title: Thyrotropin regulation of cyclic adenosine monophosphate production in human coronary artery smooth muscle cells.
abstract: Thyroid disease has been associated with the occurrence of pathophysiologic changes in the vasculature that may result in part from altered serum thyroid hormone and serum lipid levels. Thyrotropin (TSH) levels are also altered in thyroid disease, but a direct effect of TSH on vascular smooth muscle has not previously been considered. In the present study, human coronary artery smooth muscle cells (CASMC) were induced into two morphologically distinct forms by culturing in either (1) growth factor supplemented, 0.5% serum 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 increase in intracellular cAMP that reached a level 10 times higher than baseline 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 increasing TSII. Low serum (0.5% FBS) reduced the ability of TSH to stimulate cAMP above the control value in CASMC. Pretreatment of CASMC with either transforming growth factor-beta1 (TGF-beta1) or tumor necrosis factor-alpha (TNF-alpha) lowered basal levels of cAMP production, but did not inhibit the ability of TSH to stimulate cAMP production. Human, but not rat aortic smooth muscle cells in culture also responded to TSH with a significant increase in cAMP. The results of this study suggest that TSH may exert direct effects on vascular smooth muscle mediated by adenylate cyclase activation that could conceivably affect the progression of vascular disease associated with thyroid dysfunction.
authors.affiliation: Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA. DSELLITTI@USUHS.MIL
authors.forename: D F
authors.initials: DF
authors.lastname: Sellitti
authors.forename: D
authors.initials: D
authors.lastname: Dennison
authors.forename: T
authors.initials: T
authors.lastname: Akamizu
authors.forename: S Q
authors.initials: SQ
authors.lastname: Doi
authors.forename: L D
authors.initials: LD
authors.lastname: Kohn
authors.forename: H
authors.initials: H
authors.lastname: Koshiyama
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011989:Receptors, Thyrotropin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013972:Thyrotropin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000199:Actins; D016895:Culture Media, Serum-Free; D006133:Growth Substances; D011989:Receptors, Thyrotropin; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D013972:Thyrotropin; D000242:Cyclic AMP