Accession Number : ADA328836


Title :   Altered Thyroid Axis Function in Lewis Rats with Genetically Defective Hypothalamic CRH/VP Neurosecretory Cells.


Descriptive Note : Special Publication,


Corporate Author : ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD


Personal Author(s) : Whitnall, Mark H. ; Smallridge, Robert C.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA328836


Report Date : AUG 1997


Pagination or Media Count : 14


Abstract : Lewis rats display a hyporesponsive hypothalamo-pituitary-adrenocortical (HPA) axis, 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 vasopressin-containing varicosities in the external zone of the median eminence, compared to the normoresponsive Sprague Dawley (SD), Wistar, and Fischer 344 strains. Since vasopressin may act as a thyrotropin-releasing factor, we hypothesized that thyroid axis responsivity may be altered in Lewis rats. T(sub 3), T(sub 4), and the thyroid-stimulating hormone (TSH) were measured by radioimmunoassay, and free T(sub 4) by equilibrium dialysis in adult male Lewis and SD rats. Exposure to cold (5 deg C) for 1 h induced significant increases in T(sub 3), T(sub 4), and TSH levels in Lewis rats but not in SD rats. Ninety min of insulin-induced hypoglycemia (1 IU/kg, ip) caused a significant T(sub 3) increase in Lewis rats and a significant T(sub 4) increase in SD rats. Two h after intraponeal administration of lipopolysaccharide (LPS; (0.25 or 0.75 mg/kg)), T(sub 4) levels fell significantly in Lewis rats but not in SD rats. TSH decreases were significant in Lewis rats after 0.75 mg/kg LPS and in SD rats after 0.25 mg/kg. Baseline hormone levels were generally higher in Lewis rats; the differences were significant for T(sub 3) and T(sub 4) in the insulin experiments and for T(sub 3), T(sub 4), and free T(sub 4) 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 T(sub 4) levels, probably due to an exaggerated inhibitory cytokine response.


Descriptors :   *THYROID GLAND, *NERVE CELLS, *CELLS(BIOLOGY), *ADRENOCORTICOTROPIC HORMONE, *RADIOIMMUNOASSAY, *PITUITARY HORMONES, *HYPOTHALAMUS, FUNCTIONS, HORMONES, RATS, DISEASES, EQUILIBRIUM(GENERAL), DISPLAY SYSTEMS, REDUCTION, BASE LINES, EXTERNAL, MALES, INHIBITION, NUMBERS, INFLAMMATION, ADULTS, SECRETION, LIPOPOLYSACCHARIDES, INSULIN, ADRENAL CORTEX, DIALYSIS.


Subject Categories : BIOCHEMISRTY
      ANATOMY AND PHYSIOLOGY
      RADIOBIOLOGY


Distribution Statement : APPROVED FOR PUBLIC RELEASE