Altered thyroid axis function in lewis rats with genetically defective hypothalamic CRH/VP neurosecretory cells

Abstract

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 thyrotropinreleasing 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 insulininduced 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.