In vivo effects of lamprey GnRH-I and cyclized analogs: a structure-activity study.
Lamprey GnRH-I and lamprey GnRH-III are the only two members of the GnRH family to have substitutions in the sixth position, Glu6 and Asp6, respectively; all other GnRH peptides have Gly in the sixth position suggesting a different conformational structure. Thus, a structure-activity study of lamprey GnRH-I or analogs that were cyclized or with sixth position substitutions were determined in vivo in adult female sea lamprey, Petromyzon marinus. The following analogs which were tested, ([D-Glu6]-GnRH-I; cyclo-[D-Glu6-Trp7-Lys8]-GnRH-I; or cyclo-[Glu6-Trp7-Lys8]-GnRH-I), significantly elevated plasma estradiol compared to controls. However, [D-Glu6]-lamprey GnRH-I was the only analog to significantly stimulate ovulation while another analog [Gly6]-lamprey GnRH-I significantly delayed ovulation. These data suggest that the sixth position of lamprey GnRH is critical for function.
Department of Biochemistry and Molecular Biology, University of New Hampshire, Durham, NH 03824, USA.
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Sower
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Goodman
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Nishiuchi
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D003500:Cyclization; D004958:Estradiol / Q000097:blood; D005069:Evaluation Studies as Topic; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007798:Lampreys / Q000378:metabolism*; D008969:Molecular Sequence Data; D010062:Ovulation Induction; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship
D000596:Amino Acids; C097498:lamprey GnRH-I; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D011761:Pyrrolidonecarboxylic Acid