Reproduction in Domestic Animals

158 J de Gier, NJ Beijerink, HS Kooistra and AC Okkensand fertilization (Kooistra et al. 1999a; de Gier et al.2006). Differential regulation of FSH and LH secretioncan at least partly be explained by the frequency andamplitude of GnRH pulses (Haisenleder et al. 1991;Vizcarra et al. 1997). In addition, gonadal feedback(Mann et al. 1992; Shupnik 1996) and a specific hypothalamicFSH-releasing factor (Yu et al. 1997) may playa role in the differential or non-parallel secretion of FSHand LH. Furthermore, the intracellular mechanisms forthe storage and release differ for FSH and LH (Chowdhuryand Steinberger 1975; Moyle and Campbell 1995;Nicol et al. 2004).In addition to a rise in hypothalamic GnRH release, anincrease in basal plasma FSH concentration, andincreased sensitivity of the pituitary and ovaries duringprogression of anoestrus, several other factors that maybe involved in the initiation of folliculogenesis andtermination of anoestrus have been reported. In somebitches, an increased LH pulsatility has been observedshortly before the start of pro-oestrus (Concannon et al.1986; Kooistra et al. 1999b; Tani et al. 1999; Beijerinket al. 2004). The exact role of increased LH pulsatility inthe termination of anoestrus in the bitch remains elusive.One of the main effects of the rising FSH level is theacquisition of LH receptors in the granulosa cells(Monniaux et al. 1997). It is therefore possible that theincrease in LH pulsatility at the end of anoestrus providesa stimulus to follicles which are no longer receptive toFSH but have acquired sufficient LH receptors.In addition, enhancement of the expression of thegenes encoding for the oestrogen receptor (Tani et al.1997) and P450 aromatase (which catalyses oestrogenbiosynthesis in the canine hypothalamus) during anoestrushas been reported in dogs (Inaba et al. 2002).However, although sporadic elevations are observed,plasma oestradiol concentrations are usually low duringanoestrus and do not begin to rise until approximately amonth before the LH peak (Jeffcoate 1993). Furthermore,there are no manifestations of oestrogen influenceson the reproductive tract or on sexual behaviourduring anoestrus, and vaginal endoscopy or cytologyreveals no evidence of oestrogenic stimulation until lateanoestrus.In addition, there is some evidence that factorscausing a decrease in opioidergic activity promote LHrelease and the termination of anoestrus (Concannon1993). Treatment with naloxone, an opioid antagonist,stimulated LH release at nearly all stages of the oestrouscycle (Concannon and Temple 1988). Finally, nochanges in the expression of the FSH receptor havebeen found during canine anoestrus (McBride et al.2001). This study demonstrated that anoestrus in bitchesis neither due to failure of expression of the canine FSHreceptor nor due to a change in splicing pattern to aninactive form.Dopaminergic influences and induction of a prematureoestrusIn addition to the earlier-mentioned changes in thehypothalamus-pituitary-ovary axis, there is evidence ofinvolvement of dopaminergic influences in the initiationof a new follicular phase in the bitch. Administration ofthe dopamine-agonists bromocriptine and cabergoline isassociated with both inhibition of prolactin release andshortening of the interoestrous interval (Okkens et al.1985; van Haaften et al. 1989; Concannon 1993; Onclinet al. 1995; Kooistra et al. 1999b; Verstegen et al. 1999;Gobello et al. 2002; Beijerink et al. 2003). If bromocriptinetreatment is started during the luteal phase,shortening of the interoestrous interval is primarily theresult of a shortening of the anoestrus (Okkens et al.1985), but is also due to shortening of the luteal phase(Okkens et al. 1985, 1990). The shortening of the lutealphase is probably caused by a decrease in the secretionof prolactin, the main luteotrophic factor in the bitch(Okkens et al. 1990; Onclin and Verstegen 1997).It has been hypothesized that the shortening of theanoestrus by dopamine-agonists is also the result of thesuppression of prolactin secretion, as prolactin mayinhibit gonadotrophin release. Indeed, it has beendemonstrated in various mammalian species that highcirculating levels of prolactin in different pathologicalsituations inhibit LH pulsatility (Sauder et al. 1984;Yazigi et al. 1997) or are associated with decreased LHsecretion (Park et al. 1993). In addition, decreasedplasma LH levels were observed during physiologicalhyperprolactinaemia in lactating sows, while lowering ofthe plasma prolactin concentration by bromocriptineadministration led to a rise in plasma LH levels in theseanimals (Bevers et al. 1983). Yet, under physiologicalconditions plasma prolactin concentrations are lowduring canine anoestrus (Olson et al. 1982; Kooistraand Okkens 2001), and no obvious changes in plasmaprolactin concentration have been observed during thetransition from anoestrus to the follicular phase in thebitch (Olson et al. 1982). Furthermore, anoestrus wasnot shortened in dogs treated with low dosages of theserotonin receptor antagonist metergoline (Okkens et al.1997), although the plasma prolactin levels were lowerthan in bromocriptine-treated dogs. The results of thelatter study suggest that the induction of the follicularphase is not initiated by suppression of prolactinsecretion. This raised the question whether administrationof a dopamine agonist in a dosage that is too low tosuppress prolactin secretion still will result in a shorteningof anoestrus in the bitch. To investigate thishypothesis, bitches were daily treated twice with 5(5-group), 20 (20-group), or 50 (50-group) microgramsof bromocriptine per kg body weight orally, starting28 days after ovulation (Beijerink et al. 2003). In thebitches receiving 5 lg bromocriptine per kg body weighttwice daily, there was no difference between the averageplasma prolactin concentration prior to and duringtreatment. This is in contrast with the bitches whichreceived 20 or 50 lg bromocriptine per kg body weighttwice daily, in which the average plasma prolactinconcentration prior to bromocriptine treatment wassignificantly higher than that during treatment. Themean ± SEM interoestrous interval was 136 ± 16 daysin the 5-group, 96 ± 6 days in the 20-group, and92 ± 11 days in the 50-group. Each of these intervalswas significantly shorter than the mean interoestrousinterval in control cycles, 216 ± 9 days. The meaninteroestrous intervals in the 20- and 50-groups weresimilar and significantly shorter than that of theÓ 2008 The Authors. Journal compilation Ó 2008 Blackwell Verlag