Alteration in the transmission of TSH-message to thyroid target in a transplantable rat thyroid tumor.
Plasma membranes derived from a transplantable rat thyroid tumor (line 1-5G in Wollman's classification), which is unresponsive to thyrotropin (TSH) but is responsive to dibutyryl 3', 5' cAMP, have been evaluated to localize the defect. TSH binding in tumor plasma membrane is slightly lower than in normal rat thyroid membranes. No change in affinity, but simply a lower capacity was observed. The glycoprotein component of the TSH receptor exhibits similar binding and solubilization properties to the glycoprotein component derived from normal rat thyroid. Analogously to normal rat thyroid membranes, gangliosides more complex than N-acetylneuraminylgalactosylglucosyl-ceramide (GM3) are also present in tumor line 1-5G membranes. Phospholipid content of tumor line 1-5G is 50% lower than that of normal rat thyroid. At variance also with normal rat thyroid, 32P incorporation in tumor line 1-5G phospholipids such as phosphatidylserine and phosphatidylethanolamine is not modified after in vitro incubation with TSH. An even more pronounced effect by TSH on 32P incorporation into phosphatidylinositol is evident in tumor line 1-5G by comparison to normal. The 1-5G thyroid tumor membranes has a 12-fold higher basal adenylate cyclase activity than that of rat thyroid membranes. The high basal adenylate cyclase activity is associated with high ADP ribosylation activity. Both enzymes of tumor are only slightly responsive to TSH. These results suggest that the block in the transmission of TSH message to the cell machinery is localized to the regulatory domains between TSH receptor and adenylate cyclase catalytic subunit.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005732:Gangliosides / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D010761:Phosphorus Radioisotopes / Q000378:metabolism; D051381:Rats; D013964:Thyroid Neoplasms / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology*
D005732:Gangliosides; D010743:Phospholipids; D010761:Phosphorus Radioisotopes; D000246:Adenosine Diphosphate Ribose; D013972:Thyrotropin; D000262:Adenylyl Cyclases