Effects of dose and duration of continuous GnRH-agonist treatment on induction of estrus in beagle dogs: competing and concurrent up-regulation and down-regulation of LH release.
Dose-response estrus-induction trials were conducted during anestrus in 93 treated and 6 control bitches, a continuous administration of the GnRH-agonist lutrelin with a potency 150 x GnRH, and at six different doses from 0.2 to 4.8 microg/kg/d for 7-14 days in 15 groups of six to eight dogs each in defined stages of natural or pharmacologically determined anestrus. Agonist treatment induced clinically and cytologically normal proestrus (in 89% of cases) within 4.8 +/- 0.2 x days, and resulted in behavioral estrus (71%), spontaneous late-proestrus LH (and FSH) surges, ovulation (59%) and pregnancy (44%) in a dose dependent manner. Outcomes of ovulation and pregnancy in most cases required that the dose be sufficiently large enough to routinely stimulate a large initial increase in LH and FSH (i.e., > or = 0.6 microg/kg/d), and of sufficient duration (i.e., > 7 days) to ensure that supra-basal gonadotropin levels persistedntil no longer needed for spontaneous continuation of an induced proestrus. Success additionally required that the GnRH dose be modest enough (i.e., < 1.8 microg/kg/d) to not excessively down-regulate spontaneous pre-ovulatory surge release of gonadotropin or be removed shortly before or at the time when the LH surges typically occurred (10-13 days after initiation of treatment). The 1.8 microg dose was compared to saline to assess the time course of its down-regulation action on serum LH in six ovariohysterectomized bitches compared to four saline-related controls. Results in intact bitches receiving the 1.8-microg doses demonstrated an LH-releasing effect for 10-11 days that overlapped a period of obvious down-regulation seen with the same dose after 3 days in the ovariohysterectomized bitches. In the latter, however, complete down-regulation to anestrus-like values did not occur until after 18-21 days of treatment. A dose of 0.6 microg/kg/d for 12 days yielded the best estrus-induction results, including pregnancy rates of 100% in six bitches treated in natural-anestrus bitches, six bitches in which anestrus had been advanced by a luteolytic prostaglandin treatment and in six bitches in which anestrus had been extended by progesterone implants administered for 3 months. Although lutrelin is not commercially available, these results provide guidelines for the development of estrus-inducing protocols with other GnRH-agonists of known biopotencies.
Department of Biological Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. pwc1@cornell.edu
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Concannon
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Temple
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Montanez
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Newton
D000780:Anestrus / Q000502:physiology; D000818:Animals; D004285:Dogs / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood; D004971:Estrus / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000031:analogs & derivatives* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood* / Q000378:metabolism; D008297:Male; D010062:Ovulation Induction / Q000379:methods / Q000662:veterinary*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects
D005300:Fertility Agents, Female; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; C030741:lutrelin acetate