Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men.
Soule. S S; King. J A JA; Millar. R P RP
Key Findings
- The D‑Ala2 version has about half the metabolic clearance rate of the regular GHRH‑(1‑29) peptide.
- Its disappearance half‑life is longer (6.7 min vs 4.3 min for the native peptide).
- The slower clearance translates into stronger biological activity in humans.
Practical Outcomes
- For biohackers, using the D‑Ala2‑GRF‑1‑29 analog can give a more potent and longer‑lasting GH‑releasing effect, potentially allowing lower or less frequent dosing compared to the unmodified peptide. However, the half‑life is still only minutes, so timing of injections relative to desired GH spikes remains important.
Summary
Adding a D‑alanine at position 2 of the growth‑hormone‑releasing hormone fragment (GRF‑1‑29) makes the peptide stick around in the blood longer and be cleared more slowly, which boosts its ability to raise growth hormone levels.
Abstract
D-Ala2-GHRH-(1-29) has increased binding affinity and exhibits enhanced biological activity in man. It is not known whether changes in the metabolic clearance of this and other GHRH analogs contribute to their increased biological activity. GHRH-(1-29)-NH2 and D-Ala2-GHRH-(1-29)-NH2 were administered by constant iv infusion at a rate of 25 ng/kg.min to 10 normal men. Blood was sampled during the 90-min infusion and for 20 min afterward and assayed for the infused analog. The MCR of the D-Ala2 analog (mean +/- SE) was significantly less (21 +/- 1.2 mL/kg.min) than that of GHRH-(1-29)-NH2 (39.7 +/- 3.9 mL/kg.min; P < 0.001). The disappearance half-time of the D-Ala2 analog was 6.7 +/- 0.5, whereas that of GHRH-(1-29)-NH2 was 4.3 +/- 1.4 min (P < 0.05). These findings demonstrate that the D-Ala2 substitution contributes to the enhancement of biological activity by reducing metabolic clearance.
Study Information
pubmed
1994
10.1210/jcem.79.4.7962295