Synthesis of the luteinizing releasing hormone of the hypothalamus and its hormonal activity.

The decapeptide amide and acid of LH-RH/FSH-RH were synthesized and bioassayed in rats. The structure pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH3 was made by conventional synthesis of pGlu-His-Trp coupled with the heptapeptide synthesized on solid state resin. Bioassays were performed in ovariectomized rats given 50 mcg estradiol benzoate and 25 mg progesterone 72 hours before by injecting the peptides and sampling the jugular vein then assaying LH by double antibody radioimmunoassay. The decapeptide amide was effective from 25 ng to 10 mcg. At 1 or 10 mcg LH level was elevated about 25 fold for 30-60 minutes and decreased to about 10 fold in 2 hours. The decapeptide-OH was active but only at about 1000 times the amide dose. Considering prior work with the tetrapeptide pGlu-Tyr-Arg-Trp-NG2 the authors proposed that the conformation of Tyr and Arg are fundamental in its function.

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