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.
Sower
S A
SA
Department of Biochemistry and Molecular Biology, University of New Hampshire, Durham, NH 03824, USA.
Goodman
M
M
Nishiuchi
Y
Y
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