Endothelin binding to receptors and endothelin production by human thyroid follicular cells: effects of transforming growth factor-beta and thyrotropin.
Measurable endothelin (ET) was found in serum-free medium of cultured primary thyroid cells derived from human thyroid tissues after 3 days incubation at levels ranging from undetectable to 35 fmol/100,000 cells. Out of 12 thyroid glands studied, 2 responded to transforming growth factor-beta (TGF-beta) treatment with increased ET secretion into medium. Detailed study of cells derived from one of these thyroids showed TGF-beta at 1 ng/ml stimulated ET secretion from 13.7 to 33.3 fmol/100,000 cells after 3 days incubation. Although TSH alone did not significantly modulate ET release into medium, TSH enhanced the stimulatory effect of TGF-beta. A combination of TSH at 1 mU/ml and TGF-beta at 1 ng/ml stimulated ET secretion to 63.8 fmol/100,000 cells after 3 days incubation. Immunostaining studies demonstrated the presence of intracellular immunoreactive ET, largely localized in perinuclear regions, which was greatly stimulated by TSH but not by TGF-beta. These observations suggest that TSH may stimulate only ET synthesis, whereas TGF-beta may stimulate both synthesis and secretion. Binding of [125I]ET-1 to receptor on thyroid cells was dose-dependently stimulated by TGF-beta (0-10 ng/ml) pretreatment for 3 days. Scatchard analysis of competitive binding data from TGF-beta (1 ng/ml)-treated cells indicated that increased binding was the result of increased receptor number and not increased receptor affinity. TSH (0-10 mU/ml), though not as potent as TGF-beta, also dose-dependently stimulated ET binding. Treatment of thyrocytes with 1 mU/ml TSH for 3 days did not significantly affect ET receptor number or binding affinity. These results illuminate aspects of a possible autocrine regulation of ET in the thyroid gland.
Tseng
Y C
YC
Department of Clinical Investigation and Medicine, Walter Reed Army Medical Center, Washington, DC 20307-5001.
Lahiri
S
S
Jackson
S
S
Burman
K D
KD
Wartofsky
L
L
D000236:Adenoma / Q000378:metabolism; D002478:Cells, Cultured; D016232:Endothelins / Q000096:biosynthesis / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006042:Goiter / Q000378:metabolism; D006044:Goiter, Nodular / Q000378:metabolism; D006111:Graves Disease / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D017466:Receptors, Endothelin / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D013954:Thyroglobulin / Q000378:metabolism; D013959:Thyroid Diseases / Q000378:metabolism* / Q000473:pathology; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism; D013972:Thyrotropin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016232:Endothelins; D007457:Iodine Radioisotopes; D017466:Receptors, Endothelin; D016212:Transforming Growth Factor beta; D013972:Thyrotropin; D013954:Thyroglobulin