Growth Hormone/IGF-1 Signaling Pathway Transduction

Growth hormone (GH), which is also known as somatotropin, and insulin-like growth factor 1 (IGF-1 or IGF-I) exert a myriad of pleiotropic effects via a number of similar and distinct intracellular signalling pathways.

The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay aging.

One of the main actions common to GH and IGF-1 is the promotion of growth. GH and IGF-1 act very differently on glucose and lipid metabolism; GH blocks insulin action, promotes lipolysis and impedes lipogenesis, whereas IGF-1 has opposing effects.

Growth hormone (GH) signals through the GH receptor-associated tyrosine kinase JAK2. Growth hormone binding to its membrane-bound receptor enhances binding of JAK2 to the GHR, activates JAK2, and stimulates tyrosyl phosphorylation of both JAK2 and GHR. The activated JAK2/GHR complex recruits a variety of signaling proteins, thereby initiating multiple signaling pathways and cellular responses.

These proteins and transduction pathways include:
1) Stat transcription factors implicated in the expression of multiple genes, including the gene encoding insulin-like growth factor 1;
2) Shc adapter proteins that lead to activation of the grb2-SOS-Ras-Raf-MEK-ERK1,2 pathway;
3) Insulin receptor substrate proteins implicated in the phosphatidylinositol-3-kinase and Akt pathway;
4) Signal regulatory protein α, a transmembrane scaffold protein that recruits proteins including the tyrosine phosphatase SHP2;
5) SH2B1, a scaffold protein that can activate JAK2 and enhance GH regulation of the actin cytoskeleton.

Growth hormone is used to promote growth of short-statured children, and it's also used in the USA for the treatment of adult GH deficiency and for human immunodeficiency virus-associated wasting. Potential future uses of GH include suppression of chronic hypercatabolism, acceleration of healing in pediatric burn patients and treatment of some forms of infertility.

However, GH has also been linked to negative activities. In two large European studies, increased mortality was detected when critically ill patients with acute catabolism were placed on growth hormone therapy. In addition, growth hormone promotes insulin resistance and has been associated with retinal neovascularization and nephropathy, two debilitating complications of diabetes.

growth hormone/IGF-1 signaling transduction pathway

References

1. Carter-Su, C., Schwartz, J., & Argetsinger, L. S. (2016). Growth hormone signaling pathways. Growth Hormone & IGF Research, 28, 11-15.
2. Herrington, J., & Carter-Su, C. (2001). Signaling pathways activated by the growth hormone receptor. Trends in Endocrinology & Metabolism, 12(6), 252-257.
3. Junnila, R. K., List, E. O., Berryman, D. E., Murrey, J. W., & Kopchick, J. J. (2013). The GH/IGF-1 axis in ageing and longevity. Nature Reviews Endocrinology, 9(6), 366-376.