Human follicular gonadotropin releasing peptide analogs. Evaluation of biological (in vitro) and immunological activity.
Human follicular gonadotropin releasing peptide (hF-GRP) has been shown to stimulate pituitary LH and FSH secretion in vitro. Six hF-GRP analogs have been synthesized and evaluated for gonadotropin releasing activity in a rat anterior pituitary primary cell culture system. A tyrosine analog of hF-GRP, [Tyr4]-hF-GRP, retained comparable biological activity in releasing gonadotropins. However, acetylation of hF-GRP in Ac-hF-GRP greatly reduced the in vitro activity. The shorter segments of hF-GRP, hF-GRP-(5-14), and hF-GRP-(10-14), were tested for LH and FSH releasing activity, and it was found that the decapeptide retained moderate activity while the activity of the pentapeptide was markedly lower than hF-GRP. The baboon alpha 1 antitrypsin-(27-40) peptide, b-alpha 1 AT-(27-40), is relatively less potent in releasing LH than hF-GRP. Interestingly, the baboon peptide is more potent (2.5-fold) in releasing FSH under identical conditions. The effect of hF-GRP in releasing LH and FSH was not affected by the presence of LHRH antagonists in cell culture systems. When these peptides were tested for immunological activity in a hF-GRP radioimmunoassay, it was found that hF-GRP and [Tyr4]-hF-GRP have comparable activities. The C-terminal decapeptide of hF-GRP is more active (1.5-fold) in the RIA, and the C-terminal pentapeptide had only one third of the immunoreactivity. The b-alpha 1-AT-(27-40) failed to cross-react in the RIA even at a concentration of 20 micrograms per tube.
Ramasharma
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K
Laboratory of Molecular Endocrinology, University of California, San Francisco.
Yamashiro
D
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Li
C H
CH
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D013329:Structure-Activity Relationship
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone