Search PubMed⌕ Search

Biomedical subjects

A C Okkens

Publications and source records attributed to A C Okkens.

At least 19 recordsLinked to original sources

Secretion of growth hormone and prolactin during progression of the luteal phase in healthy dogs: a review.

In some dogs the long exposure to high circulating progesterone levels during each oestrous cycle may result in a syndrome of growth hormone (GH) excess, i.e. acromegaly. The progesterone-induced GH production in dogs with acromegaly originates from the mammary gland. Also in healthy cyclic bitches, the pulsatile secretion pattern of GH changes during progression of the luteal phase, with basal GH secretion being higher and pulsatile GH secretion being lower when plasma progesterone concentration is high. This may be explained by partial suppression of pituitary GH release by progesterone-induced GH production in the mammary gland. Progesterone also modulates the secretion of prolactin in the bitch. In pregnant and overtly pseudopregnant bitches, the plasma prolactin concentration starts to rise about 1 month after ovulation, which is when the plasma progesterone concentration begins to decline. Also in healthy cyclic bitches, most prolactin is released during the second half of the luteal phase. The changes in GH and prolactin release during the luteal phase may promote the physiological proliferation and differentiation of mammary gland tissue in the bitch. In the early part of the luteal phase progesterone-induced mammary GH initiates proliferation of the mammary epithelium, whereas in the late luteal phase, when progesterone concentrations decrease, prolactin release increases and promotes lobuloalveolar differentiation.

Animals↗

Secretion of prolactin and growth hormone in relation to ovarian activity in the dog.

In pregnant bitches an apparent increase in plasma prolactin concentrations is observed during the second half of pregnancy, mean plasma prolactin concentrations peak on the day of parturition, fall for the next 24-48 h and then rise again. During lactation, high plasma prolactin concentrations are observed. Plasma prolactin levels in non-pregnant bitches appear to be lower than in pregnant animals, particularly in the last part of the luteal phase. Pulsatile secretion of prolactin has been observed during the luteal phase and mid-anoestrus. Progression of the luteal phase is found to be associated with an increase in prolactin release. The association of a strong increase of prolactin release and a decrease of plasma progesterone concentrations has also been demonstrated in overtly pseudopregnant bitches. Elevated prolactin secretion during progression of the luteal phase in the bitch may play a role in mammogenesis and is important because of the luteotrophic action of prolactin. Acromegaly is a syndrome of tissue overgrowth and insulin resistance due to excessive growth hormone (GH) production. In the bitch, acromegaly can be induced either by endogenous progesterone or by exogenous progestagens. Progestagen-induced GH production in this species originates from foci of hyperplastic ductular epithelium of the mammary gland. Pulsatile secretion of GH has been observed in normal cyclic bitches. In contrast with the pulsatile GH secretion seen in healthy dogs, the progestagen-induced plasma GH levels in bitches with acromegaly do not have a pulsatile secretion pattern. Just as with prolactin, the plasma progesterone levels influence the secretion pattern of GH in the bitch. The pulsatile secretion pattern of GH changes during the progression of the luteal phase in healthy cyclic bitches, with higher basal GH secretion and less GH being secreted in pulses during the first part of the luteal phase. The progesterone-induced GH production may promote the proliferation and differentiation of mammary gland tissue during the luteal phase of the bitch by local autocrine/paracrine effects and may exert endocrine effects.

Acromegaly↗

Role of changes in the pulsatile secretion pattern of FSH in initiation of ovarian folliculogenesis in bitches.

