Activation of somatostatin-receptor subtype-2/-5 suppresses the mass, frequency, and irregularity of growth hormone (GH)-releasing peptide-2-stimulated GH secretion in men.
Iranmanesh. Ali A; Bowers. Cyril Y CY; Veldhuis. Johannes D JD
Key Findings
- Octreotide (a somatostatin‑2/5 receptor agonist) reduced baseline GH levels and the size of GH bursts.
- When GHRP‑2 was used, octreotide cut GH burst mass by ~35%, reduced pulse frequency by ~40%, and made the release pattern more regular (lower approximate entropy).
- Octreotide had little effect on GH pulse frequency or regularity when only GHRH (or GHRH + GHRP‑2) was given, indicating a selective interaction with GHRP‑2‑driven secretion.
Practical Outcomes
- For biohackers using GHRP‑2 to raise GH, the study suggests that endogenous somatostatin can dampen the response, so timing doses when somatostatin is low (e.g., after fasting or during deep sleep) may improve effectiveness. Conversely, using somatostatin analogs like octreotide would counteract GHRP‑2 benefits and is not advisable. Future protocols might explore somatostatin antagonists or lifestyle tweaks to minimize this feedback.
Summary
In healthy men, giving the somatostatin‑like drug octreotide sharply cut down the amount, frequency, and regularity of growth‑hormone spikes that are normally triggered by the peptide GHRP‑2. The drug didn’t change how often GH pulses happened when no GHRP‑2 was given, but it did blunt the GHRP‑2‑driven bursts. This shows that the body’s own somatostatin system can strongly limit the GH‑boosting effect of GHRP‑2.
Abstract
Somatostatin antagonizes the stimulatory actions of GHRH and GH-releasing peptides (GHRPs). However, precisely how the inhibitory susceptibilities of the two secretagogues differ is not clear. One interpretative difficulty is that native somatostatin activates six different receptor subtypes. The present study adopts the complementary strategy of enforcing feedback inhibition via the preferential somatostatin receptor subtype 2 and 5 (SSTR-2/-5) agonist, octreotide. We postulated that putative SSTR-2/-5 agonism would unmask secretagogue-selective interactions in the control of GH secretory burst mass, frequency, and/or regularity. To this end, 10 healthy men each underwent eight randomly ordered, separate-day, fasting morning infusion sessions. Interventions comprised sc administration of octreotide (1 microg/kg), followed by bolus iv injection of saline, GHRH (1 microg/kg), GHRP-2 (1 microg/kg), or both peptides. Compared with placebo, the SSTR-2/-5 agonist reduced fasting GH concentrations from 0.27 +/- 0.07 to 0.12 +/- 0.02 microg/liter (P = 0.020), GH secretory burst mass from 2.7 +/- 0.65 to 0.55 +/- 0.11 microg/liter (P = 0.013), and basal GH secretion from 0.24 +/- 0.043 to 0.11 +/- 0.015 microg/liter.100 min (P = 0.0063). The foregoing outcomes were selective, because octreotide did not alter GH secretory burst frequency (3.1 +/- 0.5 vs. 3.3 +/- 0.21 events/3 h) or the regularity of the GH release process (approximate entropy, 0.58 +/- 0.048 vs. 0.68 +/- 0.064). In the GHRP-2-stimulated setting, presumptive SSTR-2/-5 agonism suppressed all three GH secretory burst masses, from 28 +/- 3.2 to 18 +/- 2.0 (P = 0.045); GH pulse frequency, from 3.3 +/- 0.30 to 2.0 +/- 0.18 (P = 0.0025); and the irregularity (approximate entropy) of GH release, from 0.648 +/- 0.049 to 0.433 +/- 0.047 (P < 0.01). In contrast, in the GHRH and combined GHRH/GHRP-2-stimulated contexts, octreotide decreased only GH secretory burst mass (P = 0.047). In summary, the present data indicate that GH secretory burst mass, frequency, and orderliness are subject to interactive control by at least SSTR-2/-5-dependent feedback and GHRP-dependent feedforward signals.
Study Information
pubmed
2004
10.1210/jc.2004-0205