Growth hormone receptor

By Jennifer McDowall

To view GH receptor structure

How tall you grow depends upon many different gene products, but one in particular, the growth hormone (GH), is a key factor. GH acts to increase lean body mass, stimulating the growth and metabolism of muscle, bone and cartilage cells, while reducing body fat. The pattern of GH secretion into the bloodstream is important in determining the rate of body growth, so it is not surprising that this molecule is highly regulated. The level of GH varies in different tissues, at different times of the day, at different ages, and in different sexes. GH is able to effect many cellular processes other than growth. At the cellular level, GH acts to regulate cell growth, differentiation, apoptosis, and reorganisation of the cytoskeleton, affecting such diverse processes such as cardiac function, immune function, brain function, and aging. GH can also affect metabolism, showing insulin-like effects such as stimulating amino acid transport, protein synthesis, glucose transport, and lipogenesis. GH is able to exert its pleiotropic effects through the GH receptor (GHR), which can stimulate many diverse signalling pathways leading to different cellular responses.

Growth failure can be caused by a deficiency in growth hormone action, which can arise due to a dysfunction of the GHR. Laron-type pituitary dwarfism (Laron syndrome) [MIM:262500] is associated with dysfunctional GHR, which results in a failure to generate IGF1 (insulin-like growth factor 1) in response to GH, even though circulating levels of GH are normal; IGH1 and its receptor (IGF1R) are required to activate the signal transduction pathway leading to growth. Laron Syndrome patients display short stature, delayed bone age and hip degeneration, and are insensitive to treatment with exogenous GH.

“Early to bed and early to rise, Makes a man healthy, wealthy and wise”

There is some truth to this fifteenth century nursery rhyme. Research has shown that lack of sleep in children can cause reduced growth, as well as learning and cognitive deficits. Levels of growth hormone are found to increase when we are asleep, reaching a peak during the first few hours. Various hormones help to regulate both sleep patterns and growth hormone levels during sleep. Growth hormone-releasing hormone (GHRH) promotes non-REMS sleep, while the ligand for the growth hormone secretagogue receptor, ghrelin, promotes slow-wave sleep, both acting as sleep regulatory factors. Ghrelin itself increases during the early part of the night, promoting sleep-associated growth hormone secretion, which reaches a peak during the night. Sleep deprivation acts to suppress the nocturnal increase in ghrelin, and nearly abolishes the high amplitude pulses in growth hormone levels. Other hormones, such as corticotropin-releasing hormone (CRH), act to impair sleep, and changes in the ratio of GHRH to CRH can affect hormonal activity. It is thought that the increase in CRH associated with aging and depression may contribute to sleep aberrations and blunted growth hormone levels.

Next: Growth hormone receptor signalling, unlocking a regulatory network