The results of two studies in which the pulsatile secretion patterns of LH and FSH were investigated in six Beagle bitches during early, mid- and late anoestrus and in six anoestrous Beagle bitches treated with bromocriptine are summarized to improve our knowledge of the endocrine changes that lead to a new follicular phase in bitches. Blood samples for the determination of secretory profiles were obtained via jugular venepuncture at 10 min intervals for 6 h. In untreated bitches, blood samples were collected during early, mid- and late anoestrus. In bromocriptine-treated bitches (20 micrograms kg-1 twice each day, starting 100 days after ovulation until the start of the next oestrous cycle), blood samples were collected before treatment and at 2 week intervals after the start of bromocriptine treatment until the next ovulation. In all bitches, FSH and LH were secreted in a pulsatile manner and FSH pulses coincided with LH pulses. Progression from early to late anoestrus was associated with an increase in FSH secretion without a concomitant increase in LH secretion. The bromocriptine-induced shortening of the interoestrous interval was also associated with an increase in FSH secretion without a concomitant increase in LH secretion. These results indicate that in bitches an increase in circulating FSH should be considered to be a critical event required for the initiation of ovarian folliculogenesis and consequently the termination of anoestrus.

Anestrus↗

Influence of litter size and breed on the duration of gestation in dogs.

The variation in the duration of gestation, defined as the period from mating to parturition, was studied in 113 bitches of six breeds (31 Dobermans, 31 Labrador retrievers, 14 German shepherds, 13 Bernese mountain dogs, 12 golden retrievers and 12 West Highland white terriers). The bitches were mated once on the optimal day for mating, which was established by measuring the plasma concentration of progesterone. The duration of gestation varied between 58 and 65 days with a mean of 61.4 +/- 1.5 days (+/- SD). The mean duration of gestation in West Highland white terriers (62.8 +/- 1.2 days) was significantly longer than that of German shepherds (60.4 +/- 1.7; P < 0.001), Labrador retrievers (60.9 +/- 1.5; P < 0.001) and Dobermans (61.4 +/- 1.0; P < 0.025). The variation in the duration of gestation in any one of the six breeds was low, ranging from 4 to 7 days, or less when litters of one pup (n = 4) were excluded. The number of pups per litter varied between one and 15 with a median of eight pups. In the total population, the duration of gestation was negatively correlated with litter size (r = -0.73; P = 0.005) for litters (n = 112) containing < or = 13 pups. However, within each breed multiple regression analysis failed to show any influence of litter size on the duration of gestation. The median litter size of different breeds and the mean duration of gestation were negatively correlated (r = -0.78; P = 0.03; n = 6). Therefore, although it was not conclusively proven, the results indicate that the breed is a major determinant of the duration of gestation in bitches and that the influence of breed may be ascribed to breed-related differences in litter size.

Animals↗

Termination of mid-gestation pregnancy in bitches with aglepristone, a progesterone receptor antagonist.

Six pregnancies were terminated in mid-gestation with aglépristone, a progesterone receptor antagonist, in 5 beagle bitches in order to determine the effects of aglépristone on plasma concentrations of prolactin and progesterone, the duration of the luteal phase, and the interestrous interval. In addition, the effects of aglépristone on the condition of the uterus and fetuses were examined by ultrasonography. After confirmation of pregnancy by ultrasonography, the dogs received 10 mg, s.c. aglépristone per kg body weight on 2 consecutive days at about 30 d post ovulation. Before, during and after treatment with aglépristone, plasma samples were collected for determination of the concentrations of prolactin and progesterone. The condition of the uterus and fetuses was assessed by ultrasonography the day before and at least 3 times a week for at least 2 wk after aglépristone administration. Termination of pregnancy occurred within 4 to 7 d after the start of aglépristone treatment, which was well tolerated, with no side-effects except slight vaginal discharge. The results of ultrasonographic examination indicated that aglépristone leads to abortion but not to fetal resorption. Elevated plasma concentrations of prolactin were observed during aglépristone treatment, while plasma progesterone levels remained unchanged. Pregnancy termination with aglépristone resulted in premature cessation of luteal function. In addition, the interestrous interval was shortened. The latter effects may be the consequence of actions of the progesterone receptor antagonist at the hypothalamus-pituitary level. In conclusion, aglépristone proved to be a safe and effective abortifacient in mid-gestation in the bitch. The results of the present study also indicated that aglépristone directly or indirectly influences pituitary function.

Abortifacient Agents↗

[Plasma prolactin concentration and the effect of metergoline in pseudopregnant Afghan hounds].

The effects of metergoline, a 5-hydroxytryptamine (serotinin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-psueodopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentration of prolactine in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

Animals↗

Pulsatile secretion pattern of growth hormone during the luteal phase and mid-anoestrus in beagle bitches.

The pulsatile secretion pattern of growth hormone was investigated during four stages of the luteal phase and during mid-anoestrus in six cyclic beagle bitches. Plasma samples were obtained via jugular venepuncture at 10 min intervals for 12 h at 19 +/- 2 (mean +/- SEM; luteal phase 1), 38 +/- 2 (luteal phase 2), 57 +/- 2 (luteal phase 3), 78 +/- 2 (luteal phase 4) and 142 +/- 4 days (mid-anoestrus) after ovulation. During all stages, growth hormone was secreted in a pulsatile fashion. The mean basal plasma growth hormone concentration during luteal phase 1 (2.2 +/- 0.3 microgram l(-1)) was significantly higher than that during luteal phase 4 (1.5 +/- 0.1 microgram l(-1)) and mid-anoestrus (1.4 +/- 0.2 microgram l(-1)). The mean area under the curve (AUC) above zero during luteal phase 1 (27.3 +/- 2.7 microgram l(-1) in 12 h) tended to be higher than that during luteal phase 4 (20.8 +/- 1.8 microgram l(-1) in 12 h) and mid-anoestrus (19.2 +/- 2.5 microgram l(-1) in 12 h). In contrast, the mean AUCs above the baseline during luteal phase 1 (1.1 +/- 0.5 microgram l(-1) in 12 h) and luteal phase 2 (1.2 +/- 0.5 microgram l(-1) in 12 h) were significantly lower than that during luteal phase 4 (2.8 +/- 0.5 microgram l(-1) in 12 h). In conclusion, the pulsatile secretion pattern of growth hormone changes during the luteal phase in healthy cyclic bitches: basal growth hormone secretion is higher and less growth hormone is secreted in pulses during stages in which the plasma progesterone concentration is high. It is hypothesized that this change is caused by a partial suppression of pituitary growth hormone release by progesterone-induced growth hormone production in the mammary gland. The progesterone-induced production of growth hormone in the mammary gland may promote the physiological proliferation and differentiation of mammary gland tissue during the luteal phase of the bitch by local autocrine-paracrine effects. In addition, progesterone-induced mammary growth hormone production may exert endocrine effects, such as hyperplastic changes in the uterine epithelium and insulin resistance.

Anestrus↗

Concurrent pulsatile secretion of luteinizing hormone and follicle-stimulating hormone during different phases of the estrous cycle and anestrus in beagle bitches.

The 6-h secretory profiles of LH and FSH and the possible concordance between the episodic release of LH and FSH were studied in 6 beagle bitches during early, mid-, and late anestrus and during the follicular and luteal phases of the estrous cycle. Plasma samples were obtained at 10-min intervals via jugular venipuncture. In all stages of anestrus and in the luteal phase, FSH and LH secretion was pulsatile. All FSH pulses coincided with LH pulses. However, the mean duration of the FSH pulse (115 min) was significantly longer than that of the LH pulse (72 min). The basal plasma LH concentration was low compared with the maximum peak levels, whereas FSH pulses were characterized by relatively low peaks compared with the basal levels. In contrast to the basal plasma LH levels and the area under the curve (AUC) for LH, the basal plasma FSH levels and the AUC for FSH increased significantly as anestrus progressed. During the follicular phase, the secretory pattern of LH was characterized by frequent increases of short duration. During this phase, the basal plasma FSH concentration was relatively low, whereas the basal plasma LH level was high in comparison with that in the other phases of the estrous cycle. The luteal phase was characterized by an increased frequency of LH pulses, a shorter duration of the LH peaks, and a tendency to a lower amplitude of both LH and FSH peaks compared with values observed during anestrus. It is concluded that in the bitch, FSH and LH pulses are released in concordance and that progression from early to late anestrus is associated with an increase in basal plasma FSH concentration without a concomitant rise in basal plasma LH concentrations. The latter suggests that in the bitch an increase in circulating FSH should be considered to be a critical event required for the initiation of ovarian folliculogenesis and consequently for the termination of anestrus.

Anestrus↗

Bromocriptine-induced premature oestrus is associated with changes in the pulsatile secretion pattern of follicle-stimulating hormone in beagle bitches.

The secretory profiles of LH and FSH were investigated before and during the administration of bromocriptine in six beagle bitches. Plasma samples were obtained via jugular venepuncture at 10 min intervals for 6 h every 2 weeks until the next ovulation. Bromocriptine treatment was started 100 days after ovulation. Both before and after bromocriptine treatment, LH and FSH pulses occurred together. The mean duration of the FSH pulse (120 min) was significantly longer than that of the LH pulse (80 min). The interoestrous interval in the bitches treated with bromocriptine was significantly shorter than that of the preceding cycle (160 +/- 3 versus 206 +/- 24 days). The mean basal plasma FSH concentration (7.4 +/- 0.6 versus 6.1 +/- 0.7 iu l-1) and the mean area under the curve for FSH (46.6 +/- 4.7 versus 40.4 +/- 4.4 iu l-1 in 6 h) increased significantly after the start of the bromocriptine treatment. In contrast, the differences in mean basal plasma LH concentration (2.1 +/- 0.2 versus 2.0 +/- 0.2 micrograms l-1) and the mean area under the curve for LH (19.0 +/- 3.1 versus 19.5 +/- 2.5 micrograms l-1 in 6 h) between the day before and 14 days after the start of the bromocriptine treatment were not significant. Bromocriptine administration also lowered the mean amplitude of the FSH pulse and shortened the mean duration of the FSH pulse, without influencing the LH pulse. In addition to demonstrating the concurrent pulsatile secretion of LH and FSH, the results of the present study demonstrate that the bromocriptine-induced shortening of the interoestrous interval in the bitch is associated with an increase in plasma FSH concentration without a concomitant increase in plasma LH concentration. This finding indicates that treatment with the dopamine agonist bromocriptine increase plasma FSH to a concentration that results in the enhancement of follicle development.

Analysis of Variance↗

Incidence of patent Toxocara canis infection in bitches during the oestrous cycle.

The incidence of patent Toxocara canis infection as result of reactivation of somatic larvae with subsequent tracheal migration was investigated by faecal examination during 23 oestrous cycles of 15 bitches. Blood samples were collected for determination of total and differential leukocyte counts, prolactin concentration, and Toxocara titre. Five pregnant dogs were used as controls. In the cyclic dogs there were no alterations in white blood cell counts or prolactin concentration, in contrast with the pregnant dogs, in which both variables increased, starting 10 days after onset of the luteal phase. The difference was significant at day 40 and day 60 (both p < 0.005). No significant differences were observed in the number of eosinophils or in the Toxocara antibody titre. T. canis eggs were only found in the faeces of three 1-year-old, cyclic dogs at 1, 60, and 140 days, respectively, after the onset of the luteal phase. It is concluded that cyclic beagle bitches, in which prolactin levels increase in the second half of the luteal phase, are unlikely to be at higher risk for patent T. canis infection than in other phases.

Animals↗

Dopamine agonistic effects as opposed to prolactin concentrations in plasma as the influencing factor on the duration of anoestrus in bitches.

The duration of the interoestrous interval and plasma concentrations of prolactin were determined in seven bitches treated with 0.1 mg metergoline kg-1 body mass orally, twice a day during anoestrus to determine whether shortening of the interoestrous interval in dogs is due to suppression of prolactin secretion. The results were compared with those of a previous experiment in which four bitches were treated with 20 micrograms bromocriptine kg-1 body mass orally during the luteal period and anoestrus. The interoestrous interval of the dogs treated with metergoline, 240 +/- 67 days, was similar to the interoestrous interval before treatment, 225 +/- 54 days. However in the dogs treated with bromocriptine, the interoestrous interval was shortened to 123 +/- 46 days. The average of the means of the plasma concentrations of prolactin during metergoline treatment, 1.5 +/- 0.5 micrograms l-1, was lower (P = 0.03) than the average of the means of the plasma concentrations of prolactin during the 2 weeks before treatment, 3.6 +/- 2.3 micrograms l-1, but did not differ from the average of the means of the plasma concentrations of prolactin, 2.1 +/- 0.5 micrograms l-1, of the dogs treated with bromocriptine during anoestrus. As the plasma concentrations of prolactin were similar during metergoline and bromocriptine treatment, and the anoestrous period was shortened during bromocriptine treatment, but not during metergoline treatment, these results suggest that the induction of oestrus by dopamine agonists is not initiated by suppression of prolactin secretion, but by other direct or indirect dopaminergic effects.

