interesting stuff on cellular level effects

[candidizzle]

Glucocorticoids inhibit the physiological secretion of growth hormone (GH) and appear to reduce IGF-I activity at target organs – alterations of steroid-induced glutamine synthetase represent a potential mechanism of action, and dose-dependent inhibition of glutamine synthetase was seen using IGF-I in rat L6 cells (Sacheck et al. 2004).

Evidence using a myoblast cell line has shown that exogenous GH appears to induce GH-receptor activation, IGF-I mRNA production, phosphorylation of JAK2, Stat5a, 5b and increases in suppressor of cytokine signalling-2 (SOCS-2; Sadowski et al. 2001, Frost et al. 2002).

IGF-I is the only factor known to accelerate both satellite cell proliferation and differentiation and mice transgenically overexpressing IGF-I have significantly higher muscle mass than controls (Hayashi et al. 2004, Shavlakadze et al. 2005), whilst IGF-II appears to have an important developmental role and has higher specificity for the differentiating capacity of muscle (Florini et al. 1996).


The key cellular vector for androgen-associated muscle hypertrophy appears to be the satellite cell (Chen et al. 2005).

There is increasing evidence of androgen action in muscle interacting with IGF-I. In rat diaphragmatic muscle, a dose-dependent increase in IGF-I mRNA expression occurred following exposure to androgen (Lewis et al. 2002). When harvested bovine male satellite cells were treated with various androgen concentrations (using trenbolone), a dose-dependent increase in IGF-I mRNA expression occurred (Kamanga-Sollo et al. 2004). As yet no data have been generated demonstrating a distinction in dynamics of specific IGF-I isoforms upon androgen administration. Androgenic activity may be directly linked to the IGF-I signalling system with p70s6kinase, found downstream of the Akt/mTOR pathway, a candidate for early evidence is emerging (Xu et al. 2004). A proportion of the anabolic effects of androgens may also be anti-catabolic via an anti-glucocorticoid action (Danhaive & Rousseau 1988, Zhao et al. 2004).

In a study of ten older men sequentially exposed to testosterone; GH or both, muscle IGF-I gene expression rose 1.9-fold in the GH group and by 2.3-fold in the testosterone+GH groups (Brill et al. 2002).


http://joe.endocrinology-journals.org/cgi/content/full/191/2/349