Abstract
A convenient method for evaluating the biological activity of luteinizing hormone-releasing hormone (LHRH) antagonists was devised. Pregnant mare's serum gonadotropin (PMSG) treatment of immature rats is known to stimulate follicular growth and estrogen production, that in turn stimulates the release of LHRH which triggers an ovulatory discharge of luteinizing hormone (LH) from the pituitary. The present bioassay of the antagonists is based on the inhibition of ovulation in the PMSG-treated rats. Twenty-eight-day-old Sprague Dawley rats maintained under a light period of 12 h/day (lights on at 0630 h) were given 10 IU of PMSG s.c. at 0930 h. On Day 30 of age the antagonist was given s.c. at 1430 h. The rats were killed on the following morning and the oviducts examined for the presence of ova. In addition, the antagonists were compared in their ability to inhibit serum testosterone levels in adult male rats. In the PMSG-treated rats the order of ovulation-inhibiting potency of the following antagonists was: [Ac-D-NAL(2)1,4FD-Phe2,D-Trp3,D-Arg6]-LHRH (LHRH-1) greater than [Ac-delta 3 Pro1,4FD-Phe2,D-NAL(2)3.6]-LHRH (LHRH-2) greater than [Ac-delta 3 Pro1,4FD-Phe2,D-Trp3,6]-LHRH (LHRH-3). The order of potency was confirmed by their antitesticular effects in adult male rats.
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