A synthetic peptide corresponding to hFSH-beta-(81-95) has thioredoxin-like activity.

The thioredoxin-like activity of human follicle stimulating hormone (hFSH), hFSH-beta-(83-88) peptide amide (hFSH-beta-(83-88) which has a sequence similar to the thioredoxin active center (-His-Cys-Gly-Lys-Cys-Asp-)) and thioredoxin-(31-36)-peptide amide (TD-(31-36) which contains the redox-active dithiol of thioredoxin (-Trp-Cys-Gly-Pro-Cys-Lys-)) was characterized by their ability to reactivate reduced and denatured bovine pancreatic ribonuclease (RNase). This assay reflects the recently recognized ability of thioredoxin to catalyze disulfide bond formation in proteins. Compared to uncatalyzed refolding of reduced, denatured substrate, hFSH was approximately 10-fold more active than thioredoxin on a molar basis. The catalytic activity of hFSH-beta-(83-88) and TD-(31-36) was equivalent to that of an equimolar concentration of thioredoxin. Screening of 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit indicated that hFSH-beta-(81-95), which contains the sequence similar to the thioredoxin active center within a receptor-binding region of the hFSH-beta-subunit, possesses strong thioredoxin-like activity and was more active than an equimolar concentration of thioredoxin. In contrast, hFSH-beta-(33-53), a thiol-containing peptide which corresponds to a second FSH receptor-binding domain but lacks the sequence similar to the thioredoxin active center, was inactive. Synthetic peptide amides corresponding to other regions of hFSH-beta-subunit were less effective than hFSH-beta-(81-95) in reactivating reduced and denatured RNase. Our data provide evidence that the recently reported thioredoxin-like catalytic activity of FSH may be due, at least in part, to the redox-active dithiol present within a receptor-binding domain of its beta-subunit, and thus may have a physiological role in receptor binding or signal transduction.