A synthetic peptide corresponding to amino acid residues 90 to 95 of humanfollicle-stimulating hormone beta-subunit delays the onset of puberty in female Swiss Webster mice

We have recently reported that a synthetic peptide corresponding to amino a cid residues 81-95, a receptor-binding region of the human FSH-beta-subunit , and a subdomain within this region, hFSH-beta-(90-95) (DSTDCT), prolonged vaginal estrus when administered intraperitoneally (ip) to normally cyclin g Swiss Webster mice. These results were similar to those we reported for a synthetic peptide corresponding to hFSH-beta-(34-37) [TRDL, a subdomain wi thin receptor-binding region hFSH-beta-(33-53)] in the same model system. T RDL also accelerated the onset of puberty in immature mice. We now report t he effects of hFSH-beta-(90-95) in prepubertal female mice. in two separate experiments, a single ip injection of 200 mu g/g body weight (BW) hFSH-bet a-(90-95) in phosphate buffered saline (PBS, vehicle) administered to mice on day 28 delayed first vaginal estrus by 3 days in 50% (4/8) and 62.5% (6/ 8) when compared to mice given vehicle alone on day 28. Vaginal opening was also delayed in mice receiving hFSH-beta-(90-95) when compared to mice inj ected with vehicle alone. Serum estradiol levels of vehicle-injected contro l mice in first vaginal estrus were three-fold higher than in mice treated with hFSH-beta-(90-95), whose vaginal smears showed no evidence of first es trus. No significant differences in ovarian or uterine weights, or serum pr ogesterone levels, were observed between vehicle-injected control mice achi eving first vaginal estrus acid mice receiving hFSH-beta-(90-95) in whom fi rst estrus was delayed. The contrasting effects on the onset of puberty of hFSH-beta-(90-95) (delay) and hFSH-beta-(34-37) (acceleration) may reflect synthetic peptide binding to different domains of the FSH receptor, resulti ng in variable post-binding effects. These results are consistent with our earlier study suggesting that FSH-beta-subunit-related synthetic peptides c an induce significant in vivo effects on the onset of puberty in female mic e. (C) 1999 Elsevier Science B.V. All rights reserved.