Résumé
The synthetic peptide encompassing the 75-89 sequence of the alpha-subunit of human glycoprotein hormones (h alpha 75-89) binds to LH receptors and stimulates testosterone secretion in rat Leydig cells in vitro. We show that synthetic peptides with the corresponding sequences from equine and porcine alpha-subunits exhibit the same activity as the human one in contrast to peptides of identical sizes but unrelated structures, All these data support the view that the alpha 75-89 sequences in LH molecules or part(s) of them are involved in receptor binding and target cell activation. The tetrapeptide Glu-Asn-His-Thr (ENHT) representing the 81-84 sequence of the alpha subunits in the three species was found to be totally inactive in the two assays, By contrast, a complex mixture of random peptides, produced by introducing the 12 amino-acids of the h alpha 75-89 sequence at each of the 15 steps of peptide synthesis was found to be as active as the authentic h alpha 75-89 peptide in the two assays. This could suggest that it is the composition rather than the sequence of the alpha 75-89 region that is essential in hormone functions but this is very unlikely. Another possibility is that the activity of the mixture of random peptides could be due to short peptide sequences present in very low amounts but exhibiting much higher potency than the authentic sequences. More likely, all the pentadecapeptides described here interact with the LH receptor with low affinity in a way not related to the specific high-affinity binding of LH itself. These data point out the difficulties and the limitations of the synthetic peptide approach to delineate the functional regions in glycoprotein hormones.