Effects of phorbol esters on metabolic variables in the thyroid

Since 12-O-tetradecanoyl-phorbol-13-acetate (TPA) reproduced some of the effects of TSH on phosphorylation of polypeptides in the thyroid, its effects on several thyroid metabolic variables were investigated. Like TSH, TPA stimulated glucose oxidation, iodide organification, and ³²P incorporation into phospholipids in thyroid slices. However, in contrast to TSH, it did not augment cAMP accumulation. An inactive phorbol ester, 4α-phorbol, did not reproduce any of the effects of TPA. An initial incubation of thyroid slices with TPA decreased the stimulation of cAMP, glucose oxidation, and colloid droplet formation induced by TSH. However, an initial incubation with TPA did not modify the subsequent stimulation of glucose oxidation induced by (Bu)₂ cAMP. TPA potentiated the ability of TSH to densensitize the adenylate cyclase system. Although both TPA and TSH increased ³²P incorporation into phospholipids, the patterns were different when individual phps-pholipids were examined. These results indicate another regulatory mechanism for thyroid cell functions independent of cAMP.