Endocrine and metabolic effects of growth hormone (GH) compared with GH-releasing peptide, thyrotropin-releasing hormone, and insulin infusion in a rabbit model of prolonged critical illness.
Weekers. Frank F; Michalaki. Marina M; Coopmans. Willy W; Van Herck. Eric E; Veldhuis. Johannes D JD; Darras. Veerle M VM; Van den Berghe. Greet G
Key Findings
- GHRP‑2 + TRH increased pulsatile endogenous rabbit GH and TSH release on day 1.
- After 4 days, the combo raised T4 and T3 levels and boosted liver type 1 deiodinase while lowering type 3 deiodinase, enhancing T4→T3 conversion.
- Mortality, organ function, hyperglycemia, and insulin needs were similar across GHRP‑2+TRH, rhGH, and saline groups.
- High‑dose rhGH suppressed the animal’s own GH, raised IGF‑I more, but did not affect thyroid hormones or deiodinase activity.
Practical Outcomes
- For the self‑directed health community, the data suggest that GHRP‑2 can stimulate the GH axis and improve thyroid hormone activation without obvious glucose toxicity in a stressed animal model. However, because the experiment used critically ill rabbits, the findings are only modestly informative for healthy humans and should be applied cautiously, with close monitoring of blood sugar and thyroid markers if experimenting.
Summary
In sick rabbits, giving GHRP‑2 together with TRH lifted the body’s own growth‑hormone and thyroid‑stimulating hormone without causing extra high blood sugar or death, unlike giving a big dose of synthetic growth hormone. The combo also nudged the liver to turn more T4 into the active hormone T3. However, the study was done in a critical‑illness model, not healthy people, so the results can’t be directly copied to everyday biohacking.
Abstract
Treatment with recombinant human GH (rhGH) increases the mortality of critical illness. We postulated that combined GH-releasing peptide-2 (GHRP-2), TRH, and insulin infusion is a less toxic anabolic strategy through a putative inability to overstimulate the GH axis and a capacity to normalize thyroid hormone concentrations while foregoing excessive hyperglycemia. Burn-injured, parenterally fed, New Zealand White rabbits were randomized to receive 4-d treatment with saline (n=8); 60 microg/kg.h GHRP-2 and 60 microg/kg.h TRH, i.v. (n=9); or 3.5 mg/kg rhGH, s.c. (n=7). In the GHRP-2+TRH group, insulin was adjusted to maintain blood glucose below 180 mg/dl. Endocrine function and biochemical organ system function markers were studied. Animals were killed for assay of deiodinase activity in snap-frozen liver. Mortality, organ system function, hyperglycemia, and insulin requirement were equal in the three groups. GHRP-2+TRH increased pulsatile rabbit GH (rGH) and TSH release on d 1. After 4 d, rGH secretion and T4 and T3 concentrations were elevated, with a significant increase in hepatic activity of type 1 deiodinase and a decrease in type 3 deiodinase. Exogenous rhGH suppressed endogenous rGH secretion and increased IGF-I more than GHRP-2+TRH without altering thyroid hormone levels. Unlike GHRP-2+TRH, rhGH down-regulated liver type 3 deiodinase and did not affect type 1 deiodinase. We conclude that in experimentally induced critical illness, GHRP-2+TRH reactivated the GH and TSH axes and altered liver deiodinase activity, driving T4 to T3 conversion. In contrast to the human model, high dose rhGH was not rapidly lethal in this rabbit model. Whether this is explained by lack of rhGH-induced insulin resistance and hyperglycemia remains unclear.
Study Information
pubmed
2003
2003-10-09T00:00:00.000Z
10.1210/en.2003-1005