Thyrotropin regulation of cyclic adenosine monophosphate production in human coronary artery smooth muscle cells

Thyroid disease has been associated with the occurrence of pathophysiologic changes in the vasculature that may result in part from altered serum thyr oid hormone and serum lipid levels. Thyrotropin (TSH) levels are also alter ed in thyroid disease, but a direct effect of TSH on vascular smooth muscle has not previously been considered. In the present study, human coronary a rtery smooth muscle cells (CASMC) were induced into two morphologically dis tinct forms by culturing in either (1) growth factor supplemented, 0.5% ser um medium (SmGM-3) or (2) basal medium (SmBM) plus 10% fetal bovine serum ( FBS). Intracellular cyclic adenosine monophosphate (cAMP) accumulation was determined by radioimmunoassay after exposure to increasing doses of bovine TSH. Cells grown in SmBM/10% FBS for 3 days exhibited a dose-dependent inc rease in intracellular cAMP that reached a level 10 times higher than basel ine at the highest dose examined (100 mIU/mL). In contrast, cells grown in SmGM-3 medium exhibited no change in intracellular cAMP on exposure to incr easing TSII. Low serum (0.5% FBS) reduced the ability of TSH to stimulate c AMP above the control value in CASMC. Pretreatment of CASMC with either tra nsforming growth factor-beta 1 (TGF-beta 1) or tumor necrosis factor-alpha (TNF-alpha) lowered basal levels of cAMP production, but did not inhibit th e ability of TSH to stimulate cAMP production. Human, but not rat aortic sm ooth muscle cells in culture also responded to TSH with a significant incre ase in cAMP. The results of this study suggest that TSH may exert direct ef fects on vascular smooth muscle mediated by adenylate cyclase activation th at could conceivably affect the progression of vascular disease associated with thyroid dysfunction.