Growth Hormone (GH/Somatotropin)

Growth Hormone (GH/Somatotropin)

• Body growth is regulated via the hypothalamic-pituitary axis.
• The release of Growth Hormone (GH) occurs as follows: The hypothalamus releases Growth Hormone-Releasing Hormone (GHRH) which then binds to somatotroph cells in anterior pituitary, resulting in GH secretion.

Control of GH Release

• GH release is stimulated by hypoglycemia, epinephrine, estrogen, and testosterone.
• GH 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.

Effects of GH

• Direct effects of GH includes stimulating lipolysis in adipose tissue for energy.
• The Liver is triggered by GH to undergo gluconeogenesis and glycogenolysis, which then increases blood glucose.
• GH increases insulin resistance in tissues.
• Indirect effects via IGF-1 in muscles stimulates amino acid uptake, protein synthesis, and growth.
• Indirect effects via IGF-1 in bones stimulates osteoblasts and chondrocytes, which then leads to bone growth.

Antidiuretic Hormone (ADH/Vasopressin)

• ADH is produced in the paraventricular and supraoptic nuclei of the hypothalamus.
• ADH is stored and released from the posterior pituitary.

Stimuli for Release of ADH

• Increased blood osmolarity detected by osmoreceptors stimulates ADH release.
• Low blood pressure detected by baroreceptors in the carotid artery and aorta also stimulates ADH release.

Target Cells & Effects of ADH

• ADH acts on the distal convoluted tubule & collecting ducts in the kidneys.
• ADH binds AVPR2 receptors, thereby inserting aquaporin-2 water channels, increasing water reabsorption, and reducing urine output.
• In blood vessels, ADH causes vasoconstriction, resulting in increased blood pressure.

Negative Feedback Loop of ADH

• Increased blood pressure causes baroreceptors to inhibit the hypothalamus, decreasing ADH secretion.

Insulin

• Insulin is produced by Beta cells in the Islets of Langerhans in the pancreas.
• Insulin release is stimulated by high blood glucose, glucagon, cortisol, and acetylcholine.
• Insulin release is inhibited by norepinephrine and somatostatin.

Target Organs & Effects of Insulin

• The liver converts glucose to glycogen, which inhibits gluconeogenesis.
• Adipose tissue converts fatty acids to fat when stimulated by insulin.
• Skeletal muscle increases amino acid uptake, protein synthesis, and muscle growth when stimulated by insulin.

Negative Feedback of Insulin

• Increased glucose uptake lowers blood glucose, which then reduces insulin secretion.

Glucagon

• Glucagon is produced by Alpha cells in the Islets of Langerhans in the pancreas.
• Glucagon release is stimulated by low blood glucose, adrenaline, and cholecystokinin.
• Glucagon release is inhibited by high blood glucose, insulin, and somatostatin.

Target Organs & Effects of Glucagon

• The liver converts glycogen to glucose (glycogenolysis) and also stimulates gluconeogenesis when stimulated by glucagon.
• Adipose tissue stimulates lipolysis (fat breakdown) when stimulated by glucagon.

Interplay with Insulin and Glucagon

• During fasting, glucagon is secreted.
• After a meal, high glucose leads to insulin release, which then inhibits glucagon.

Cortisol (Glucocorticoid)

• Cortisol is produced by the Zona Fasciculata of the Adrenal Cortex.
• The hypothalamus releases CRH, which stimulates ACTH release from the anterior pituitary, which stimulates cortisol production.
• Cortisol release is stimulated by stress, hypoglycemia, infection, and sleep deprivation.
• Cortisol inhibits CRH and ACTH production through negative feedback.

Target Organs & Effects of Cortisol

• In the immune system, cortisol suppresses inflammation, inhibits IL-2 production.
• In the liver, cortisol stimulates gluconeogenesis and glycogen storage.
• In muscles, cortisol stimulates proteolysis, which increases amino acids for gluconeogenesis.
• In adipose tissue, cortisol stimulates lipolysis.
• In blood vessels, cortisol increases vasoconstriction, raising blood pressure.
• In bone, cortisol inhibits osteoblasts, which reduces bone formation.

Thyroid Hormones (T3 & T4)

• T3 & T4 hormones are produced by Follicular Cells of the Thyroid Gland.
• The hypothalamus releases TRH which then stimulates TSH release from the anterior pituitary, which then stimulates T3 and T4 production.
• High T3/T4 inhibits TRH & TSH production through negative feedback.

Target Organs & Effects of T3 & T4

• In all cells, T3 & T4 increases Na+/K+ ATPase activity, which increases metabolic rate.
• In the liver, T3 & T4 increases gluconeogenesis and lipolysis.
• In the cardiovascular system, T3 & T4 increases heart rate and cardiac output.
• T3 & T4 are essential for CNS development and bone growth.

Parathyroid Hormone (PTH)

• PTH is produced by Chief Cells of the Parathyroid Glands.
• PTH release is stimulated by low extracellular calcium and inhibited by high extracellular calcium.

Target Organs & Effects of PTH

• In bone, PTH stimulates osteoblasts to release cytokines to activate osteoclasts, which then increases calcium release.
• In the kidneys for the proximal tubule, PTH inhibits phosphate reabsorption, which then lowers serum phosphate.
• In the kidneys for the distal tubule, PTH increases calcium reabsorption and activates 1-alpha-hydroxylase enzyme to convert vitamin D into active form (calcitriol), which then increases calcium absorption in intestines.

Hormonal Feedback Loops

Negative Feedback Loops

• T3/T4 inhibit TRH & TSH secretion through negative feedback.
• Cortisol inhibits CRH & ACTH secretion through negative feedback.
• Increased glucose inhibits glucagon release through negative feedback.
• PTH is inhibited by high calcium levels through negative feedback.

Positive Feedback Loop

• Oxytocin stimulates uterine contractions, leading to further oxytocin release during childbirth in a positive feedback loop.