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Diminished Binding of Thyroid-stimulating Hormone in a Transplantable Rat Thyroid Tumor as a Possible Cause of Hormone Unresponsiveness¹

Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R., Istituto di Patologia Generate, Universitá di Napoli, Naples, Italy

The adenylate cyclase activity and the binding of ¹²⁵I-labeled thyroid-stimulating hormone (TSH) of normal and tumor rat thyroid plasma membranes were compared. No significant difference in the basal and fluoride-sensitive adenylate cyclase activity between normal and tumor plasma membranes was observed. Thyroid plasma membranes responded to TSH, whereas the enzyme from the tumor plasma membranes was TSH insensitive. Thyroid plasma membranes bound ¹²⁵I-TSH. Tumor plasma membranes bound ¹²⁵I-TSH poorly. At the highest concentration of unlabeled TSH used, 80% of the ¹²⁵I-TSH that was bound to thyroid plasma membranes was displaced, whereas only 10% of the 125I-TSH bound to tumor plasma membranes was displaced. Therefore, it seems likely that the failure of this tumor to respond to TSH is due to an alteration in the functional unit of membrane adenylate cyclase at the level of the receptor subunit.

¹ This work was partly supported by the Italy-United States Cooperation Program in Science (No. 20413154.26368).

Received 4/ 7/75. Accepted 8/ 4/75.