Introduction
I think the hoopla about growth hormone (GH) started in the early 1990s from a study, by Rudman et al., that tested GH injections on old guys (aged 60-80) with low GH levels. The study lasted 12 months, with the men receiving GH for 6. They found that in men who received GH injections, there was an increase in lean body mass and decrease in adipose-tissue mass as compared to their baseline levels (Rudman et al. 1990).
There were other scattered reports around the time on the use of GH in patients with a lung condition, but otherwise, the evidence supporting the use of GH injections was scant (The results attained by Rudman and his group, however, were replicated by others.)
GH to me falls into the category of stress-associated, adaptive substance, and I think its positive effects are mediated by IGF-1, levels of which increase with GH treatment. IGF-1 promotes protein retention (positive nitrogen balance) and supports the growth and maintenance of the internal organs, bones, cartilage, etc. But the fact that GH and IGF-1 do not only act on these organs is usually lost on people. So is the realization that other changes accompany falling GH levels in the blood with aging and disease.
Somewhere along the line from GH’s humble beginnings, the reality of its effects were twisted - a reality that I think is easier to discern with context.
Early Experiments with GH
The intense fat burning effect of pituitary gland extracts was demonstrated in animals in the 1930s (Best, Campbell 1936). GH was unknown at the time, so the extracts were referred to as “ketogenic substances.” It was also appreciated that these “ketogenic” substances produced fatty liver disease in experimental animals faster than anything else (e.g. high fat diets, choline deficiency and phosphorus poisoning).
In the 1950s, around the time when the work on NEFA was progressing by the work of Dole and others, the stimulating effect of GH on NEFA mobilization was established(Raben, Hollenberg 1959).
By the early 1960s, GH was known to decrease fat stores, increase liver fat, and cause ketosis. The decrease in the respiratory quotient (RQ) (CO2 produced per molecule of O2 consumed) in response to GH provided another piece of evidence(Greenbaum 1953). The respiratory quotient in response to GH treatment was decreased to about 0.7, indicating almost pure fatty acid burning, despite the animals being provided a mixed diet.
Current Understanding of the Effects of GH
Most people know that GH has a critical role during periods of rapid growth, without which dwarfism would result. The effects of GH are particularly evident during these times, where slight insulin resistance is induced.
Clinicians who treat patients with diabetes know that rising levels of GH during the night make more insulin needed (dawn effect).
GH in men is secreted in pulses, whereas in women GH is secreted continuously at low levels; therefore the meaning of GH is probably slightly different for men and women. GH levels are highest during puberty and decreases in adulthood (I’ve heard this used as grounds for using GH injections for the purpose of becoming younger.)
In adults, the anabolic effect of GH is similar to that of insulin; but they are secreted under opposite circumstances: insulin in the fed state and GH in the fasted state.
GH, Aging and Disease
GH impairs the uptake and use of carbohydrates for energy (insulin resistance), raising blood glucose levels. Insulin secretion increases to compensate for this GH-induced insulin resistance, attendant to an increased content of intramyocellular triglycerides(Krag et al. 2007).
Moller et al. conducted a controlled study in healthy adults using high and low doses of GH where they found, among other things, that GH treatment increased renin levels (Moller, Jorgensen & Frandsen 1995). This is consistent with another study that reported a significant increase in sodium retention among GH users(Ho, Kelly 1991).
GH activates the renin-angiotensin-aldosterone system(Moller et al. 1997). Renin causes sodium and water retention and raises blood pressure. I consider renin to be a stress associated hormone, support for which is provided by the circumstances of its release. Renin also activates aldosterone, which, itself, leads to inflammation. When renin is continually activated, the fat cells and adrenal glands begin to secrete and maintain high levels of aldosterone in the blood.
The mobilization of fatty acids predisposes to lipotoxicity, impairing for instance, β-cell functioning (Winzell et al. 2003). Considering the changes that occur with aging that support the release of fatty acids, the meaning of GH is beginning to make more sense.
Conclusion
Conclusion
Of the many established age-associated metabolic changes, the effects of GH in the body mimic many of them. The continual outpouring of research on growth hormone will provide ample evidence to judge better, but for now, I don’t believe GH is a “miracle substance,” as a book I just read described it.
References
Best, C.H. & Campbell, J. 1936, "Anterior pituitary extracts and liver fat", The Journal of physiology, vol. 86, no. 2, pp. 190-203.
Greenbaum, A.L. 1953, "Changes in body composition and respiratory quotient of adult female rats treated with purified growth hormone", The Biochemical journal, vol. 54, no. 3, pp. 400-407.
Ho, K.Y. & Kelly, J.J. 1991, "Role of growth hormone in fluid homeostasis", Hormone research, vol. 36 Suppl 1, pp. 44-48.
Krag, M.B., Gormsen, L.C., Guo, Z., Christiansen, J.S., Jensen, M.D., Nielsen, S. & Jorgensen, J.O. 2007, "Growth hormone-induced insulin resistance is associated with increased intramyocellular triglyceride content but unaltered VLDL-triglyceride kinetics", American journal of physiology.Endocrinology and metabolism, vol. 292, no. 3, pp. E920-7.
Moller, J., Jorgensen, J.O. & Frandsen, E. 1995, "Body fluids, circadian blood pressure and plasma renin during growth hormone administration: a placebo-controlled study with two growth hormone doses in healthy adults", vol. 55, no. 8, pp. 663-669.
Moller, J., Moller, N., Frandsen, E., Wolthers, T., Jorgensen, J.O. & Christiansen, J.S. 1997, "Blockade of the renin-angiotensin-aldosterone system prevents growth hormone-induced fluid retention in humans", The American Journal of Physiology, vol. 272, no. 5 Pt 1, pp. E803-8.
Raben, M.S. & Hollenberg, C.H. 1959, "Effect of growth hormone on plasma fatty acids", The Journal of clinical investigation, vol. 38, no. 3, pp. 484-488.
Rudman, D., Feller, A.G., Nagraj, H.S., Gergans, G.A., Lalitha, P.Y., Goldberg, A.F., Schlenker, R.A., Cohn, L., Rudman, I.W. & Mattson, D.E. 1990, "Effects of human growth hormone in men over 60 years old", The New England journal of medicine, vol. 323, no. 1, pp. 1-6.
Winzell, M.S., Svensson, H., Enerback, S., Ravnskjaer, K., Mandrup, S., Esser, V., Arner, P., Alves-Guerra, M.C. & Miroux, B. 2003, "Pancreatic beta-cell lipotoxicity induced by overexpression of hormone-sensitive lipase", vol. 52, no. 8, pp. 2057-2065.