Induction of estrus in bitches with normal and persistent anestrus using human menopausal gonadotropin (hMG)

Human menopausal gonadotropin (hMG) was administered intramuscularly to 10 bitches during apparently normal anestrus (n = 7) or persistent anestrus (n = 3). Each dog received a 75-IU dose of hMG (75 IU LH and 75 IU FSH; 1 to 7 units/kg) daily for nine days. Nine bitches responded with obvious signs of proestrus within 3 to 9 days. Of these, 3 bitches exhibited a weak proestrus while 2 exhibited a normal estrus and ovulation but failed to become pregnant The remaining 4 bitches became pregnant at the induced cycle and produced normal litters at 72 to 85 d after the start of treatment, including 1 bitch that had been treated at 24 mo after the last estrus. In 2 cases, treatment resulted in ovulation following 25 or 34 mo of chronic pubertal anestrus, 1 of which became pregnant. The results suggest that hMG can be a useful gonadotropin preparation for inducing estrus in dogs.     

Effect of stage of anestrus on the induction of estrus by the dopamine agonist cabergoline in dogs

Beagle bitches were administered the dopamine D2 receptor agonist cabergoline in 3 groups of 5 animals each, starting on known days of the estrous cycle. Cabergoline treatment was started in either early anestrus (Days 93 to 108), mid-anestrus (Days 123 to 156), or late anestrus (Days 161 to 192) at doses of 5 ug/kg/d, per os, and was continued until the confirmation of induced proestrus or for 40 d. Reproductive parameters were compared with those in 5 control anestrous bitches (Days 90 to 150). In control bitches, the mean (+/- SEM) interval to the next proestrus (73+/-11 d) resulted in an interestrus interval (192+/-9 d) similar to that of the previous cycles (196+/-11 d). In 14 of the 15 cabergoline-treated bitches, the next proestrus occurred within 4 to 30 d, was premature in early and mid-anestrous bitches and developed with low variability within groups. The resulting intervals to proestrus in bitches treated with cabergoline in early anestrus (20+/-2 d), mid-anestrus (14+/-3 d) and late anestrus (6+/-1 d) resulted in interestrus intervals in those groups of 131+/-5, 166+/-7 and 196+/-2 d, respectively. In response to treatment, interestrus intervals were reduced (P<0.05) and more synchronous (P<0.05) in early and mid-anestrus bitches, and were more synchronous (P<0.05) in late-anestrous bitches compared with those of control bitches or those of the previous cycle. Periovulatory estradiol and progesterone profiles of induced cycles in treated bitches were similar to those of spontaneous cycles in control bitches. Four of 5 control bitches and 12 of the 14 responding cabergoline-treated bitches became pregnant and produced normal litters. Plasma prolactin concentrations at Days 2 and 5 of treatment (0.3+/-0.1 ng/mL) and at the onset of proestrus shortly before the end of treatment (0.4+/-0.1 ng/mL) were lower (P<0.05) than those present in anestrus prior to treatment (1.7+/-0.6 ng/mL) or in control bitches. Prolactin was also low at the onset of proestrus in control bitches (0.5+/-0.2 ng/mL). The results demonstrate that prolactin-lowering doses of the dopamine agonist cabergoline can terminate the normal obligate anestrus in dogs, and that the effect occurs more slowly in early anestrus than in mid or late anestrus.     

The effects of a low dose of cabergoline on induction of estrus and pregnancy rates in anestrous bitches

