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 × GnRH, and at six different doses from 0.2 to 4.8 μg/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 × 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., ≥0.6 μg/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 μg/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 μg 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-μg 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 μg/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.