Recombinant human IGF-I does not modify the ACTH and cortisol responses to hCRH and hexarelin, a peptidyl GH secretagogue, in humans.
Gianotti. L L; Ramunni. J J; Lanfranco. F F; Maccagno. B B; Giordano. R R; Broglio. F F; Maccario. M M; Muller. E E EE; Ghigo. E E; Arvat. E E
Key Findings
- IGF‑I injection increased circulating IGF‑I by about 77% without altering baseline ACTH or cortisol.
- CRH and hexarelin each produced similar increases in ACTH and cortisol.
- Pretreating with IGF‑I did not change the ACTH or cortisol responses to either CRH or hexarelin.
- IGF‑I pretreatment significantly reduced the GH response to hexarelin.
Practical Outcomes
- For biohackers using hexarelin to boost growth hormone, taking IGF‑I beforehand may dampen that GH effect, so timing or avoiding simultaneous IGF‑I use could be important. The lack of impact on cortisol suggests IGF‑I won’t add stress‑related side effects when combined with hexarelin.
Summary
Giving a dose of recombinant IGF‑I raises blood IGF‑I levels but doesn’t change the body's baseline stress hormones (ACTH and cortisol). Both CRH and the GH‑releasing peptide hexarelin normally spike ACTH and cortisol, and IGF‑I pretreatment doesn’t affect those spikes. However, IGF‑I does blunt the GH surge that hexarelin normally causes.
Abstract
An inhibitory influence of insulin-like growth factor-I (IGF-I) on hypothalamus-pituitary-adrenal (HPA) axis has been hypothesized. In fact, it has been reported that the rhGH (recombinant human GH)-induced IGF-I increase inhibits both cortisol and GH response to MK-0677, a non-peptidyl GH secretagogue in animals. The aim of this study was to further clarify the inhibitory role, if any, of IGF-I on corticotroph function. We studied the effect of rhIGF-I (recombinant human IGF-I; 20 microg/kg s.c. at -180 min) or placebo on the ACTH and cortisol responses to hCRH (human CRH; 2.0 microg/kg i.v. at 0 min) or hexarelin (HEX; 2.0 microg/kg i.v. at 0 min), a peptidyl GHS, in normal young women. The effect of rhIGF-I on the GH response to HEX was also studied. The subjects were six normal young women [age: 26-35 yr; body mass index (BMI): 19-23 kg/m2] in their early follicular phase. The results showed that after s.c. rhIGF-I administration, circulating IGF-I levels increased approximately 77%, peaking at -60 min and persisting similar up to +120 min. The mean ACTH, cortisol and GH concentrations did not change from -180 to 0 min when evaluated after both placebo or rhIGF-I. CRH and HEX induced similar ACTH (peak vs baseline, mean+/-SE: 47.5+/-10.9 vs 21.3+/-3.0 pg/ml and 30.3+/-6.9 vs 19.2+/-3.8 pg/ml, respectively; p<0.04) and cortisol responses (177.5+/-5.4 vs 109.3+/-10.3 microg/l and 149.4+/-12.3 vs 119.8+/-16.4 microg/l, respectively, p<0.04). RhIGF-I pretreatment did not modify the ACTH and cortisol responses to hCRH (46.0+/-13.8 pg/ml and 181.1+/-16.9 microg/l, respectively) as well as those to HEX (28.8+/-5.0 pg/ml and 144.1+/-16.2 microg/l, respectively). On the other hand, the GH response to HEX was clearly reduced by rhIGF-I (23.9+/-4.7 vs 64.7+/-14.8 microg/l, p<0.05). Our findings show that rhIGF-I-induced increase of circulating IGF-I levels exerts negative feedback action on somatotroph secretion, while it does not modify the corticotroph and the adrenal responsiveness to CRH or hexarelin.
Study Information
pubmed
2001
10.1007/bf03343815