This is the first report of successful induction of normal estrus and ovulation in breeder bitches with as a low dose as 0.6 microg/kg/day of cabergoline formulation marketed for use in women. Sixty-one pure breed bitches from various breeds were used in the study at their already determined periods of anestrus. Twenty-four dogs formed the control group, while 37 bitches were administered with two different doses of cabergoline (recommended dose group, n=10, 5 microg/kg/day and low dose group, n=27, 0.6 microg/kg/day). Induced estrus rates and mean treatment and proestrus durations of dogs in these two dose groups were compared. At the second phase of the study, the effects of 500 IU human chorionic gonadotropin (hCG) administered on days 1 and 3 of estrus induced by the low dose of cabergoline, on the duration of behavioral estrus, ovulation rates, pregnancy rates and the number of offspring were investigated. For this purpose, the dogs with signs of proestrus (22/27) following the treatment in the low dose group were assigned into two subgroups. Five hundred IU of hCG (Pregnyl, Organon, Turkey) was intramuscularly administered to eight of these dogs [low dose (hCG+) group] on days 1 and 3 of estrus. The remaining 14 dogs were not treated with hCG [low dose (hCG-) group]. An aqueous solution of cabergoline (Dostinex, Pharmacia, Italy) was orally administered until 2 day after the onset of proestrus or for a maximum of 42 days. Blood samples were taken daily from all treatment and 11 control bitches during the first five days of behavioral estrus to measure progesterone concentrations. In the recommended dose and low dose groups, estrus was induced between days 8-45 and 4-48 (mean: 23.63+/-14.33 and 24.41+/-14.31 days), in the ratio of 80.0 and 81.5%, respectively (p>0.05). In both dose groups, post-treatment interestrous intervals were significantly shorter than both those of the control group and their own pre-treatment interestrous intervals (p<0.05). Ovulation rates, pregnancy rates and mean number of offspring delivered by the dogs in the recommended dose, low dose (hCG-), low dose (hCG+) and control groups were found to be similar (p>0.05). However, the mean duration of behavioral estrus of the dogs in the low dose (hCG+) group was found to be significantly longer compared to dogs in all other groups (p<0.05). In both dose groups, no correlation could be found between the anestrus stages and treatment durations (p>0.05). Shortly, it has been concluded from the study that (1) normal and fertile estrus can be induced more economically in bitches during different stages of anestrus using as a low dose of 0.6 microg/kg of cabergoline formulation marketed for use in women, and that (2) hCG injections on days 1 and 3 of the estrus induced by this method has no positive effects on the ovulation rates, pregnancy rates and the number of offspring per pregnancy.     

Increased LH pulse frequency and estrogen secretion associated with termination of anestrus followed by enhancement of uterine estrogen receptor gene expression in the beagle bitch

The relationships among pulsatile LH secretion pattern, estrogen secretion, and expression of the uterine estrogen receptor gene were examined throughout the estrous cycle in beagle bitches. In Experiment 1, blood samples were collected from 30 bitches every 10 min for 8 h from a cephalic vein during different phases of the estrous cycle. An increase in the mean plasma levels of LH occurred from mid to late anestrus (P < 0.01). The LH pulse frequency increased (P < 0.01) from late anestrus to proestrus, and was strongly correlated (r = 0.96, P < 0.001) with the mean plasma level of estradiol-17 beta (E2). In Experiment 2, middle uterine samples, including the myometrium and endometrium, from 18 bitches were taken at 6 stages of the estrous cycle. The total number of estrogen receptors and nuclear estrogen receptor and its mRNA levels in the uterus also increased (P < 0.01) from late anestrus to proestrus. Mean plasma E2 level and the number of uterine estrogen receptor were positively correlated (r = 0.81, P < 0.05). In Experiment 3, nine bitches were ovariectomized in mid anestrus. Two weeks later they received a single injection of 10 or 50 micrograms/kg, i.m., estradiol benzoate. The number of uterine estrogen receptor and their mRNA levels for ovariectomized bitches were low, but increased (P < 0.05) after treatment with a low dose of estradiol benzoate. These results suggest that increases in LH pulse frequency and estrogen secretion are associated with termination of anestrus and that subsequent enhancement of uterine estrogen receptor expression may be up-regulated by estradiol.     

Differential regulation of the secretion of luteinizing hormone and follicle-stimulating hormone around the time of ovulation in the bitch

Plasma concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were determined 3-6 times daily in six Beagle bitches from the start of the follicular phase until 5 d after the estimated day of ovulation. The aim of the study was to gain more detailed information regarding the changes in and the temporal relation between these hormones around the time of ovulation. In all bitches, the pre-ovulatory LH surge was accompanied by a pre-ovulatory FSH surge. The mean duration of the pre-ovulatory FSH surge (110 +/- 8 h) was significantly longer than that of the pre-ovulatory LH surge (36 +/- 5 h). The FSH surge started concomitantly with the pre-ovulatory LH surge in four bitches, and 12 h before the start of the LH surge in the other two bitches. The pre-ovulatory LH surge had a bifurcated pattern in four bitches. The mean plasma LH concentration before (1.9 +/- 0.4 microg/L) and after (1.9 +/- 0.3 microg/L) the pre-ovulatory LH surge were similar. The mean plasma FSH concentration during the period 72-28 h before the pre-ovulatory LH surge (1.6 +/- 0.3 U/L) was lower (P < 0.001) than that during the period 100-144 h after the pre-ovulatory LH surge (3.1 +/- 0.2U/L). In conclusion, this study demonstrated concurrent pre-ovulatory surges of FSH and LH and provided more evidence for differential regulation of the secretion of FSH and LH.     

