Growth Hormone (Somatotropin, GH)

• Overview: GH

  • Peptide hormone: synthesized in anterior pituitary

  • Growth promotion:

    • At open epiphyses: mechanism

      • Stimulation of insulin-like growth factor I (IGF-I, somatomedins C)

  • Promotes lipolysis: adipose tissue

  •  Promotes skeletal muscle growth

• Growth Hormone: Regulation

  Type of Agent	Stimulation (+)	Inhibition (-)
  Hypothalamic factors	GHRH	Somatotropin
  Biogenic amines	α2-adrenergic receptor agonists (e.g. clonidine)	β-adrenergic agonists
  	β-adrenergic receptor antagonists (e.g., propranolol)	α2-adrenergic receptor antagonists (e.g., yohimbine)
  	5-HT (serotonin) stimuli (e.g.,L-tryptophan)	5-HT (serotonin) receptor antagonists (e.g., cyproheptadine, methysergide)
  	Dopaminergic stimuli (e.g., L-DOPA, apomorphine, bromocriptine)	Dopaminergic antagonists (e.g., chlorpromazine)
  Hormones	Decreased IGF-I	Increased IGF-I
  	Estrogen	Progestins
  	Vasopressin	Glucocorticoids (acutely, glucocorticoids increase growth hormone release)
  	Glucagon (cholinergic-mediated)
  	Hypoglycemia (α-adrenergic mediated)	Increased blood sugar
  	Decreased free fatty acids	Increased free fatty acids
  	Amino acid (arginine; cholinergic-mediated)
  Others	Exercise--α-adrenergic mediated	Antimuscarinic agents (e.g., atropine)
  	Stress--α-adrenergic mediated
  	Sleep -cholinergic-mediated
  	Cholinergic-muscarinic stimulation (e.g., pyridostigmine)

  Adapted from Table 328-3 Biller, Beverly, M. K. and Daniels, Gilbert, H. Neuroendocrine Regulation and Diseases of the Anterior Pituitary and Hypothalamus, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, p. 1979.

• Chemistry:  growth hormone

  • 191-amino acid peptide.

  • Structurally similar to prolactin and chorionic somatomammotropin.

  • Recombinant DNA growth hormone:

    • Somatotropin (191-amino acid form).

    • Somatrem (192 amino acid form (additional methionine).

• Pharmacokinetics:  growth hormone

  • Plasma have life: 20-25 minutes

  • Clearance: hepatic

  • Administration: intramuscular (peak plasma concentration: 2-4 hours)

• Pharmacological Effects:  growth hormone

  • Initial insulin-like effects

    • Increase glucose uptake

    • Increased amino acid uptake

    • Decreased lipolysis

  • Delayed anti-insulin effect including impaired glucose uptake and increased lipolysis

  • Promotes longitudinal growth indirectly through:

    •  Somatomedins, insulin-like growth factors (IGFs)

    • ­  GH stimulates growth plate cartilage and liver synthesis of:

      •  IGF-I I and IGF-I II

    • Somatomedins: mediator of processes promoting bone growth as reflected by increased of DNA thymidine incorporation and increased RNA uridine incorporation. 

      • These effects are associated with:

        • Increased cellular proliferation.

        • Increased proline to hydroxyproline conversion (cartilage synthesis)

  • GH deficiency:  reduced somatomedin :  short stature

    • Short stature:

      • IGF-I deficiency (in the presence of high GH):  Laron dwarfism

      •  Absence of IGF-I pubertal surge (pygmies)

    • Criteria for growth hormone deficiency:

      •  Growth rate index < 4 cm/year

      •  Lack of increase serum GH following growth hormone secretagogue challenge

    • Causes of congenital growth hormone deficiencies:

      • Most frequent cause is lack of hypothalamic growth hormone-releasing factors, usually due to pit-I gene abnormality.

      • Hypophyseal-pituitary disease, e.g. craniopharyngiomas

    • Growth hormone deficiency manifestation of the newborn include: 

      •  Seizures

      •  Hypoglycemia

    • GH deficiency often associated with multiple pituitary hormonal deficiencies

  • Growth Hormone-Responsive Clinical Conditions

    • GH deficiencies

    • Some non-GH deficiencies manifested by delayed bone age/slow growth rate + GH:  increased growth (short-term GH treatment)

    • Girls with Turner's syndrome: high-dose treatment effective

•   Adverse Effects:  growth hormone

  • Following rapid growth

    • Slipped capital femoral epiphyse:  limp; lower extremity pain (rare)

  • Leukemia incidence (slight increase, may not be causal)

  • Screening suggested for hypothyroidism and diabetes during GH treatment

• Impairment of GH response

  • Untreated hypothyroidism

  • Diabetes mellitus/diabetes insipidus

Primary Reference: Fitzgerald, P.A. and Klonoff, D.C. Hypothalamic and Pituitary Hormones, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 603-618.

Primary Reference: Biller, Beverly M. K. and Daniels, Gilbert, H. Neuroendocrine Regulation and Diseases of the Anterior Pituitary and Hypothalamus, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1972-1998

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