Tissue deiodinase activity during prolonged critical illness: effects of exogenous thyrotropin-releasing hormone and its combination with growth hormone-releasing peptide-2.
Debaveye. Yves Y; Ellger. Björn B; Mebis. Liese L; Van Herck. Erik E; Coopmans. Willy W; Darras. Veerle V; Van den Berghe. Greet G
Key Findings
- Critical illness suppresses liver deiodinase 1 (D1) activity and tends to increase deiodinase 3 (D3), lowering T3 and raising rT3.
- Infusion of TRH alone restores D1 activity and brings T3 levels back to normal.
- Combining GHRP‑2 with TRH normalizes D3 activity and prevents the rT3 increase seen with TRH alone.
Practical Outcomes
- GHRP‑2 appears to influence thyroid hormone conversion, especially when paired with TRH, suggesting it could modulate metabolism beyond just boosting growth hormone. However, the data come from an animal model of severe illness, so there’s no direct protocol for healthy individuals. Anyone considering GHRP‑2 should be aware it might affect thyroid status and monitor hormone levels if using it long‑term.
Summary
In sick rabbits, the liver's ability to turn inactive thyroid hormone into the active form (T3) drops, while the enzyme that makes an inactive form (rT3) goes up. Giving the hormone-releasing peptide TRH fixes the active‑hormone maker, and adding GHRP‑2 on top of TRH stops the rise in the inactive hormone. This shows GHRP‑2 can affect thyroid hormone balance, but the study is in a severe illness model and not directly about healthy people.
Abstract
Prolonged critical illness is characterized by reduced pulsatile TSH secretion, causing reduced thyroid hormone release and profound changes in thyroid hormone metabolism, resulting in low circulating T(3) and elevated rT(3) levels. To further unravel the underlying mechanisms, we investigated the effects of exogenous TRH and GH-releasing peptide-2 (GHRP-2) in an in vivo model of prolonged critical illness. Burn-injured, parenterally fed rabbits were randomized to receive 4-d treatment with saline, 60 microg/kg.h GHRP-2, 60 microg/kg.h TRH, or 60 microg/kg.h TRH plus 60 microg/kg.h GHRP-2 started on d 4 of the illness (n = 8/group). The activities of the deiodinase 1 (D1), D2, and D3 in snap-frozen liver, kidney, and muscle as well as their impact on circulating thyroid hormone levels were studied. Compared with healthy controls, hepatic D1 activity in the saline-treated, ill animals was significantly down-regulated (P = 0.02), and D3 activity tended to be up-regulated (P = 0.06). Infusion of TRH and TRH plus GHRP-2 restored the catalytic activity of D1 (P = 0.02) and increased T(3) levels back within physiological range (P = 0.008). D3 activity was normalized by all three interventions, but only addition of GHRP-2 to TRH prevented the rise in rT(3) seen with TRH alone (P = 0.02). Liver D1 and D3 activity were correlated (respectively, positively and negatively) with the changes in circulating T(3) (r = 0.84 and r = -0.65) and the T(3)/rT(3) ratio (r = 0.71 and r = -0.60). We conclude that D1 activity during critical illness is suppressed and related to the alterations within the thyrotropic axis, whereas D3 activity tends to be increased and under the joint control of the somatotropic and thyrotropic axes.
Study Information
pubmed
2005
2005-09-08T00:00:00.000Z
10.1210/en.2005-0963