Growth hormone (GH), also known as somatotropin, is a protein hormone produced and secreted by the pituitary gland, a small endocrine gland located at the base of the brain. This substance plays a wide role in human development, impacting processes such as growth, cell reproduction, and tissue regeneration. Beyond childhood, GH continues to influence metabolism and maintain normal body structure throughout adulthood.
Unpacking the Growth Hormone Molecule
Growth hormone is a polypeptide chain, a protein of specific amino acids. The human growth hormone (hGH) consists of 191 amino acid residues. This linear sequence, known as the primary structure, dictates how the protein folds into its complex three-dimensional shape.
Approximately 45% of the hGH molecule is composed of alpha-helices. These helical segments are arranged in an “up-up-down-down” manner, forming a four-helix bundle that constitutes the protein’s core.
The intricate three-dimensional arrangement, or tertiary structure, of growth hormone is maintained by two internal disulfide bonds. These bonds form between sulfur atoms of cysteine amino acids, creating crucial links that stabilize the folded protein. This precise 3D structure is necessary for the hormone to carry out its biological functions.
How Structure Drives Function
Growth hormone’s three-dimensional shape enables its interaction with target cells. This shape allows GH to bind precisely to growth hormone receptors (GHRs) on cell surfaces, similar to a key fitting into a lock. This binding event triggers a series of conformational changes in the receptor, which initiates a cascade of intracellular signaling events.
Upon binding, GH causes GHRs to dimerize, activating an associated enzyme called Janus kinase 2 (JAK2). This activation leads to phosphorylation of tyrosine residues on both JAK2 and the GHR. These phosphorylated sites serve as docking points for other signaling molecules, such as STAT transcription factors.
Once activated, STAT transcription factors move into the cell’s nucleus, where they bind to DNA and regulate specific gene expression. This signaling pathway leads to various cellular responses, including increased protein synthesis, cell growth, and cell division. The precise structural interaction between GH and its receptor is responsible for its widespread physiological effects, influencing skeletal growth, muscle mass, bone density, and overall metabolism.
When Growth Hormone Structure Goes Awry
When growth hormone’s finely tuned structure is compromised, or its production levels are imbalanced, health consequences can arise. Genetic mutations can lead to abnormally structured GH that may not bind effectively to its receptors, or affect the growth hormone receptor itself, leading to growth hormone insensitivity. Such defects can result in impaired growth and metabolic issues.
An overproduction of growth hormone, often due to a benign pituitary tumor, can lead to excessive growth. If this occurs during childhood, before bone growth plates have fused, it results in gigantism, characterized by unusually tall stature and enlarged hands and feet. If excess GH production happens in adulthood, after growth plates have fused, it leads to acromegaly, causing enlargement of bones and tissues, particularly in the face, hands, and feet, without an increase in height.
Conversely, a deficiency in growth hormone production, or a structural defect rendering the hormone inactive, can lead to stunted growth. Dwarfism, characterized by shorter stature, can be caused by genetic conditions that affect bone growth and development, including those that disrupt growth hormone action. Maintaining the correct structure and appropriate levels of growth hormone is important for proper bodily function and development.