IN-VIVO EFFECTS OF HUMAN FOLLICLE-STIMULATING HORMONE-RELATED SYNTHETIC PEPTIDE HFSH-BETA-(81-95) AND ITS SUBDOMAIN HFSH-BETA-(90-95) ON THE MOUSE ESTROUS-CYCLE

We have previously reported that a synthetic peptide corresponding to amino acid residues 81-95 of the human (h) FSH-beta subunit inhibited binding of [I-125]hFSH to bovine cal testis membranes and stimulated e stradiol biosynthesis in primary cultures of I at Sertoli cells. We ha ve now obtained several lines of evidence demonstrating in vivo effect s of bFSH-beta-(81-95) on the mouse estrous cycle. 1)A single i.p. inj ection of 200 mu g/g BW hFSH-beta-(81-95) significantly (p < 0.001) pr olonged vaginal estrus in comparison to that in vehicle-injected contr ol mice. 2) Vaginal smears taken at estrus from mice given hFSH-beta-( 81-95) were characterized by the complete absence of epithelial casts, a hallmark of spontaneous ovulation in mice. 3) Mice receiving hFSH-b eta-(81-95) had significantly (p < 0.001) lower serum estradiol al: pr oestrus and serum progesterone at diestrus than vehicle-injected contr ol mice. 4) The proestrous effects of estrogen on uterine ballooning a nd weight gain, clearly evident in vehicle-injected control mice, were not observed in mice treated with hFSH-beta-(81-95). A synthetic pept ide corresponding to the carboxy-terminal region of hFSH-beta-(81-95), hFSH-beta-(90-95), inhibited binding of [I-125]hFSH to bovine calf te stis membranes, antagonized FSH-stimulated estradiol biosynthesis by p rimary cultures of rat Sertoli cells, and prolonged vaginal estrus in normally cycling mice. A synthetic peptide corresponding to the amino- terminal domain, hFSH-beta-(81-86), was inactive in vitro and had no e ffect on the mouse estrous cycle. The results of the present study pro vide additional evidence for in vivo effects of FSH-related synthetic peptides.