Somatorelin (GHRH 1-44)

Mechanism

Somatorelin (GHRH 1-44) binds to the growth hormone-releasing hormone receptor (GHRHR), a Gs protein-coupled receptor on the surface of somatotroph cells in the anterior pituitary. Binding activates adenylate cyclase, increasing intracellular cyclic AMP (cAMP). Elevated cAMP activates protein kinase A (PKA), which triggers both:

1. Immediate GH release: Exocytosis of pre-formed growth hormone secretory granules.
2. GH gene transcription: PKA phosphorylates CREB (cAMP response element-binding protein), which upregulates GH gene expression, replenishing GH stores.

GHRH also promotes somatotroph proliferation, explaining its role in pituitary somatotroph development. The pulsatile nature of endogenous GHRH release is important: continuous (non-pulsatile) GHRH exposure can paradoxically reduce GH responsiveness through receptor desensitisation.

GHRH action is opposed by somatostatin, which inhibits GH secretion. The interplay between GHRH (stimulatory) and somatostatin (inhibitory) pulses determines the overall pattern of GH secretion. Ghrelin (and GHRPs) stimulate GH through a separate receptor (GHS-R1a), providing a complementary pathway.

Evidence base

Evidence Grade: Moderate

Strengths: Well-characterised physiology; decades of research use as a diagnostic tool; structural template for approved medicines (tesamorelin).

Limitations: Native GHRH itself is not a therapeutic agent due to its 7-minute half-life; most clinical evidence relates to DPP-4-resistant analogues rather than native GHRH.

Key studies and references:

• Guillemin R et al. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982;218(4572):585–587.
• Rivier J et al. Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature. 1982;300(5889):276–278.
• Gelato MC, Merriam GR. Growth hormone-releasing hormone. Annu Rev Physiol. 1986;48:425–438.
• Thorner MO et al. Human pancreatic growth hormone-releasing factor selectively stimulates growth hormone secretion in man. Lancet. 1983;1(8314):24–28.

Protocols

Native GHRH 1-44 has been used in diagnostic stimulation tests at 1 microg/kg intravenous bolus, with growth hormone measured at intervals over 2 hours. Research infusions of 1-2 microg/kg/hour have been used to study pulsatile GH secretion. The 7-minute half-life necessitates continuous infusion or frequent bolus dosing. Most contemporary research uses DPP-4-resistant analogues (sermorelin, tesamorelin, CJC-1295) rather than native GHRH. These protocols are described for research documentation only.

UK legal status

Somatorelin (native GHRH 1-44) is not a licensed medicine in the UK, not MHRA-registered, and not a controlled substance. GHRH analogues (sermorelin, tesamorelin) are POM where licensed. Native GHRH may be sold for research purposes. Most contemporary research uses DPP-4-resistant analogues rather than native GHRH.

Vendor notes

Native GHRH 1-44 is available from some research peptide suppliers, though it is less commonly stocked than its analogues (sermorelin, CJC-1295). Researchers should verify COAs and be aware that DPP-4 sensitivity limits the practical utility of native GHRH in vivo. For most GH-axis research, DPP-4-resistant analogues are more practical.