Anestrus↗

Comparison of long-term effects of ovariectomy versus ovariohysterectomy in bitches.

Although ovariectomy is less invasive and less time-consuming than ovariohysterectomy, most surgical textbooks recommend ovariohysterectomy for routine neutering of bitches. This advice is probably based on concerns about the development of uterine disease after ovariectomy. However, there is no evidence that conditions such as cystic endometrial hyperplasia (CEH)-endometritis develop in the ovariectomized bitch, unless progestagens are administered. The purpose of this study was therefore to compare the long-term effects of ovariectomy and ovariohysterectomy, including the incidence of urinary incontinence. Questionnaires were sent to 264 owners of bitches, in which ovariectomy (126) or ovariohysterectomy (138) had been performed as a routine neutering procedure 8-11 years earlier. Complete data were available for 69 bitches of the ovariectomy group and for 66 bitches from the ovariohysterectomy group. There were no indications that endometritis had developed in bitches of the ovariectomy group. None of the bitches was sexually attractive to male dogs after neutering. The occurrence of a clear to white vaginal discharge was reported in two bitches of each group, but none of these four bitches appeared to be ill during the periods when the discharge was present. Furthermore, with the exception of urinary incontinence, no problems were reported that could be related to the surgical neutering. Six of the ovariectomized bitches and nine of the ovariohysterectomized bitches eventually developed urinary incontinence. Of these 15 bitches (11%), 12 weighed more than 20 kg. Bouvier des Flandres bitches were at a higher risk of developing urinary incontinence than were those of the other breeds. The possibility that the urinary incontinence was due at least in part to other conditions must be considered, since eight of the bitches were 9 years or older before urinary incontinence occurred and seven of the incontinent bitches also had polyuria or polydipsia. There were no significant differences in the incidence of urogenital problems listed above between the bitches of the ovariectomy and ovariohysterectomy group. It is hypothesized that a uterine disease such as CEH-endometritis cannot develop after complete ovariectomy, unless progestagens are administered. The results of this study indicate that ovariectomy does not increase the risk of CEH-endometritis or other complications in comparison with ovariohysterectomy. It is concluded that there is no indication for removing the uterus during routine neutering in healthy bitches. On the contrary, ovariectomy should be considered the procedure of choice.

Animals↗

Plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and the effect of metergoline.

The effect of metergoline, a 5-hydroxytryptamine (serotonin) antagonist, on the plasma concentrations of prolactin in overtly pseudopregnant Afghan hounds and on the clinical symptoms of overt pseudopregnancy were studied. Plasma concentrations of prolactin and progesterone were determined in six Afghan hounds with signs of overt pseudopregnancy for 2-3 weeks and in three Afghan hounds that were not pseudopregnant at the time of blood sampling. In the overtly pseudopregnant bitches the plasma concentrations of prolactin before treatment (35.5 +/- 8.5 micrograms l-1) were significantly higher than the plasma concentrations of prolactin of the three bitches that were not pseudopregnant (6.3 +/- 0.5 micrograms l-1); the latter values were similar to those of non-pseudopregnant beagle bitches during the total luteal phase. The six pseudopregnant Afghan hounds were treated for 10 days with the antiserotoninergic drug metergoline. At 2 h after the onset of treatment with metergoline, the mean plasma concentration of prolactin had decreased to 10.8 +/- 2.9 micrograms l-1. The plasma concentrations of prolactin continued to decline to 5.4 +/- 1.0 micrograms l-1 at 4 h and to 1.0 +/- 0.1 microgram l-1 during treatment days 3-10. Signs of pseudopregnancy, such as swelling of the mammary glands and digging, decreased during the treatment period. The treatment was associated with mild behavioural side effects such as whimpering and aggressiveness. These side effects are probably not related to suppression of prolactin but are due to a direct effect on serotoninergic pathways in the brain. It is concluded that high plasma concentrations of prolactin are associated with the development and maintenance of pseudopregnancy. The serotonin antagonist metergoline strongly suppresses plasma concentrations of prolactin in pseudopregnant dogs and decreases the clinical signs of pseudopregnancy.

