Comparison of long-acting analogues of luteinizing hormone releasing hormone in man.
Currently, LHRH, when used therapeutically, is given by parenteral injection every 8 h. We have looked at the release of LH and FSH induced by five analogues of LHRH and compared this with gonadotrophin release after synthetic LHRH. The analogues were substituted in position 6 or in positions 6 and 10 and were given intravenously, intranasally or subcutaneously in three separate studies. After intravenous administration of 100 micrograms, all analogues caused greater release of LH and FSH than did synthetic LHRH. Given intranasally in a dose of 500 micrograms, three of the four analogues tested caused greater LH and FSH release than did LHRH. With tryptophan substitution in position 6 (D-TRP6-LHRH), mean LH levels in five subjects were still above the normal range 24 h after a single intranasal dose. The intranasal administration of selected analogues of LHRH has great potential in the treatment of conditions associated with deficient gonadotrophin secretion, provided that pituitary overstimulation, which may eventually lead to a decrease in LH and FSH output by the anterior pituitary, is avoided.
D000281:Administration, Intranasal; D000328:Adult; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone