CHRONIC ETHANOL TREATMENT REDUCES THE RESPONSIVENESS OF THE HYPOTHALAMIC-PITUITARY-THYROID AXIS TO CENTRAL STIMULATION

The hypothalamic-pituitary-thyroid (HPT) axis functions abnormally in man and animals chronically exposed to ethanol. The most consistent ob servation in humans is that the thyrotropin response to thyrotropin-re leasing hormone (TRH) is blunted. We have tested the hypothesis that c hronic ethanol treatment in rats leads to a diminished responsiveness of the hypothalamus to central stimulation. Animals were maintained on 1 of 3 diets for 4 weeks: (1) laboratory chow and water provided ad l ibitum (chow-fed), (2) Sustacal chocolate liquid diet with vitamin mix ture containing 5% (w/v) ethanol provided ad libitum (ethanol), or (3) Sustacal chocolate liquid diet with vitamin mixture containing sucros e substituted isocalorically (35%) for ethanol and provided in amounts matched to a weight-paired, ethanol-treated animal (pair-fed). At the end of 4 weeks, the animals were evaluated for their response to a si ngle injection of ethanol (3 g/kg, ip) and/or exposure to 5 degrees C. Chronic ethanol treatment produced an increase in TRH mRNA in neurons of the paraventricular nucleus and fully blocked the thyrotropic resp onse to cold exposure. However, chronic ethanol-treated animals did no t exhibit altered basal levels of triiodothyronine or thyrotropin, nor did they have an altered response to a single injection of ethanol. T hese data demonstrate that chronic alcohol exposure alters functioning of the hypothalamic-pituitary-thyroid axis at least in part by affect ing TRH neurons of the paraventricular nucleus.