Animals↗

Lack of association of progestin-induced cystic endometrial hyperplasia with GH gene expression in the canine uterus.

Growth hormone (GH) is produced in progestin-induced hyperplastic ductular mammary epithelia in dogs. Progestins also induce the development of cystic endometrial hyperplasia (CEH) in this species. The study reported here investigated whether GH gene expression could also be demonstrated in progestin-induced hyperplastic epithelium in the canine uterus. Eight beagle bitches were treated with 10 mg medroxyprogesterone acetate (MPA) kg-1 body mass s.c. at intervals of 3 weeks, for a total of five times in four dogs (group I) and for a total of 13 times in the other four dogs (group II). Blood samples were collected twice during each 3 week period for measurement of plasma concentrations of GH, insulin-like growth factor I (IGF-I) and IGF-II. At the end of the series of injections uterine tissue was obtained by ovario-hysterectomy. Histological examination confirmed that CEH was present in all uteri after MPA treatment; the changes in the dogs of group I were less marked than those in group II. Immunohistochemical examination of the uterine tissues showed that immunoreactive(i) GH was present in a number of uteri with CEH. iGH was usually located in the cytoplasm of glandular epithelial cells. However, reverse transcriptase PCR using GH-specific primers failed to demonstrate mRNA encoding GH in the uterine tissue of all dogs. It is concluded that local production of GH is not involved in progestin-induced hyperplasia of uterine epithelial cells in dogs.

Animals↗

Growth hormone concentrations in mammary secretions and plasma of the periparturient bitch and in plasma of the neonate.

The presence of growth hormone (GH) in mammary secretions of bitches was investigated in relation to plasma GH concentrations at about the time of parturition and during the first weeks of lactation. Plasma GH concentrations in neonates were measured during the first weeks of lactation, to determine whether GH in maternal milk contributes to plasma concentrations of GH in the neonate. Gastrointestinal uptake of GH was studied by measurement of plasma bovine GH (bGH) concentrations after intragastric administration of bGH. High concentrations of GH were found in the mammary secretions of the bitches, particularly before parturition and in colostrum, exceeding maternal plasma concentration up to 100-1000 times. GH concentrations in milk were not not significantly correlated with GH concentrations in plasma of bitches or neonates. Bovine GH could not be detected in neonatal plasma for 4 h after intragastric administration of bGH. The presence of high concentrations of canine GH (cGH) in ante-partum and colostral mammary secretions is consistent with the progesterone-induced mammary biosynthesis of GH. GH in milk is probably not absorbed from the gastrointestinal tract into the blood circulation of the newborn in its intact form.

Animals↗

Increasing sensitivity of the pituitary to GnRH from early to late anoestrus in the beagle bitch.

The sensitivity of the pituitary to GnRH in early and late anoestrus and the indirect response of the ovary were investigated in six adult beagle bitches. Plasma concentrations of LH and oestradiol were determined after i.v. injection of graded doses of GnRH (0, 0.01, 0.1, 1, 10 and 100 micrograms kg-1). The responses were measured by the LH and oestradiol concentration profiles over time. The responses of LH and oestradiol were significantly dose dependent (P = 0.002 and P < 0.001, respectively). The responses of LH and oestradiol were significantly higher (P = 0.02 and P = 0.001, respectively) in late anoestrus than in early anoestrus. The responses of LH and the responses of oestradiol were positively correlated (r = 0.97, P = 0.001). It is concluded that during the course of anoestrus in the bitch pituitary sensitivity to GnRH increases while the ovary responds accordingly.

Anestrus↗