The induction of parturition in the bitch using sodium cloprostenol

The objectives of this studies were to determine a continuous low-dose treatment regimen for the administration of sodium cloprostenol to the bitch that did not cause polydipsia, and whether this treatment would induce normal and timed parturition in bitches during late pregnancy. Non-pregnant greyhound bitches (n=18) received sodium cloprostenol subcutaneously, via a miniosmotic pump, at dose rates of 0.875 to 4.5 microg/kg/24 h, for 7 days (Days 0 to 7). Daily water intake was measured from Day -2 to Day 9. Polydipsia was observed in bitches treated with the higher dose rates but not in bitches treated with the lowest dose rate of 0.875 microg/kg/24 h. In the second experiment, pregnant greyhound bitches received sodium cloprostenol at dose rates of 1 (n=4), 2 (n=1) and 3 microg/kg/24 h (n=1), on Day 57 of pregnancy. Polydipsia was observed in bitches treated at the higher dose rates of 2 and 3 microg/kg/24 h, but not in the bitches treated at the lower dose rate of 1 microg/kg/24 h. These treatments resulted in the successful induction of parturition. Parturition was associated with a decrease in plasma progesterone concentrations, a reduction in body temperature, and an increase in plasma concentrations of 13,14-dihydro-15-keto prostaglandin F2alpha. The first puppy was born 37.7 +/- 2.9 h after the start of treatment (range 28 to 46 h). The duration of whelping was approximately 15.7 +/- 2.2 h (range 10 to 24 h). The litter size was 9.2 +/- 0.8 pups (range 6 to 12 pups), and the puppy survival rate was 6.0 +/- 0.8 per litter (range 4 to 9 pups). This study demonstrated that the administration of sodium cloprostenol in continuous low dose for 24 h is an effective treatment for the induction of parturition in bitches during late pregnancy. This treatment resulted in the birth of healthy pups, with minimal or no side effects to the bitch.     

Estrus induction in the bitch using a combination diethylstilbestrol and FSH-P

The purpose of the study was to induce estrus and ovulation in normal bitches using a combination of diethylstilbestrol (DES) and follicle stimulating hormone of porcine pituitary origin (FSH-P). Thirteen mature mongrel female dogs were divided into two groups, the first group was treated for estrus induction during late anestrus and the second group during mid-anestrus. The dogs were monitored by teasing, vaginal cytology, and hormonal assay during the induced (n = 13) and the previous spontaneous estrous cycle (n = 9). Six of eight and three of five bitches came into standing estrus in the first and second group, respectively. Of the bitches that came into estrus, three conceived in the first group and one in the second. The average induced litter size was 7.0 versus 7.5 for the colony. Based on vaginal cytology the induced proestrus and estrus lasted 1.7 (0 to 3) and 12.9 (4 to 24) d, respectively, while the spontaneous proestrus and estrus lasted 5.8 (0-17) and 12.8 (9-15) d, respectively. Progesterone profiles were similar between the induced and spontaneous estrous cycles, although the progesterone peak was higher during the spontaneous cycle. The preovulatory luteinizing hormone (LH) surge was observed in only one induced estrous cycle. Modest results were obtained with this therapy. However, the litter sizes were normal and the induced cycles were very similar to the physiologic ones. No side effects were seen with the oral form of DES.     

Temporal relations between plasma concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol-17beta, progesterone, prolactin, and alpha-melanocyte-stimulating hormone during the follicular, ovulatory, and early luteal phase in the bitch

