Biological activity of a synthetic peptide with inhibin-like activity under in vitro and in vivo conditions was compared with three highly potent synthetic lutropin-releasing hormone antagonists. Unlike the synthetic lutropin-releasing hormone antagonists, which effectively inhibited both lutropin and follitropin secretion from the pituitary, the inhibin-like peptide showed a preferential effect by inhibiting follitropin release both in vitro and in vivo. Thus, small peptides such as inhibin-like peptide with a sequence unrelated to lutropinreleasing hormone may provide a basis for design of selective inhibitors of gonadotropin release.Inhibin is a gonadal protein or peptide with the ability to selectively inhibit the secretion of follicle-stimulating hormone (FSH) from the pituitary in various assay systems (1, 2). Advances have been made describing the structures of various molecules with inhibin-like activity. We have reported the isolation, structure, and synthesis of a 31-amino acid peptide with inhibin-like activity (ILP) (3). Subsequently, it was shown to originate from larger molecules (4). Another polypeptide from the same source, though of a different structure, was also reported to exhibit a similar activity (5). Several bull seminal plasma proteins (6-8) with a high degree of homology to fibronectins (8), also inhibit gonadotropin release from the pituitary. Other studies have deduced even more complex structures for inhibin-like protein(s) from ovarian sources based on cDNA sequences (9-11). It is apparent that in the female, besides the ovary, the placenta also has the mRNA for at least one of the chains of human ovarian inhibin protein(s) (12). These reports serve to illustrate the molecular diversity of peptides/proteins that may influence gonadotropin secretion.Lutropin-releasing hormone (LHRH), a decapeptide of hypothalamic origin (13), which arises from a larger precursor, releases both lutropin (LH) and FSH from the pituitary. Since the discovery of the structure of LHRH, more than a thousand analogs (14, 15) displaying potent agonistic or antagonistic activities have been chemically synthesized in the hope of providing new potential approaches to the control of mammalian fertility and the treatment of infertility as well as for therapeutic use in controlling certain types of cancer (16). However, due to the intrinsic LH-and FSH-releasing ability of the decapeptide, there has been no success in producing antagonistic analogs that selectively inhibit LH or FSH release. The object of this investigation was to demonstrate that, under certain in vitro and in vivo conditions, the synthetic ILP could selectively inhibit FSH release while all three LHRH antagonists, which were included for comparison, inhibited the release of both FSH and LH.
MATERIALS AND METHODSILP was chemically synthesized as described (17). The synthetic LHRH analogs (Table 1) were kindly supplied by D. H. Coy.In Vitro Incubation Procedure. Male Swiss albino mice of the Hauska strain were obtained when they were 16 days...