Dehydroepiandrosterone sulfate does not prevent spontaneous and iodine-induced lymphocytic thyroiditis and diabetes mellitus in the BB/Wor rat

Department of Medicine, University of Massachusetts Medical School, Worcester, USA.

Chronic feeding of dehydroepiandrosterone (DHEA) and its sulfated metabolite, dehydroepiandrosterone sulfate (DHEAS), has previously been reported to decrease hyperglycemia, obesity, cancer, and autoantibody generation in a number of animal models and to increase muscle mass and physiological and psychological well-being in elderly humans, although these latter studies remain controversial. The present study was carried out to determine whether large amounts of DHEAS given orally would prevent the occurrence of spontaneous and iodine-induced autoimmune lymphocytic thyroiditis (LT) and/or spontaneous insulin-dependent diabetes mellitus (DM) in male and female BB/Wor rats. DHEAS was administered by gavage (44 mg/rat/day) or in the chow (133 mg/rat/day) to LT- and DM-prone rats from 30 to 120 days of life; some of these rats also received iodine in the drinking water to enhance the incidence and intensity of LT. Onset of DM requiring protamine zinc insulin and its maintenance dose were assessed. Rats were killed at 90 or 120 days of age and blood, thyroid, adrenals, pancreases, testes, and ovaries were removed. Serum glucose, DHEA, DHEAS, thyroxine (T4), tri-iodothyronine (T3) and thyrotropin (TSH) concentrations were measured in all rats in both experiments. Serum DHEAS concentrations were 10-fold higher in the rats given the steroid by gavage or in the diet compared with levels in control rats. DHEAS administered over a prolonged period of time had no significant effect on body weight, incidence and severity of DM, incidence and intensity of spontaneous and iodine-induced LT, and thyroid, pancreas and testes weights but did significantly decrease adrenal and ovarian weights. Serum T4, T3, and TSH concentrations were similar in control and DHEAS-treated rats. In conclusion, DHEAS did not prevent the occurrence of iodine-induced or spontaneous autoimmune LT or spontaneous DM in the BB/Wor rat, at variance with its reported immunosuppressive effects in other animal models.