ISOLATION OF TSH-RESPONSIVE HUMAN THYROCYTES-ANALYSIS OF VARIOUS THYROID TUMOURS

Abstract

ABSTRACT A method for the isolation of hormone-responsive thyrocyte suspensions from human tumours is described. Cells from normal and adenomatous thyroid tissue responded to thyroid stimulating hormone (TSH) by a concentration-dependent increase in cAMP. Bovine TSH usually produced half-maximal elevation of cAMP levels at concentrations between 2 and 4 mU/ml. Human TSH caused half-maximal stimulation at 3–8 times lower concentrations indicating considerable species specificity of the human TSH receptor. Other hormones were without influence except prostaglandin E1 (PGE1) which evoked moderate elevations of the cAMP levels. Kinetic analyses of various thyroid tumours revealed marked differences in TSH induced increases in the intracellular cAMP levels with respect to the time course as well as to the extent of the maximal response. Theophylline, which by itself had a rather small effect on basal cAMP levels, acted synergistically with TSH in most cases, leading to values up to 20 times above the control values. The kinetics also indicated the existence in stimulated cells of two cAMP pools exhibiting different susceptibility to phosphodiesterase. Cells from adenomatous goitres with hyperplasia exhibited significantly lower basal cAMP levels than thyrocytes from the other goitres and from normal tissue. Other classes of thyroid tumours also showed characteristic differences with regard to basal cAMP and degree of stimulation by TSH and theophylline.