DEHYDROEPIANDROSTERONE-SULFATE DOES NOT PREVENT SPONTANEOUS AND IODINE-INDUCED LYMPHOCYTIC THYROIDITIS AND DIABETES-MELLITUS IN THE BB WOR RAT/

Chronic feeding of dehydroepiandrosterone (DHEA) and its sulfated meta bolite, dehydroepiandrosterone sulfate (DHEAS), has previously been re ported to decrease hyperglycemia, obesity, cancer, and autoantibody ge neration 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 carr ied out to determine whether lame amounts of DHEAS given orally would prevent the occurrence of spontaneous and iodine-induced autoimmune ly mphocytic thyroiditis (LT) and/or spontaneous insulin-dependent diabet es mellitus (DM) in male and female BB/Wor rats, DHEAS was administere d 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 re ceived iodine in the drinking water to enhance the incidence and inten sity of LT. Onset of DM requiring protamine zinc insulin and its maint enance dose were assessed. Rats were killed at 90 or 120 days of age a nd blood, thyroid, adrenals, pancreases, testes, and ovaries were remo ved. Serum glucose, DHEA, DHEAS, thyroxine (T-4), tri-iodothyronine (T -3) and thyrotropin (TSH) concentrations were measured in all rats in both experiments. Serum DHEAS concentrations were 10-fold higher in th e rats given the steroid by gavage or in the diet compared with levels in control rats. DHEAS administered over a prolonged period of time h ad no significant effect on body weight, incidence and severity of DM, incidence and intensity of spontaneous and iodine-induced LT, and thy roid, pancreas and testes weights but did significantly decrease adren al and ovarian weights. Serum T-4, T-3, and TSH concentrations were si milar 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 imm unosuppressive effects in other animal models.