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 form of sheep testicular FSH receptor cDNA that codes for a protein similar to a previously described active receptor but differs in the carboxy terminus in sequence and is also shorter by 25 residues. The receptor expressed in HEK 293 cells fails to activate adenylate cyclase. Cotransfection of stably expressing cells bearing FSH receptor that activates (Gs) adenylate cyclase with the altered receptor cDNA abrogates hormone response. In cells expressing this cDNA. FSH also inhibited cyclic AMP accumulation induced by non hormonal agents such as forskolin and cholera toxin which bypass the receptor. We propose that this altered receptor is a dominant negative receptor which may be coupled to G1 protein(s) or other inhibitory mechanisms.