LH and FSH Releasing Activity of Synthetic Luteinizing Hormone Releasing Hormone (LH-RH) and its Analogous Peptides

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LH and FSH releasing activity of synthetic Luteinizing Hormone Releasing Hormone (LH-RH) and its analogous peptides were studied in rats and men. Female rats were ovariectomized in accordance with the modified method of Schally et al., and were used after estrogen-progesterone injection into their femoral vein. The minimum effective amount of LH-RH was 1-5ng (Fig. 1). Both LH and FSH reached the maximum level in 10 min. after the administration and then decreased rapidly (Fig 2). FSH releasing activity was not clear. Analogous peptides were synthesized by substituting one amino acid radical of LH-RH (Pyr1-His2-Trp3-Set4-Tyr5-Gly6-Leu7-Arg8-Pro9-Gly10-NH2) or by making analogous ones of a shorter chain, i. e., The3D-LH-RH, [Phe5]-LH-RH, [Lys8]-LH-RH and Des-Gly10-LH-RH, Des-(7..10)-LH-RH. No LH releasing activity was observed with Des-(7..10)-LH-RH, but other compounds showed 40-80% of the activity of LH-RH (Fig 3). No FSH-releasing activity was noticed (Fig 4). When 100μg LH-RH was injected intravenously to a normal human male, the blood level increased rapidly in 30 min. to about 10 times of the normal level for LH and 2-3 times for FSH, and thereafter it decreased and returned to the normal in 24 hrs. Such an increase of LH and FSH was not noticed in case of patients suffering from Sheehan's disease (Fig 5, 6).
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