Previous studies suggested that the inhibition of thyroxine (T₄) release by α₁-adrenoceptor and muscarinic receptor stimulation results in activated protein kinase C (PKC) from mouse and guinea pig thyroids. In the present study, the effect of carbachol, methoxamine, phorbol myristate acetate (PMA), and R59022 on the release of T₄ from the mouse, rat, and guinea pig thyroids was compared to clarify the role of PKC in the regulation of the release of T₄. The thyroids were incubated in the medium containing the test agents, samples of the medium were assayed for T₄ by EIA kits. Forskolin, an adenylate cyclase activator, chlorophenylthio-cAMP sodium, a membrane permeable analog of cAMP, and isobutyl-methylxanthine, a phosphodiesterase inhibitor, like TSH (thyroid stimulating hormone), enhaced the release of T₄ from the mouse, rat, and guinea pig thyroids.
Methoxamine, an α₁-adrenoceptor agonist, inhibited the TSH-stimulated release of T₄ in mouse, but not rat and guinea pig thyroids. In contrast, carbachol, a muscarinic receptor agonist, inhibited the release of T₄ in guinea pig, but not mouse and rat thyroids. These inhibition were reversed by prazosin, an α₁-adrenoceptor antagonist or atropine, a muscarinic antagonist or M₁- and M₃-muscarinic antagonists, in mouse or guinea pig thyroids. In addition, staurosporine, a PKC inhibitor, reversed methoxamine or carbachol inhibition of TSH stimulation. Furthermore, PMA, a PKC activator, and R59022, a diacylglycerol (DAG) kinase inhibitor, inhibited the TSH-stimulated release of T₄ in mouse, rat, and guinea pig thyroids. These inhibition were blocked by staurosporine. These findings suggest that the activation of receptor or DAG inhibits TSH-stimulated T₄ release through a PKC-dependent mechanism in thyroid gland.
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