Tissue deiodinase activity during prolonged critical illness: effects of exogenous thyrotropin-releasing hormone and its combination with growth hormone-releasing peptide-2.
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.
Debaveye
Yves
Y
Department of Intensive Care Medicine, Catholic University of Leuven, Belgium.
Ellger
Björn
B
Mebis
Liese
L
Van Herck
Erik
E
Coopmans
Willy
W
Darras
Veerle
V
Van den Berghe
Greet
G
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002908:Chronic Disease; D016638:Critical Illness; D004338:Drug Combinations; D005740:Gases / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006454:Hemoglobins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007453:Iodide Peroxidase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D010288:Parenteral Nutrition; D011817:Rabbits; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D001786:Blood Glucose; D004338:Drug Combinations; D005740:Gases; D006454:Hemoglobins; D007527:Isoenzymes; D009842:Oligopeptides; D013963:Thyroid Hormones; D013973:Thyrotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C091874:growth hormone-releasing peptide-2; D007453:Iodide Peroxidase