and building muscle. Additionally, studies have reported that GH is taken up directly by human skeletal muscle during exercise23.  This direct uptake of GH may contribute to the acute increases in muscle protein synthesis that occurs during exercise as GH acutely stimulates muscle protein synthesis in muscle.  In this month’s journal of Clinical Endocrinology and Metabolism, researchers examined how GH affects protein synthesis when produced in excess and what happens when GH is suppressed.  They compared patients with pituitary disorders whom produce excess GH (Gigantism) and compared them to normal people.  Patients with excess GH had increased rates of protein synthesis compared to normal people but protein breakdown was the same between the groups.  This is similar to a previous research reporting that GH stimulates muscle protein synthesis yet has no effect on muscle tissue breakdown.  Interestingly, researchers examined protein synthesis rates in the gigantism patients undergoing GH suppression therapy to control excess GH and found that GH suppressive therapy resulted in a reduction in protein synthesis and lean mass with GH suppressive therapy31. 
  For a long time, many researchers have attributed the anabolic effects of GH to increases in circulating IGF-1 levels, but new research has reported direct anabolic effects of GH on muscle.  In this month’s journal of Proc. Natl. Acad. Sci. U S A researchers reported that GH has direct anabolic actions on muscle independent of IGF-18.  The researchers reported that GH leads to an increased muscle fiber number, indicating that GH has direct actions of muscle.  GH was found to increase the size of muscle fibers by acting on a specific feature called muscle cell fusion (the process of turning immature muscle fibers develop into mature muscle fibers).  In conclusion, a few important finding were reported: 1.) GH has direct anabolic actions on muscle 2.) GH and IGF-1 muscle enhancing effects are additive and rely on different signaling pathways.  Taken together, the data reveals that GH has specific function in the control of muscle cell fusion, an essential process for muscle growth. 

Growth Hormone Receptor Regulation

It’s now clear that GH is having some direct effects on muscle itself that are acting independently of IGF-1.  Furthermore, the direct effects of GH on muscle have been documented as a single dose of GH can lead to an increase in mRNA IGF-1 expression (a powerful local muscle growth factor)26. As mentioned previously, GH seems to work best when combined with other anabolics such as IGf-1.  For example, when researchers want to test how anabolic an agent is they put mice on what’s called hindlimb suspension (This is equivalent to putting a human leg in a cast, it’s a model that produces rapid muscle atrophy or loss).   Researchers placed rats in hindlimb suspension and then had them contract their leg muscles and administered GH, IGF-1, or a combination of GH and IGF-1.  The group that received both GH and IGF-1 effectively prevented muscle atrophy compared to either group alone12.  The rise in GH that occurs during exercise may be important for GH receptor regulation as GH receptors are found in muscle and may be an important adaptation to increasing muscle mass.  In fact age-related reductions of GH binding proteins levels, which reflect diminished GH receptor status has been observed in older adults13.  One study reported that in healthy older men, the two biggest factors that contributed to reduced muscle mass in healthy older men was increased muscle myostatin levels (myostatin suppresses muscle growth) and reduced GH receptor number in muscle17.  In a similar study to the previous study mentioned above, researchers put mice with their legs on hindlimb suspension and looked specifically at the GH receptor in muscle.  GH receptor in muscle was increased in muscle by 406% in type I muscle and 90% in type II muscle after 7 days of muscle unloading.  The researchers speculated that the increase in GH receptor concentration was due to prevent further atrophy and increase anabolic activity in muscle.  So what happens after you damage muscle tissue when you go to the gym?  GH receptor increases in regenerating muscle cells after muscle damage, as GH is important for the early phase of muscle regeneration24, 25, 27.  So now that you know that GH has direct actions on muscle, there is no better way to increase GH than hardcore training.


SEEING LITTLE BIRDS AFTER A SET = GOOD GH SECRETION
    Want to know if you are getting a good increase in GH during exercise without taking blood samples?  If you feel like the last set you did was going to make you pass out from exhaustion then chances are you have a good spike in GH.  Here is a cool little research study where researchers reported that GH levels during exercise are related to work perception or how hard you feel like you are working.  Kjaer et al15. investigated the mechanisms responsible for the regulation of GH secretion during exercise in healthy male subjects. So how do you alter someone’s perception of how hard they are working out in the gym?  The researchers administered a drug which weakened skeletal muscle contractions by blocking muscle nerve transmission!  Basically, it makes lifting the barbell feel like you were maxing out!!  The authors report that the GH level is closely related to perceived exercise intensity (how hard you feel you are working out) and not to the actual workload carried out. Makes sense, as the GH responses to short, high intensity resistance exercise with moderate weights which produce large increases in lactic acid, produce greater GH responses than maxing out with singles, heavier weight, and longer rest periods.  Additionally, the use of forced reps which allows a person to perform a greater than normal workload has been shown to increase GH to a greater extent than performing a regular set28…so crank up your intensity to increase your GH.