Growth hormone-releasing hormone (GHRH, Sermorelin) and Growth hormone-releasing peptides (GHRPs)

• Overview: GHRH; GHRPs

  • Hypothalamic growth hormone-releasing hormone (GHRH):  pituitary growth hormone (GH) secretion

  • GHRH belongs to a family of molecules including:

    • Secretin, VIP, gastric inhibitory peptide (GIP), glucagon.

  • Major site of GHRH production: arcuate nucleus hypothalamus.

  • GHRH receptor:

    • G protein-coupled transmembrane receptor

    • Activation :  ­GH gene transcription, ­synthesis and ­GH release (cAMP mediated)

• Chemistry, Pharmacokinetics, and Pharmacodynamics:  GHRH and GHRP

  • Chemistry: GHRH and GHRP

    • Growth hormone-releasing hormone:

      • 44-amino acid peptide leads to GH release stimulation.

      • Activity is expressed in the first 29-amino acids.

      • Growth-hormon releasing hormone (GHRH) is also known as growth-hormone releasing factor (GRF), GHRF, somatoliberin or somatocrinin.

    • Growth hormone-releasing peptides

      • Groups of small, synthetic peptides

      • Stimulate GH secretion (similar to GHRH)

  • Pharmacokinetics: GHRH and GHRP

    • GHRH: Routes of administration:

      • IV

      • Subcutaneous

      • Intranasal

  • Pharmacodynamics: GHRH and GHRP

    • Stimulation: growth hormone secretion only (anterior pituitary)

• Clinical use:  GHRH and GHRP

  • GHRH: evaluation of short children with subnormal GH response to:

    • Insulin-induced hypoglycemia, oral L-DOPA, IV arginine

    • Normal response in this group:  GH deficiency secondary to hypothalamic dysfunction

    • Subnormal response in this group:   pituitary or hypothalamic dysfunction

    • Growth hormone level increase following GHRH:   favorable clinical response to GHRH treatment

•  Toxicity: GHRH and GHRP

  • Facial flushing; injection site discomfort (nasal GHRP-2 appears to be well tolerated).

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