NDLI: Decapeptides as effective agonists from L-amino acids biologically equivalent to the luteinizing hormone-releasing hormone.

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Decapeptides as effective agonists from L-amino acids biologically equivalent to the luteinizing hormone-releasing hormone.

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Decapeptides as effective agonists from L-amino acids biologically equivalent to the luteinizing hormone-releasing hormone.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bowers, C. Y. Folkers, K. Tang, P. F. Kubota, M.
Abstract	Apparently, no agonist has been found that is comparable in potency to the luteinizing hormone-releasing hormone (LHRH) for release of LH and follicle-stimulating hormone (FSH) without substitutions with unnatural or D forms of natural amino acids. Of 139 known 'agonist analogs' of LHRH, two were active in the range of 65%. The four LHRHs known to occur in nature involve a total of six amino acids (Tyr, His, Leu, Trp, Arg, Gln) in positions 5, 7, and 8. There are 16 possible peptides with these six amino acids in positions 5, 7, and 8, of which 4 are the known LHRHs, and 2 more were synthesized. We have synthesized the 10 new peptides and assayed 11 in vivo and in vitro, and we found not only 1 but a total of 5 that have activity equivalent to or greater than that of LHRH for the release of LH and/or FSH under at least one assay condition. These five are as follows: [His5,Trp7,Gln8]LHRH; [His5,Trp7,Leu8]LHRH; [His5,Trp7]LHRH; [Trp7]LHRH; [His5]LHRH. Two of these five agonists variably released relatively more FSH than LH. One or more of these five agonists may occur in nature and one may be follicle-stimulating hormone-releasing hormone. The two peptides with Gln8 and Leu8, if occurring in nature, may have different receptors according to radioreceptor assays and to the ratio of LH/FSH release in vivo. These structures are a basis for the design of antagonists without Arg8 toward avoiding histamine release. Complete inhibition of LH and FSH release in vivo may be induced by joint use of Arg8 and Gln8 or Leu8 antagonists. These potent agonists, related to LHRH, may be therapeutically useful in disorders of reproduction, the central nervous system, and for the control of hormone-dependent carcinomas.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	4
Volume Number	83
Language	English
Publisher	National Academy of Sciences
Publisher Date	1986-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gonadotropin-Releasing Hormone Analogs & Derivatives Peptide Fragments Pharmacology Amino Acid Sequence Animals Follicle Stimulating Hormone Secretion Luteinizing Hormone Chemical Synthesis Pituitary Gland, Anterior Salmon Secretory Rate Drug Effects Stimulation, Chemical Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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