Growth Hormone Functions and Effects

Growth Hormone (GH)

• GH has diverse effects, including sodium retention, decreased insulin sensitivity, lipolysis (fat breakdown), protein synthesis (anabolic), bone growth stimulation, and IGF-1 secretion stimulation.
• GH and insulin both promote protein synthesis, making them anabolic hormones. Insulin also promotes triglyceride and glycogen synthesis, unlike GH.
• IGF-1 has insulin-like activity, anti-lipolytic activity, and promotes protein synthesis.
• GH's direct actions stimulate protein synthesis. Indirectly, it promotes protein synthesis via IGF-1 and stimulates bone growth. It also increases muscle protein synthesis, liver glucose production and gluconeogenesis, decreases insulin action on glucose uptake, and increases the action of lipolytic agents (epinephrine and glucagon). This leads to increased free fatty acid and ketone levels.
• Factors stimulating GH secretion include hypoglycemia, stress, exercise, protein meals (amino acids like arginine), sleep onset, androgens, and estrogens.
• GH levels are highest during adolescence and lower in adulthood and old age.
• Low GH leads to reduced lean body mass, smaller protein mass, and reduced bone mass.
• Factors inhibiting GH include free fatty acids, cortisol, glucose, REM sleep, and IGF-1.
• In a 16-year-old boy, GH simultaneously increases protein synthesis and glucose production.

Catabolic Hormones

• Catabolic hormones (glucagon, epinephrine, and cortisol) have a clear catabolic function.

Glucagon

• Secreted by alpha cells in the pancreas in response to low blood glucose (e.g., fasting).
• Actions:
  • Liver: stimulates gluconeogenesis (glucose synthesis from amino acids) and glycogenolysis (glycogen breakdown).
  • Fat tissue: stimulates lipolysis (triglyceride breakdown).
• Glucagon synthesis starts with a large precursor, then undergoes post-translational processing. The products—glucagon, MPGF, GPRP, GRPP—vary based on the cells and enzymes involved. Intestine cells produce GLP-1 and other molecules.
• Summary of Glucagon Actions:
  • Stimulates liver glycogenolysis (not muscle).
  • Stimulates glucose synthesis through gluconeogenesis.
  • Stimulates lipolysis.
  • Generates ketones.
  • Mobilizes energy stores.
• Glucagon increases glucose output through various mechanisms including the activation of protein kinase A, glycogen breakdown, and inhibition of glucose metabolism.
• Glucagon increases lipolysis via hormone-sensitive lipase activation, enhancing triglyceride breakdown to glycerol and free fatty acids.
• Factors stimulating glucagon secretion include amino acids, GI hormones (CCK, gastrin), cortisol, exercise, infection, and fasting.
• Factors inhibiting glucagon secretion include glucose, free fatty acids, ketones, secretin, insulin, somatostatin, and alpha/beta-adrenergic stimulation

Epinephrine

• Produced by the adrenal medulla.
• Actions:
  • Glycogenolysis: breaks down glycogen in liver and muscle.
  • Stimulates gluconeogenesis.
  • Decreases glucose uptake.
  • Stimulates lipolysis (via hormone-sensitive lipase).
  • Stimulates ketogenesis.
  • Mobilizes energy stores.
• Factors stimulating epinephrine release include anxiety, fear, pain, hypoglycemia, hypotension, hypovolemia, hypothermia, hypoxia, and exercise.
• Epinephrine's effects vary by receptor type. This means a single receptor can have a different impact on different tissues.

Cortisol

• Factors Stimulating Cortisol Secretion: Pain, low glucose, low blood pressure, low volume, low temperature, low oxygen, exercise
• Actions:
  • Liver: Enhances norepinephrine and glucagon actions on gluconeogenesis for more glucose production.
  • Adipose Tissue: Promotes lipolysis.
  • Skeletal Muscle: Facilitates protein breakdown and glycogenolysis.
• Cortisol, a glucocorticoid, inhibits calcium uptake in the GI tract, bone formation, collagen synthesis, and IGF-1's actions on bone and muscle.
• It aids in fetal organ maturation (liver, lungs, GI tract).
• Glucocorticoid net effects: inhibit growth, decrease stature in children, increase osteoporosis and muscle atrophy in adults.

Combined Catabolic Effects (Glucagon, Epinephrine, Cortisol) During Fasting

• Hypoglycemia triggers glucagon and epinephrine release.
• Glucagon and epinephrine stimulate gluconeogenesis and glycogenolysis to increase glucose production.
• Cortisol enhances glucagon and epinephrine's effects by producing enzymes. Cortisol's effects are slower due to its steroid nature. Cortisol also increases liver glycogen storage, breaks down skeletal muscle protein, and has a longer-term effect.

Disease States (Cortisol Imbalance)

• Cortisol Excess (Cushing's Syndrome): Hyperglycemia, insulin resistance, protein wasting, poor wound healing, truncal obesity, hypertension, hypernatremia, hypokalemia, infections, decreased inflammatory responses, euphoria.
• Cortisol Deficiency (Addison's Disease): Hypoglycemia, low blood pressure, poor response to angiotensin II, low volume, low sodium, high potassium, depression, skin hyperpigmentation.

Hormonal Changes in Different Metabolic States

• Summarizes hormonal changes like glucose, insulin, glucagon, epinephrine, GH, and cortisol during fed, fasting, extended fasting, and starvation states. Highlights the net effects of each state (e.g., fed = absorption/storage, fasting = fuel mobilization).