Inhibition of corticosterone secretion by thyroxine in male rats

The effects of thyroxine (T ₄ ) on the secretion of corticosterone both in vivo and in vitro in male rats were studied. Rats were thyroidectomized (Tx) or sham Tx. The Tx rats were subcutaneously with T ₄ (20 μg/kg) or saline once daily for two weeks. In an in vitro experiment, adrenal glands were incubated with ACTH, T ₄ , or ACTH plus T ₄ in the presence or absence of 0.5 mM 3-isobutyl-1-methylxanthine (IBMX) at 37°C for 60 min. Medium and ether-extracted plasma samples samples were analyzed for corticosterone by radioimmunoassay (RIA). The accumulation of cyclic adenosine monophosphate (cAMP) in adrenal tissues after incubation with IBMX was measured by RIA. The levels of plasma corticosterone in Tx rats were significantly increased as compared with euthyroid rats. T ₄ replacement in Tx rats restored plasma corticosterone to euthyroid level. Administration of T ₄ in vitro resulted in an inhibition of both basal and ACTH-stimulated release of corticosterone. Both basal and ACTH-stimulated generations of cAMP in adrenal tissues were decreased by T ₄ . These results suggest that T ₄ inhibits the spontaneous and ACTH-stimulated secretion of corticosterone by acting directly at adrenal glands via a decrease in cAMP production.