The intracellular signaling activation that occurs, as stated above, also has a significant impact on the basal metabolic functions of organ tissues. HGH impacts metabolism primarily by up-regulating the production of insulin-like growth factor-1 and its subsequent effect on peripheral cells. The net result is to encourage the growth of tissue and to create a hyperglycemic environment in the body. Furthermore, it acts to inhibit apoptosis of the cell, thus prolonging the lifespan of existing cells. Insulin-like growth factor-1 binds to its receptor, IGF-1R, on the cellular surface and activates a tyrosine kinase-mediated intracellular signaling pathway that phosphorylates various proteins intracellularly leading to increased metabolism, anabolism, and cellular replication and division. Activation of this phosphorylation intracellular signaling cascade results in a cascade of protein activation, which leads to increased gene transcription of the affected cells and ultimately causes increased gene replication and cellular growth. Chondrocytes and osteoblasts receive signals to increase replication and thus allow for growth in size via HGH’s activation of the mitogen-activated protein (MAP) kinases designated ERKs (extracellular signal-regulated kinases) 1 and 2 cellular signaling pathways. However, it is most notorious for its growth-promoting effect on cartilage and bone, especially in the adolescent years. HGH induces growth in nearly every tissue and organ in the body. One can think of the effects of HGH as a combined effect of both HGH and insulin-like growth factor-1. Insulin-like growth factor-1 then has an impact on the growth and metabolism of peripheral tissues. Once activated, the Janus activating tyrosine kinases (JAKs) 1 and 2 will bind to the latent cytoplasmic transcriptions factors STAT1, STAT3, and STAT5, and be transported into the nucleus inducing increased gene transcription and metabolism to produce insulin-like growth factor-1 for release into the circulation. The indirect effects occur primarily by the action of insulin-like growth factor-1, which hepatocytes primarily secrete in response to elevated HGH binding to surface receptors.
The direct effects of HGH on the body are through its action on binding to target cells to stimulate a response. HGH has two mechanisms of effect: direct action and indirect action. In general, HGH levels will be increased in childhood, spike to their highest levels during puberty, and subsequently decrease with increased age. The net effect of this regulatory mechanism produces a pulsatile release of HGH into circulation that varies hourly.
Additionally, HGH will negatively feedback into the hypothalamus, thus decreasing GHRH production. When elevated, ghrelin binds to somatotrophs to stimulate HGH secretion. Insulin-like growth factor-1 also acts to inhibit HGH by both directly inhibiting somatotrophic HGH release and indirectly through synergistically increasing the release of somatostatin. Functionally, the ghrelin response is protective against hypoglycemia. Ghrelin is a hormone produced by the stomach as part of the hunger response. Somatostatin inhibits the release of GHRH as well as the HGH release response to GHRH stimulus and increases in hypoglycemia. GHRH functions to promote HGH production and release. The primary regulation factors are growth hormone-releasing hormone (GHRH) produced in the hypothalamus, somatostatin, produced in various tissues throughout the body, and ghrelin, which is produced in the gastrointestinal tract. Its production is tightly regulated through several complex feedback mechanisms in response to stress, exercise, nutrition, sleep, and growth hormone itself. Human growth hormone is produced via the anterior pituitary of the brain in the acidophilic, somatotrophic cells.
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