Triiodothyronin (T3) time and dose dependently stimulates cortisol secretion from bovine adrenocortical cells in primary culture

Thyroid hormones have been shown to modulate hormone production in steriodogenic tissues, especially the gonads. Little is known about the influence of thyroid hormones on adrenocortical function. Some early clinical studies describe an accelerated cortisol production and degradation in hyperthyroid states. Wether Triiodthyronin increases cortisol secretion directly or indirectly via the pituitary-adrenal axis is not known. In order to address this question, we investigated the effect of triiodothyronin (T3) on cortisol and cAMP synthesis from adult bovine adrenocortical cells in primary culture. In time-course experiments, cells were treated with physiological doses of T3 (1 and 3 ng) with or without the addition of ACTH (1nM) for up to 96h. T3 stimulated basal cortisol secretion maximally 2.2 and 4.3-fold (1ng T3 and 3ng T3 respectively). Cortisol secretion was induced significantly already after 24 hours and reached its maximum effect after 48h. In combination with ACTH, T3 synergistically increased cortisol secretion from 4.3-fold (ACTH 1nM) to 10.8-fold of untreated control levels. Dose-response experiments did show a significant stimulatory effect of T3 on cortisol secretion at doses as low as 0.25 ng and tretment with 0.1 ng T3 caused a half-maximal stimulation. The maximum stimulatory effect was reached at doses of 3 ng T3. Stimulation with concentrations greater than 3 ng/ml did not elicit a further increase in cortisol secretion. When cAMP secretion of bovine adrenocortical cells was measured, a strong, 3.2-fold stimulatory effect was observed when cells were treated with ACTH (1 nM) alone. Combination of ACTH with T3 (3ng) did not induce a further increase in cAMP-secretion and no effect on cAMP-secretion was found when bovine adrenocortical celle were treated with T3 alone. In summary our results demonstrate for the first time that Triiodthyronin time and dose dependently enhances cortisol secretion of bovine adrenocortical cells independently of ACTH and via cAMP independent pathways.