FOLLITROPIN SIGNAL-TRANSDUCTION - ALTERNATIVE SPLICING OF THE FSH RECEPTOR GENE PRODUCES A DOMINANT-NEGATIVE FORM OF RECEPTOR WHICH INHIBITS HORMONE ACTION

We have studied the functional properties of an alternately spliced fo rm of sheep testicular FSH receptor cDNA that codes for a protein simi lar to a previously described active receptor but differs in the carbo xy terminus in sequence and is also shorter by 25 residues. The recept or expressed in HEK 293 cells fails to activate adenylate cyclase. Cot ransfection of stably expressing cells bearing FSH receptor that activ ates (G(s)) adenylate cyclase with the altered receptor cDNA abrogates hormone response. In cells expressing this cDNA, FSH also inhibited c yclic AMP accumulation induced by non hormonal agents such as forskoli n and cholera toxin which bypass the receptor. We propose that this al tered receptor is a dominant negative receptor which may be coupled to G(i) protein(s) or other inhibitory mechanisms. (C) 1996 Academic Pre ss, Inc.