Thyroid hormone receptors are down-regulated in skeletal muscle of patients with non-thyroidal illness syndrome secondary to non-septic shock.
OBJECTIVE
Non-thyroidal illness syndrome (NTIS) is related to changes in thyroid hormone (TH) physiology. Skeletal muscle (SM) plays a major role in metabolism, and TH regulates SM phenotype and metabolism. We aimed to characterize the SM of non-septic shock NTIS patients in terms of: i) expression of genes and proteins involved in TH metabolism and actions; and ii) NFKB's pathway activation, a responsible factor for some of the phenotypic changes in NTIS. We also investigated whether the patient's serum can induce in vitro the effects observed in vivo.


METHODS
Serum samples and SM biopsies from 14 patients with non-septic shock NTIS and 11 controls. Gene and protein expression and NFKB1 activation were analyzed by quantitative PCR and immunoblotting. Human SM cell (HSkMC) cultures to investigate the effects of patient's serum on TH action mediators.


RESULTS
Patients with non-septic shock NTIS showed higher levels of pro-inflammatory cytokines than controls. Expression of TRβ (THRB), TRα1 (THRA), and retinoid X receptor γ (RXRG) was decreased in NTIS patients. RXRA gene expression was higher, but its protein was lower in NTIS than controls, suggesting the existence of a post-transcriptional mechanism that down-regulates protein levels. NFKB1 pathway activation was not different between NTIS and control patients. HSkMC incubated with patient's serum increased TH receptor and RXRG gene expression after 48  h.


CONCLUSIONS
Patients with non-septic shock NTIS showed decreased expression of TH receptors and RXRs, which were not related to increased activation of the NFKB1 pathway. These findings could not be replicated in cultures of HSkMCs incubated in the patient's serum.
Lado-Abeal
J
J
Division of Endocrinology, Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, STOP 9410, Lubbock, Texas 79430-9410, USA. joaquin.lado@ttuhsc.edu
Romero
A
A
Castro-Piedras
I
I
Rodriguez-Perez
A
A
Alvarez-Escudero
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D005067:Euthyroid Sick Syndromes / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012769:Shock / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012772:Shock, Septic / Q000150:complications / Q000378:metabolism / Q000473:pathology; D037021:Thyroid Hormone Receptors alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000502:physiology; D037042:Thyroid Hormone Receptors beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000502:physiology
D012333:RNA, Messenger; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta