Involvement of the cyclic-AMP-dependent protein kinase A pathway in thyroxine effects on calcitonin secretion from TT cells.
Previous studies have demonstrated that plasma calcitonin is lower in hypothyroid patients and that thyroxine stimulates the human thyroid to release calcitonin. Therefore, thyroid hormones may regulate the secretion of calcitonin, but further work is needed to address this possibility in more detail. TT cells, a model of human thyroid C cells, were incubated in a medium containing vehicle, thyroxine, or thyroxine methyl-hemisuccinate-bovine serum albumin (BSA-L-T(4), thyroxine was immobilized and linked to BSA); then, the levels of secreted calcitonin (hCT), calcitonin mRNA, and cAMP were measured. To study links that connect the cAMP-dependent protein kinase A (PKA) pathway to the observed thyroxine effects, cells were treated with either vehicle or thyroxine plus SQ22536 [an adenylyl cyclase (AC) inhibitor], KT5720 (a PKA inhibitor), or 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor). The activity levels of AC and PKA, and secreted calcitonin were then measured. The results indicate that thyroxine increases calcitonin secretion, cellular cAMP accumulation, and the activities of AC and PKA, but does not increase hCT mRNA levels in TT cells. BSA-L-T(4) also increases calcitonin secretion. These effects are inhibited by SQ22536, and KT5720 and suggest that the nongenomic thyroxine effects that stimulate calcitonin secretion from TT cells involve the cAMP-dependent PKA pathway.
Lu
C-C
CC
Division of Research and Development, Mackay Medicine, Nursing and Management College, Taipei, Taiwan, ROC. cclu@ms1.url.com.tw
Tsai
S-C
SC
D002116:Calcitonin / Q000378:metabolism*; D045744:Cell Line, Tumor; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction; D013961:Thyroid Gland / Q000201:enzymology* / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism*
D002116:Calcitonin; D017868:Cyclic AMP-Dependent Protein Kinases; D013974:Thyroxine