Absence of high-affinity binding sites for beta-adrenergic blockers and lack of adenyl cyclase stimulation to beta-adrenergic stimulators in most normal and adenomatous human thyroid tissues.
To determine whether the beta-blocking drug propranolol had any physiologic effect on normal (n = 14) and adenomatous (n = 15) human thyroid tissues, experiments were performed to study the binding of the beta-blockers 125I-iodocyanopindolol (125I-ICYP) and 125I-iodohydroxybenzylpindolol (125I-IHYP) and the stimulation of adenyl cyclase (AC) by isoproterenol. 125I-ICYP and 125I-IHYP failed to show high-affinity binding in 27 of 29 specimens, whereas two (one normal and one adenomatous) thyroid tissues demonstrated high-affinity binding (Kd 5.5 +/- 1 X 10(-9) M) for 125I-ICYP. Thyroid-stimulating hormone (0.3 IU/ml), guanosine triphosphate (10(-4) M), and Gpp (NH)p(10(-4) M) stimulated AC in all thyroid tissues, although in two tissues (normal) Gpp (NH)p failed to cause a significant increase. Isoproterenol (10(-4) M), in contrast, had no effect on basal AC activity or on guanosine triphosphate, and Gpp (NH) p stimulated AC activity in 26 of the 29 thyroid tissues. In one of the two tissues that increased AC in response to isoproterenol, the beta-blocking drugs propranolol hydrochloride, bunitrolol hydrochloride, and tolilprolol hydrochloride decreased AC stimulation to isoproterenol at concentrations of 10(-6) M (p less than 0.05). Higher concentrations of propranolol (10(-4) - 10(-2) M) decreased AC stimulation to thyroid-stimulating hormone (p less than 0.01), not only in this responsive tissue but also in tissues that failed to demonstrate high-affinity binding for 125I-ICYP and AC stimulation to isoproterenol (p less than 0.01). Thus most normal and adenomatous human thyroid tissues lack beta-receptors and a functioning beta-receptor AC system. High concentrations of propranolol in vitro decreased AC response by thyroid-stimulating hormone, but this is probably a nonreceptor-mediated effect.
D000236:Adenoma / Q000201:enzymology* / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013961:Thyroid Gland / Q000201:enzymology / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; C011878:iodohydroxybenzylpindolol; D020120:Iodocyanopindolol; D006160:Guanosine Triphosphate; D013972:Thyrotropin; D011433:Propranolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol