endocrine control of growth

• Endocrine control of growth


  The organized addition of new tissue that occurs normally in development
• With the exception of longitudinal growth, many of the processes involved continue to operate throughout life (e.g. tissue remodeling)
• Factors influencing growth


  • Genetics
  • Nutrition
  • Growth influencing hormones - growth hormone, thyroid hormone, somatomedins/IGFs, insulin, sex hormones
  • Chronic stress and disease
• Growth Hormone


  Polypeptide hormone produced in somatotrophs of anterior pituitary, secretion regulated by GHRH and GHIH (somatostatin), transported bound to growth hormone binding protein, targets many tissues where it influences fuel metabolism, GH binding to enzyme-linked receptor produces activation of kinase cascade which ultimately alters gene transcription, overall effect is to use up fat stores and promote protein synthesis
• Growth hormone secretion pattern


  • Irregular pulses, largest bursts during deep sleep, pulse amplitude maximum at puberty, then declines

  
• Regulation of the Anterior Pituitary


  1. Hypothalamus

  2. TSH

  3. ACTH

  4. Growth hormone

  5. Liver

  6. Somatomedins

  7. Many tissues

  
• Factors influencing GH secretion


  • Secretion is stimulated by: GH-releasing hormone (GHRH), oestrogens & androgens, ¯blood glucose, ¯blood fatty acids, exercise, excitement / stress / trauma, sleep

  Secretion is inhibited by: GH-inhibiting hormone (GHIH; somatostatin), somatomedins (-ve feedback), obesity, ­blood glucose, ­blood fatty acids, aging

  
• Somatomedins (Insulin-like growth factors)


  Peptide hormones that have strong mitogenic properties (encourage cell division), produced primarily in the liver, but also in most other tissues (where it has an autocrine / paracrine effect), IGF-1 effects most cells in the body where it stimulates cell growth, multiplication and inhibits apoptosis (programmed cell death), IGF-2 is a growth promoting hormone during gestation

  
• Bone Growth


  Growth Hormone (via IGF-1): stimulates proliferation of epiphyseal cartilage, increases conversion of cartilage to new bone (increasing length of long bones & skeleton until epiphyses of long bones fuse with shafts), ­proliferation of periosteal osteoblasts (increasing bone thickness), ­bone remodeling
• Hormones influencing growth


  • Thyroid hormones: Permissive for GH synthesis, release (via ↑GHRH receptor) & actions (↑GH receptor, ↑IGF-I, ↑IGF-I receptor)

  Insulin: Required for optimal effects of growth hormone (IGF-I is low in diabetes)

  Gonadal hormones: During puberty estrogens increase GH pulse amplitude & frequency; also play a role in closure of epiphyseal plates – terminating growth IN BOTH SEXES. Androgens involved in the pubertal growth spurt by stimulating protein synthesis (increase muscle mass)

  Glucocorticoids: Permissive for optimal growth: ↑GHRH receptor & GH synthesis. High concentrations inhibit growth (e.g. pharmacological doses to treat asthma & inflammations)

  
• Local Growth Factors / Mitogens


  • Epidermal growth factor: Polypeptide (produced by many normal cell types and by some tumors), Growth, proliferation and differentiation of mesenchymal and epithelial cells

  Nerve growth factor: Polypeptide (secreted by neuron's target), Growth & differentiation of sympathetic and sensory neurons

  Fibroblast growth factor: Polypeptide (heparin-binding proteins), wound healing, angiogenesis, limb formation

  Platelet-derived growth factor: Polypeptide (carried in the a-granules of platelets), Initiates replication of connective tissue cells in response to trauma
• Growth Hormone Excess


  Hypersecretion of growth hormone: if in childhood, then rapid, excessive growth; body remains in proportion (gigantism), if after adolescence, then bones can not lengthen but will thicken; increased soft tissue formation (acromegaly)
• Gigantism


  • Robert Wadlow 8ft 11", Sandy Allen 7ft 7"
• Acromegaly


  Cause: pituitary adenoma after adolescence, Effect: Bones grow in thickness not length (cranium, nose, supraorbital ridges, mandible, vertebrae), Enlargement of hands and feet, elongation of ribs (barrel-chested appearance), Enlarged tongue, liver, kidneys, heart, Diabetes, Treatment: somatostatin analogs, surgery
• Acromegaly and oral health


  • Enlarged lips and tongue (macroglossia), Increased spaces between teeth, Mandible growth after puberty – class 3 malocclusion; prognathism, Accelerated tooth eruption in children, Facial features become broader and thickened, Maxillary sinuses are larger, Hyperglycaemia / diabetes mellitus – increased risk of gingivitis and periodontal disease
• Acromegaly


  GHRH (+), GHIH (-), Hypothalamus, Anterior Pituitary (somatotropes), Liver, IGFs, tissue
• Growth hormone deficiency (pituitary dwarfism)


  Cause: Congenital defect, pituitary tumor or trauma causing panhypopituitarism (¯ secretion of all anterior pituitary hormones) or isolated GH (or IGF-I) deficiency, Effect: Slow and reduced growth (to ~4 ft), Proportional appearance, Craniofacial dymorphisms include frontal bossing, midfacial hypoplasia and micrognathia, If panhypopituitarism, will also have hypothyroidism, hypogonadism and low glucocorticoids, Treatment: human GH ± thyroxine, cortisol
• Other types of dwarfism


  • African pygmies have IGF-I (or receptor) deficiency, Primordial dwarfism does not respond to GH treatments (due to mutation of pericentrin gene causing abnormal cell division), Laron dwarfism is characterised by abnormal GH receptors, Cartilage-hair hypoplasia is due to mutations in the ribonuclease mitochondrial RNA-processing (RMRP) gene