The shed thyrotropin receptor is primarily a carboxyl terminal truncated form of the A subunit, not the entire A subunit

The TSH receptor (TSHR) sheds its A subunit, particularly when cells are cu ltured in serum-poor medium. This shed A subunit is reported to be smaller than the cell-associated receptor because of the loss of glycan without cha nge in its polypeptide core. Contrary to previous deductions, we now find t hat the 'small' shed A subunit has lost a glycan moiety because of the prot eolytic clipping of a small C-terminal fragment containing an Asn-linked gl ycan. Moreover, this lost peptide fragment contains cysteine residues likel y involved in A. subunit linkage to the membrane-associated B subunit. Prog ressive lowering of the serum concentration in culture medium accentuates t he process. Therefore,'small' A subunit shedding does not appear related to a physiological mechanism involving disulfide bond reduction. On the other hand, we detected, for the first time, shedding of a lesser amount of norm al-sized, in addition to small, A subunits, especially by cells cultured in standard serum concentrations. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.