Growth Hormone (GH)

1. Overview

Growth Hormone (GH), also called somatotropin, is a peptide hormone that plays a fundamental role in stimulating growth, cell reproduction, and regeneration. It is essential during childhood and adolescence for normal physical development and continues to influence metabolism in adults. GH acts both directly on tissues and indirectly through insulin-like growth factor 1 (IGF-1), which is produced mainly in the liver.

2. Location

GH is synthesized and secreted by the somatotroph cells of the anterior pituitary gland (pars distalis). Its release is regulated by the hypothalamus through two key hormones:

• Growth Hormone-Releasing Hormone (GHRH): Stimulates GH secretion.

• Somatostatin (Growth Hormone-Inhibiting Hormone): Inhibits GH secretion.

GH secretion follows a pulsatile pattern and is influenced by factors such as sleep, exercise, stress, hypoglycemia, and nutritional status.

3. Structure

GH is a single-chain polypeptide hormone composed of 191 amino acids, with a molecular weight of approximately 22 kDa. It is encoded by the GH1 gene on chromosome 17. GH is water-soluble and acts through membrane-bound receptors, primarily the growth hormone receptor (GHR), which activates the JAK-STAT signaling pathway upon ligand binding.

4. Function

GH has widespread anabolic and metabolic functions:

• Promotes linear growth by stimulating chondrocyte proliferation in the epiphyseal growth plates of bones.

• Stimulates production of IGF-1 in the liver and peripheral tissues, which mediates many of GH’s growth-promoting effects.

• Increases protein synthesis and muscle mass by enhancing amino acid uptake and ribosomal activity.

• Mobilizes fat by stimulating lipolysis in adipose tissue, leading to increased free fatty acids in circulation.

• Reduces carbohydrate utilization by antagonizing insulin, leading to increased blood glucose levels.

5. Physiological role(s)

GH is vital throughout life for growth, metabolism, and tissue maintenance:

• Childhood and adolescence: Drives linear skeletal growth and organ development.

• Adulthood: Maintains muscle mass, bone density, and regulates body composition and lipid metabolism.

• Metabolic adaptation: In fasting or stress conditions, GH promotes fat breakdown and conserves glucose for vital organs.

• Tissue repair: Supports cellular regeneration and healing processes in various tissues.

• Neuroprotective effects: GH and IGF-1 may support brain development and cognitive function.

6. Clinical Significance

Disorders involving GH can have significant effects on development and metabolism:

• Growth Hormone Deficiency (GHD):

  • In children: Causes short stature, delayed growth, and delayed puberty.

  • In adults: Leads to increased fat mass, decreased muscle and bone mass, reduced quality of life, and cardiovascular risk.

  • Causes may include pituitary tumors, trauma, genetic mutations, or idiopathic origins.

  • Treated with recombinant human GH injections.

• Excess Growth Hormone:

  • Gigantism: Occurs when GH excess happens before epiphyseal plate closure in children, leading to abnormal height and growth.

  • Acromegaly: Occurs in adults after growth plate fusion, leading to enlarged hands, feet, facial features, and organomegaly. Commonly caused by a GH-secreting pituitary adenoma.

  • Symptoms may include headache, joint pain, insulin resistance, and sleep apnea.

  • Treatment includes surgical removal of pituitary tumors, somatostatin analogs, GH receptor antagonists, or radiation therapy.

• GH misuse in athletics:

  • Illicit use of GH for performance enhancement or anti-aging is prohibited and carries risks such as insulin resistance, carpal tunnel syndrome, and abnormal tissue growth.

• GH in aging and metabolic health:

  • GH levels decline with age, and low levels are associated with increased fat mass and reduced lean body mass. However, GH therapy for aging remains controversial and is not widely recommended.