CONTROL OF THYROID-SECRETION - EFFECTS OF STIMULATORS OF PROTEIN-KINASE-C, THYROTROPIN, AND CALCIUM MOBILIZATION ON SECRETION OF IODINATED COMPOUNDS FROM SHEEP THYROID-CELLS

We have compared and contrasted the abilities of TSH and agents capabl e of discretely activating the cAMP-dependent protein kinase, protein kinase C, or calcium mobilization to influence the secretion of iodina ted compounds from cells prelabeled with iodide and blocked from furth er organification with methimazole. We found that calcium mobilization induced by A23187, protein kinase C activation induced by 12-O-tetrad ecanoyl phorbol 13-acetate (TPA) and TSH all stimulated the secretion of iodinated compounds. The effects of TSH were mimicked by forskolin and those of TPA by a synthetic diacylglycerol, sn-1,2-dioctanoylglyce rol. The effects of TPA were partially inhibited by staurosporine wher eas those of TSH were not. Epidermal growth factor and norepinephrine were without effect on thyroid secretion. The effects of A23187 and TP A were synergistic. The effects of TSH and TPA were not and the increa sed secretion induced by either agent was partially prevented by the c ombination. Preincubation of cells with TSH desensitized the cells to further stimulation by TSH but the stimulatory effects of TPA were una ffected. Exposure of cells to medium without calcium also induced loss of iodinated compounds which was partially prevented by TSH or forsko lin but not TPA. TSH did not stimulate the rapid production of inosito l trisphosphate production. We conclude that the mechanisms by which T SH (through stimulation of cAMP) and stimulators of other intracellula r pathways exert their effects on secretion of iodocompounds, differ. Activation of protein kinase C and acute production of inositol trisph osphate do not appear to be involved in the mechanism of action of TSH in stimulating thyroid secretion but calcium mobilization is implicat ed.