A synthetic peptide corresponding to amino acid residues 90 to 95 of human follicle-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 acid 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 cycling Swiss Webster mice. These results were similar to those we reported for a synthetic peptide corresponding to hFSH-beta-(34-37) [TRDL, a subdomain within receptor-binding region hFSH-beta-(33-53)] in the same model system. TRDL also accelerated the onset of puberty in immature mice. We now report the effects of hFSH-beta-(90-95) in prepubertal female mice. In two separate experiments, a single ip injection of 200 microg/g body weight (BW) hFSH-beta-(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 injected with vehicle alone. Serum estradiol levels of vehicle-injected control 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 estrus. No significant differences in ovarian or uterine weights, or serum progesterone levels, were observed between vehicle-injected control mice achieving first vaginal estrus and mice receiving hFSH-beta-(90-95) in whom first 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, resulting in variable post-binding effects. These results are consistent with our earlier study suggesting that FSH-beta-subunit-related synthetic peptides can induce significant in vivo effects on the onset of puberty in female mice.
Grasso
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Department of Biochemistry and Molecular Biology, Albany Medical College, NY 12208, USA.
Reichert
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D000818:Animals; D004958:Estradiol / Q000097:blood; D004971:Estrus / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000737:chemistry*; D037201:Follicle Stimulating Hormone, beta Subunit; D006801:Humans; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D011374:Progesterone / Q000097:blood; D012741:Sexual Maturation / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects
D037201:Follicle Stimulating Hormone, beta Subunit; D010446:Peptide Fragments; D011374:Progesterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone