03c-GrowthHormone-2

Regulation of Growth Hormone

  • Hypothalamus Role

    • Growth hormone release is regulated by the hypothalamus.

    • Cells in the hypothalamus produce peptide hormones that are released into a capillary bed and travel through a portal system to the anterior pituitary.

  • Anterior Pituitary Function

    • In the anterior pituitary, peptide hormones act on somatotropes to stimulate growth hormone production.

  • Regulatory Mechanisms

    • Positive Regulator:

      • Growth Hormone Releasing Hormone (GHRH) from the arcuate nucleus stimulates adenylyl cyclase activity, increasing cAMP levels and promoting growth hormone release.

    • Negative Regulator:

      • Growth Hormone Release Inhibiting Hormone (somatostatin) from the periventricular nucleus inhibits adenyl cyclase, decreasing cAMP and blocking growth hormone release.

    • Both GHRH and somatostatin are essential for proper regulation.

    • A decrease in somatostatin leads to increased growth hormone release, but GHRH must also be present.

Effects of Growth Hormone

  • Insulin-like Growth Factors (IGFs)

    • Growth hormone stimulates the liver to secrete IGF-1 and IGF-2.

    • IGF-2 is crucial for fetal development, while IGF-1 mediates growth hormone's effects on:

      • Cartilage formation and bone growth

      • Protein synthesis

      • Muscle mass increase

      • Fat cell regulation

Pathological Conditions

  • Gigantism

    • Results from excessive growth hormone before puberty, causing elongation of long bones.

    • Individuals may grow up to 2 meters (8 feet) tall.

  • Acromegaly

    • Caused by growth hormone overproduction after puberty, leading to increased bone and cartilage growth but no height increase due to fused epiphyseal plates.

    • Symptoms include enlarged nose, ears, jaw, and internal organs.

    • Patients often experience a shortened lifespan.

Regulation Issues and Treatment

  • Increased Growth Hormone Causes

    • Hypothalamus: Low somatostatin or high GHRH

    • Pituitary: Pituitary tumors (e.g., adenomas)

    • Liver: Increased growth hormone receptors leading to excess IGF production

  • Treatment Approaches

    • Pituitary tumor removal for acromegaly.

    • Administration of IGF antagonists if IGF levels are elevated due to liver receptor issues.

Growth Hormone Deficiency

  • Symptoms in Children

    • Short stature, decreased muscle mass, increased adipose tissue

    • Low IGF levels associated with low growth hormone levels.

  • Diagnosis

    • Blood tests for growth hormone and IGF levels due to pulsatile nature of growth hormone release.

    • Testing can vary based on circadian rhythms.

  • Treatment Options

    • Synthetic growth hormone for low levels.

    • IGF administration if low IGF levels are the issue.

Ethical Considerations

  • Growth hormone therapy more common in boys than girls due to societal biases.

  • Debate on administering treatment to children within normal height ranges.

  • Risks of excessive growth hormone leading to conditions like gigantism and acromegaly.

Dwarfism Examples

  • Lehrone Syndrome

    • Autosomal recessive disorder with normal/high growth hormone but low IGF due to receptor issues at the liver.

    • Characterized by short stature, underdeveloped mandible, and truncal obesity.

  • Hypopituitary Dwarfism

    • Pituitary underdevelopment leads to low growth hormone and IGF levels.

  • Pygmy Dwarfism

    • Normal growth hormone levels but low IGF levels due to carrier protein issues. Proportional body build.

  • Nutrition Considerations

    • Rule out malnutrition when diagnosing dwarfism.

Combined Hormone Treatments

  • Growth hormone and thyroid hormone treatments are synergistic for growth enhancement, particularly in hypothyroid children.

  • Thyroid hormone increases growth hormone receptor sensitivity and promotes growth hormone efficacy.

Summation of Hormonal Interactions

  • Hormones can act permissively; the presence of one hormone enhances the effect of another.

  • Thyroid hormone acts to increase responses to epinephrine by increasing receptor numbers.

Conclusion

  • Overview of growth hormone regulation, effects of excess and deficiency, ethical considerations, and treatment options.

  • Next topics will shift focus to thyroid hormone regulation, synthesis, and mechanisms.