Summary
Highlights
Growth hormone-releasing hormone (GHRH) is secreted from the arcuate nucleus of the hypothalamus, circulates through the hypophyseal portal system, and stimulates somatotropes in the anterior pituitary (adeno-hypophysis) to release growth hormone (GH).
Stimuli for GHRH and subsequent GH release include high amino acid levels, low glucose (hypoglycemia), low fatty acid levels (hypolipidemia), exercise, and healthy stressors. These factors activate the arcuate nucleus in the hypothalamus.
A portion of released growth hormone travels to the liver and binds to tyrosine kinase-like receptors, activating the JAK-STAT pathway. This pathway phosphorylates STAT (Signal Transducer Activator of Transcription), leading to gene transcription and the production of Insulin-Like Growth Factor Type 1 (IGF-1).
IGF-1 promotes protein synthesis in muscle cells by binding to receptors, activating signaling pathways that increase amino acid uptake and protein production. This leads to increased muscle size and function (hypertrophy).
IGF-1 regulates bone activity by increasing both osteoblastic (bone deposition) and osteoclastic (bone resorption) activity, playing a crucial role in bone growth, particularly endochondral ossification. It also stimulates the synthesis of type 1 collagen and proteoglycans, enhancing bone density.
At the epiphyseal plates of bones, IGF-1 stimulates chondrocyte differentiation, size increase, and proliferation. This process, known as interstitial growth, leads to the elongation of bones by converting cartilage into bone tissue.
Growth hormone directly affects the liver to promote gluconeogenesis, increasing blood glucose levels by converting non-carbohydrate sources like glycerol into glucose. It also acts on adipose tissue to stimulate lipolysis, breaking down triglycerides into glycerol and fatty acids, making glycerol available for gluconeogenesis. Growth hormone can also directly increase amino acid uptake in muscle cells.
IGF-1 primarily affects muscles (increased amino acid uptake, protein synthesis, muscle growth), bones (increased osteoblastic/osteoclastic activity, collagen type 1, proteoglycans, endochondral ossification), and cartilage (increased chondroblast proliferation, size, differentiation, leading to interstitial bone growth and increased bone length).
Growth hormone directly impacts the liver to increase gluconeogenesis and IGF-1 production. It also acts on adipose tissue to enhance lipolysis and on muscle tissue to increase amino acid uptake.