TY - JOUR
T1 - Altered thyroid axis function in Lewis rats with genetically defective hypothalamic CRH/VP neurosecretory cells
AU - Whitnall, Mark H.
AU - Smallridge, Robert C.
PY - 1997
Y1 - 1997
N2 - Lewis rats display hyporesponsive hypothalamo-pituitary-adrenocortical (HPA) axes, overproduction of cytokines, and susceptibility to inflammatory disease. The Lewis corticotropin-releasing hormone (CRH) neurosecretory system contains normal numbers of vasopressin (VP)-deficient axon varicosities, but abnormally sparse VP-containing varicosities in the external zone of the median eminence, compared to the normoresponsive Sprague Dawley (SD), Wistar and Fischer 344 strains. Since VP may act as a thyrotropin-releasing factor, we hypothesized that thyroid axis responsivity may be altered in Lewis rats. T3, T4 and TSH were measured by radioimmunoassay, and free T4 by equilibrium dialysis, in adult male Lewis and SD rats. One h cold (5°C) induced significant increases in T3, T4 and TSH levels in Lewis rats but not in SD rats. Ninety min insulin- induced hypoglycemia (1 IU/kg, ip) induced a significant T3 increase in Lewis rats and a significant T4 increase in SD rats. Two h after ip LPS (0.25 or 0.75 mg/kg), T4 levels fell significantly in Lewis rats but not in SD rats. TSH decreases were significant in Lewis rats after 0.75 mg/kg and in SD rats after 0.25 mg/kg. Baseline hormone levels were generally higher in Lewis rats; the differences were significant for T3 and T4 in the insulin experiments and for T3, T4 and free T4 in the LPS experiments. The data suggest that reduced inhibition from the adrenocortical axis in Lewis rats leads to hyperresponsivity of the thyroid axis to cold, and greater LPS-induced decreases in T4 levels, probably due to an exaggerated inhibitory cytokine response.
AB - Lewis rats display hyporesponsive hypothalamo-pituitary-adrenocortical (HPA) axes, overproduction of cytokines, and susceptibility to inflammatory disease. The Lewis corticotropin-releasing hormone (CRH) neurosecretory system contains normal numbers of vasopressin (VP)-deficient axon varicosities, but abnormally sparse VP-containing varicosities in the external zone of the median eminence, compared to the normoresponsive Sprague Dawley (SD), Wistar and Fischer 344 strains. Since VP may act as a thyrotropin-releasing factor, we hypothesized that thyroid axis responsivity may be altered in Lewis rats. T3, T4 and TSH were measured by radioimmunoassay, and free T4 by equilibrium dialysis, in adult male Lewis and SD rats. One h cold (5°C) induced significant increases in T3, T4 and TSH levels in Lewis rats but not in SD rats. Ninety min insulin- induced hypoglycemia (1 IU/kg, ip) induced a significant T3 increase in Lewis rats and a significant T4 increase in SD rats. Two h after ip LPS (0.25 or 0.75 mg/kg), T4 levels fell significantly in Lewis rats but not in SD rats. TSH decreases were significant in Lewis rats after 0.75 mg/kg and in SD rats after 0.25 mg/kg. Baseline hormone levels were generally higher in Lewis rats; the differences were significant for T3 and T4 in the insulin experiments and for T3, T4 and free T4 in the LPS experiments. The data suggest that reduced inhibition from the adrenocortical axis in Lewis rats leads to hyperresponsivity of the thyroid axis to cold, and greater LPS-induced decreases in T4 levels, probably due to an exaggerated inhibitory cytokine response.
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U2 - 10.1080/07435809709031863
DO - 10.1080/07435809709031863
M3 - Article
C2 - 9430824
AN - SCOPUS:0031444303
SN - 0743-5800
VL - 23
SP - 365
EP - 376
JO - Endocrine Research
JF - Endocrine Research
IS - 4
ER -