Hypothalamo-hypophysial-thyroid axis in streptozotocin-induced diabetes

Diabetes mellitus is frequently associated with reduced levels of TSH, PRL, GH, and gonadotropins. In this study we have wanted to determine whether chemically induced diabetes mellitus is associated with a decreased hypothalamic release of TRH. Male rats were made diabetic with streptozotocin (STZ; 65 mg/kg), whereas controls received vehicle. After 2 weeks, STZ diabetic rats had 25% lower body weights, 3.5-fold higher blood glucose, and 40-60% lower plasma TSH, T3, and T4 levels than controls. The plasma T4 dialyzable fraction had increased 2.5-fold in STZ diabetic rats, and the plasma free T4 concentration was similar to that in controls. Thus, treatment with STZ results in decreased plasma TSH and T4 levels, but does not reduce free T4 concentrations. The content of TRH in hypothalami of 2-week STZ diabetic rats was similar to that in controls, but in vitro these hypothalami released less TRH than those of control rats. In 2-week STZ diabetic rats, TRH in hypophysial stalk blood was 30% lower than that in control rats. The in vitro TRH secretion from hypothalami of untreated rats was dependent on the glucose concentrations in the incubation medium; increasing the glucose concentration from 10 to 30 mM did not alter TRH secretion, but basal TRH release increased in the absence of glucose. In conclusion, STZ-induced diabetes in the rat is associated with reduced hypothalamic secretion of TRH, which, in turn, may be responsible for the reduced plasma TSH and thyroid hormone levels. Furthermore, it is suggested that the inhibitory effect of STZ-induced diabetes on TRH secretion is probably not due to hyperglycemia.