Growth Hormone Regulation

Growth Hormone (GH/Somatotropin)

• GH regulates overall body growth via the hypothalamic-pituitary axis.
• The hypothalamus releases Growth Hormone-Releasing Hormone (GHRH), which binds to somatotroph cells in the anterior pituitary, stimulating GH secretion.
• Stimuli for release include hypoglycemia, epinephrine, estrogen, and testosterone.
• Release is inhibited by increased GH, somatomedins (IGF-1), and somatostatin (GHIH).
• GH and IGF-1 inhibit GHRH and increase somatostatin through a negative feedback loop.
• Direct effects involve stimulating lipolysis in adipose tissue and that increases energy.
• Direct effects involve triggering gluconeogenesis and glycogenolysis in the liver, leading to increased blood glucose.
• Direct effects include increasing insulin resistance in tissues.
• Indirect effects via IGF-1 include stimulating amino acid uptake, protein synthesis, and growth in muscles.
• Indirect effects via IGF-1 include stimulating osteoblasts and chondrocytes for bone growth.

Antidiuretic Hormone (ADH/Vasopressin)

• Produced in the paraventricular and supraoptic nuclei of the hypothalamus and stored/released from the posterior pituitary.
• Increased blood osmolarity, detected by osmoreceptors, is a stimulus for release.
• Low blood pressure, detected by baroreceptors in the carotid artery and aorta, is a stimulus for release.
• Acts on the distal convoluted tubule and collecting ducts of the kidneys.
• Binds to AVPR2 receptors, inserting aquaporin-2 water channels, increasing water reabsorption and reducing urine output.
• Causes vasoconstriction, increasing blood pressure.
• Increased blood pressure inhibits the hypothalamus through baroreceptors, which decreases ADH secretion via negative feedback.

Insulin

• Produced by Beta cells in the Islets of Langerhans in the pancreas.
• Release is stimulated by high blood glucose, glucagon, cortisol, and acetylcholine.
• Release is inhibited by norepinephrine and somatostatin.
• In the liver, it converts glucose to glycogen and inhibits gluconeogenesis.
• In adipose tissue, it converts fatty acids to fat.
• In skeletal muscle, it increases amino acid uptake, protein synthesis, and muscle growth.
• Increased glucose uptake lowers blood glucose, reducing insulin secretion via negative feedback.

Glucagon

• Produced by Alpha cells in the Islets of Langerhans in the pancreas.
• Release is stimulated by low blood glucose, adrenaline, and cholecystokinin.
• Release is inhibited by high blood glucose, insulin, and somatostatin.
• Converts glycogen to glucose (glycogenolysis) and stimulates gluconeogenesis in the liver.
• Stimulates lipolysis (fat breakdown) in adipose tissue.
• Is secreted during fasting.
• After a meal, high glucose levels lead to insulin release, which inhibits glucagon.

Cortisol (Glucocorticoid)

• Produced by the Zona Fasciculata of the Adrenal Cortex.
• The hypothalamus releases CRH, stimulating ACTH release from the anterior pituitary, which then stimulates cortisol production.
• Release is stimulated by stress, hypoglycemia, infection, and sleep deprivation.
• Cortisol inhibits CRH and ACTH production via negative feedback.
• Suppresses inflammation and inhibits IL-2 production in the immune system.
• Stimulates gluconeogenesis and glycogen storage in the liver.
• Stimulates proteolysis, increasing amino acids for gluconeogenesis in muscles.
• Stimulates lipolysis in adipose tissue.
• Increases vasoconstriction, raising blood pressure in blood vessels.
• Inhibits osteoblasts, reducing bone formation in bone.

Thyroid Hormones (T3 & T4)

• Produced by Follicular Cells of the Thyroid Gland.
• The hypothalamus releases TRH, stimulating TSH release from the anterior pituitary, which then stimulates T3 and T4 production.
• High T3/T4 inhibits TRH and TSH production via negative feedback.
• Increases Na+/K+ ATPase activity in all cells, which increases metabolic rate.
• Increases gluconeogenesis and lipolysis in the liver.
• Increases heart rate and cardiac output in the cardiovascular system.
• Essential for CNS development and bone growth.

Parathyroid Hormone (PTH)

• Produced by Chief Cells of the Parathyroid Glands.
• Release is stimulated by low extracellular calcium levels.
• Release is inhibited by high extracellular calcium levels.
• Stimulates osteoblasts to release cytokines, activating osteoclasts and increasing calcium release in bone.
• Inhibits phosphate reabsorption in the proximal tubule, lowering serum phosphate in the kidneys.
• Increases calcium reabsorption in the distal tubule of the Kidneys.
• Activates 1-alpha-hydroxylase, which converts vitamin D into its active form (calcitriol), increasing calcium absorption in the intestines.

Hormonal Feedback Loops

• T3/T4 Inhibit TRH & TSH secretion (negative feedback).
• Cortisol inhibits CRH & ACTH secretion (negative feedback).
• Increased glucose inhibits glucagon release (negative feedback).
• PTH is inhibited by high calcium levels (negative feedback).
• Oxytocin stimulates uterine contractions, leading to further oxytocin release during childbirth (positive feedback).