Growth hormone (GH) and testosterone are both potent anabolic hormones, but it is not known whether they interact to positively regulate protein metabolism. To address this question, we have carried out two studies, in which we have investigated the impact of GH alone, testosterone alone and combined GH+testosterone, on whole body protein metabolism in hypopituitary men.
In the first study, ten subjects received either GH (1.5 units daily) or GH+testosterone (250 milligrams intramuscularly) for one month, and then crossed over to the alternate treatment for the second month. In the second study, nine subjects received either testosterone or GH+testosterone for one month, and then crossed over for the second month. Protein turnover was studied using a 3-hour primed-constant infusion of 1-[13C]leucine, from which rates of protein breakdown, oxidation and synthesis were estimated. Ethical approval was obtained.
GH alone increased IGF-I (7.4 plus/minus 1.0 to 24.2 plus/minus 2.7 nanomoles per litre, p<0.01), reduced protein oxidation and increased protein synthesis (p<0.05). Addition of testosterone to GH resulted in a further increase in IGF-I (to 26.4 plus/minus 2.7 nanomoles per litre, p<0.05), a further reduction in oxidation and further stimulation of synthesis (p<0.05). Testosterone alone did not alter IGF-I (11.6 plus/minus 1.2 to 11.8 plus/minus 1.2 nanomoles per litre), but reduced oxidation and increased synthesis (p<0.05). Addition of GH to testosterone increased IGF-I (to 41.0 plus/minus 4.2 nanomoles per litre, p<0.05), and resulted in a further reduction in oxidation and further stimulation of synthesis (p<0.05).
In summary, testosterone replacement in hypopituitary adults increased circulating IGF-I, only during concomitant administration of GH. Testosterone and GH exerted independent and additive effects to reduce irreversible oxidative protein loss and increase protein synthesis. We conclude that testosterone enhances the effect of GH to increase IGF-I, but exerts a protein anabolic effect that is independent of GH action.