A synthetic peptide corresponding to human FSH beta-subunit 33-53 binds to FSH receptor, stimulates basal estradiol biosynthesis, and is a partial antagonist of FSH.

We have previously shown that hFSH-beta 34-37 (KTCT) and 49-52 (TRDL) inhibit binding of 125I-hFSH to FSH receptor in calf testis membranes and that hFSH-beta 33-53, which encompasses these tetrapeptides, inhibits binding with increased potency. hFSH-beta 33-53 rapidly dimerizes under conditions utilized in the receptor binding assay (pH 7.5) so that the binding inhibition reported earlier was due to the hFSH-beta 33-53 dimer rather than the monomer. At pH 6.5, conversion to dimer does not occur, and binding inhibition could be unequivocally attributed to the monomer. Radioiodinated and alkylated hFSH-beta 33-53 binds to the FSH receptor with a Kd = (5.5 +/- 1.4) X 10(-5) M. The biological activity of hFSH-beta 33-53 was assessed by its ability to affect the conversion of androstenedione to estradiol in rat Sertoli cells cultures. FSH-beta 33-53 behaved as a partial antagonist of the FSH-induced estradiol synthesis. The required incubation medium, however, contains cystine as well as cystine, which rapidly forms a hFSH-beta Cys-(51)-S-S-Cys derivative at the pH of the incubation, 7.4. When hFSH-beta 33-53 was converted either to the hFSH-beta Cys(51)-S-S-Cys or to a carboxymethylated derivative, inhibition of FSH-induced estradiol synthesis still was observed. This result demonstrates that the free R-SH group at Cys51 is not responsible for the inhibition. FSH-beta 33-53 also significantly stimulated basal levels of estradiol synthesis, but not to maximal levels observed with FSH (partial agonist). Neither the carbohydrate content of hFSH-beta nor the alpha subunit of FSH appears to be essential for signal transduction and expression of the hormone effect of FSH-beta 33-53.