Acute effects of thyroid hormones on the production of adrenal cAMP and corticosterone in male rats

The acute effects of thyroid hormones on glucocorticoid secretion were studied. Venous blood samples were collected from male rats after they received intravenous 3,5,3'-triiodothyronine (T₃) or thyroxine (T₄). Zona fasciculata-reticularis (ZFR) cells were treated with adrenocorticotropic hormone (ACTH), T₃, T₄, ACTH plus T₃, or ACTH plus T₄ at 37°C for 2 h. Corticosterone concentrations in plasma and cell media, and also adenosine 3',5'-cyclic monophosphate (cAMP) production in ZFR cells in the presence of 3-isobutyl-1-methylxanthine, were determined. The effects of thyroid hormones on the activities of steroidogenic enzymes of ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. Administration of T₃ and T₄ suppressed the basal and the ACTH-stimulated levels of plasma corticosterone. In ZFR cells, both thyroid hormones inhibited ACTH-stimulated corticosterone secretion, but the basal corticosterone was inhibited only with T₃ >10^-10 M or T₄ >10^-8 M. Likewise, T₃ or T₄ at 10^-7 M inhibited the basal- and ACTH-stimulated levels of intracellular cAMP. Physiological doses of T₃ and T₄ decreased the activities of 3β-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11β- hydroxylase. These results suggest that thyroid hormones counteract ACTH in adrenal steroidogenesis through their inhibition of cAMP production in ZFR cells.