By Dillon Lim - Medicine Student @ Brasenose College, Oxford
Growth Hormone (GH) is one of many protein hormones produced in the pituitary gland of the brain. As with many other pituitary hormones, GH is released under control of another hormone produced in the hypothalamus – Growth Hormone Releasing Hormone (GHRH). GHRH travels down in a special portal blood system to trigger GH release. GHRH itself is released in stress, in exercise and in slow-wave (deep) sleep – these last two are reasons why we encourage children to get as much uninterrupted sleep and physical activity as possible!
After its release, GH travels in the blood – mostly free in solution, but with some bound to binding proteins. Unlike many hormones which have a more specific target tissue and effect, GH has a more diverse action. Generally, it supports anabolism, or metabolic pathways which build up biomolecules. It acts on the liver to increase de novo glucose production (a process called gluconeogenesis) and insulin production. This has the effect of maintaining/raising blood glucose. At adipose tissue (our body’s fat stores), GH stimulates lipolysis, increasing available energy that can be used for anabolic activity. GH acts on nerves, muscle, the vasculature, and skeletal and cartilaginous structures, among others, to increase differentiation and proliferation.
At several places (but most importantly the liver), GH triggers production of IGF-1, a protein that looks a lot like insulin but behaves more like GH, and helps to mediate many of its effects.
The GH receptor (GHR) belongs to a family called the receptor Tyrosine kinases, or RTKs. The binding of GH results in domains of the receptor phosphorylating each other. This triggers intracellular cascades of phosphorylation, that lead to changes in transcriptional and metabolic activity.
Several diseases are associated with problems with GH release. In hyperproduction of GH (sometimes as a result of a tumour in the pituitary gland), children develop a condition called gigantism while adults develop acromegaly. The reason for the difference is that parts of our long bones fuse together in puberty – so while all bones grow excessively in children with excess GH, in adults, growth only takes place at a few places – most notably in the face. In hypoproduction, we see a condition called pituitary dwarfism – proportionally short stature, with increased adiposity. It is also possible to have insensitivity to GH as a result of a mutated GHR – what we call Laron syndrome. These individuals are usually between 4 – 10 standard deviations below the mean height.
Because of GH’s effects on glucose metabolism, 25% of acromegaly patients go on to develop diabetes mellitus. Equally, the treatment of pituitary dwarfism with supplementary GH needs to be very carefully managed – previous doses increased the incidence of diabetes in children receiving the treatment by six times.
Given GH’s links with growth and proliferation, it’s perhaps not surprising that there are associations between GH levels and cancer. Girls in the top 20% of their height cohort have a higher risk for breast cancer, and height tends to be a stronger predictor of breast cancer than other traditional factors such as BMI, and age of first period. Acromegaly patients have a marked increase in cancer incidence, while pituitary dwarfism patients have disproportionately low incidences.
Growth Hormone (Somatotropin). http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/gh.html
Normal Physiology of Growth Hormone in Adults. https://www.ncbi.nlm.nih.gov/books/NBK279056/
Growth Hormone. https://www.ncbi.nlm.nih.gov/books/NBK482141/
NORD has information on the three conditions mentioned in its Rare Disease Database. https://rarediseases.org/for-patients-and-families/information-resources/rare-disease-information/