Compared with other domestic animals, relatively little is known about the changes in, and temporal relations between, reproductive hormones around the time of ovulation in the domestic bitch. Therefore, plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol-17beta, progesterone, prolactin (PRL), and alpha-melanocyte-stimulating hormone (alpha-MSH) were determined one to six times daily from the start of the follicular phase until 5 days after the estimated day of ovulation in six Beagle bitches. In all bitches, the pre-ovulatory LH surge was accompanied by a pre-ovulatory FSH surge. A pre-ovulatory PRL or alpha-MSH surge was not observed. The pre-ovulatory FSH and LH surges started concomitantly in four bitches, but in two bitches the FSH surge started 12 h earlier than the LH surge. The FSH surge (110+/-8 h) lasted significantly longer than the LH surge (36+/-5 h). In contrast with the pre-ovulatory FSH surge, the pre-ovulatory LH surge was bifurcated in four of six bitches. The mean plasma LH concentrations before (1.9+/-0.4 microg/L) and after (1.9+/-0.3 microg/L) the LH surge were similar, but the mean plasma FSH concentration before the FSH surge (1.6+/-0.3 U/L) was significantly lower than that after the FSH surge (3.1+/-0.2 U/L). In most bitches the highest plasma estradiol-17beta concentration coincided with or followed the start of the pre-ovulatory LH surge. In five of the six bitches the plasma progesterone concentration started to rise just before or concurrently with the start of the LH surge. In conclusion, the results of this study provide evidence for the differential regulation of the secretion of LH and FSH in the bitch. In addition, the interrelationship of the plasma profiles of estradiol-17beta and LH suggests a positive feedback effect of estradiol-17beta on LH surge release. The start of the pre-ovulatory LH surge is associated with an increase in the plasma progesterone concentration in this species.     

Levels of lutenizing hormone, estradiol and progesterone in serum during the estrous cycle and pregnancy in the beagle bitch (38491).

Levels of luteinizing hormone (LH), estradiol-17 beta and progesterone were determined by specific radioimmunoassays in sera obtained from Beagle bitches during proestrus, estrus and diestrus. Concentrations of LH (expressed as NIH-LH-SI equivalents) were 2.8 plus or minus 0.1 ng/ml in proestrus, 35.5 plus or minus 10.0 ng/ml during early estrus and 2.2 plus or minus 0.1 ng/ml in early diestrus. Peak levels of estradiol-17beta (68.9 plus or minus 11.0 ng/ml) were detected 24 hr prior to the LH peak, declined rapidly and reached basal levels (17.8 plus or minus 6.3 ng/ml) by five days following the LH peak. Levels of progesterone were 1.7 plus or minus 0.3 ng/ml during proestrus, 3.5 plus or minus 0.3 ng/ml during early estrus and 23.3 plus or minus 2.8 ng/ml on day 5 after the LH peak . Progesterone levels remained elevated through day 28 of diestrus and pregnancy. A significant decrease (p smaller than 0.05) in levels of prosgesterone occurred between day 28 of pregnancy and one day prior to shelping (3.3 plus or minus 1.2 ng/ml, with a further decrease on the day of whelping (1.1 plus or minus 0.2 ng/ml). Levels of estradiol-17beta and LH did not change significantly (p smaller than 0.0k) during diestrus or pregnancy.     

Effects of reproductive state on concentrations of thyroxine, 3,5,3'-triiodothyronine and cortisol in serum of dogs

Reproductive state of animals frequently is overlooked when examining endocrine functions of the thyroid gland and adrenal cortex. This experiment was done to determine effects of reproductive state on basal and stimulated concentrations of thyroxine (total T4), 3,5,3'-triiodothyronine (total T3) and cortisol in serum of adult Beagle dogs. Five male, 5 anestrous, 5 proestrous, 5 diestrous, 5 pregnant and 5 lactating dogs were fasted for 18 h before each dog received 5 IU of thyrotropic hormone (TSH) i.v. and 2.2 IU/kg of body weight of adrenocorticotropic hormone (ACTH) i.m. Blood samples were collected via jugular cannulas or by jugular venipuncture at 60, 45, 30, 15 and 1 min before and 0.5, 1, 2, 3, 4, 5, 8, 12 and 24 h after injection. Concentrations of T4 were similar in serum from diestrous and pregnant bitches but were greater (P less than 0.025) than those in dogs of other reproductive states before and after treatment with TSH. Concentrations of T3 were greater (P less than 0.005) in serum from diestrous bitches before and after TSH injection than in serum from dogs of all other reproductive states. Concentrations of T3 in males, anestrus, proestrus, pregnancy and lactation did not differ. Basal concentrations of cortisol did not differ consistently among reproductive states. However, concentrations post-ACTH were different (P less than 0.05) with anestrus = diestrus greater than lactation = pregnancy = male greater than proestrus. These results indicate that reproductive state of experimental animals must be considered when studying thyroidal and adrenal functions.     

Reproductive cycles of the domestic bitch

Domestic dogs are monoestrous, typically non-seasonal, polytocous, spontaneous ovulators and have a spontaneous luteal phase slightly longer (by approx 5 day) than the 64±1day luteal phases of a 65±1day pregnancy, a phase followed by an obligate anestrus before the next 2-3 week "heat" (proestrus-estrus). The resulting inter-estrus intervals of 5-12 months are variable among bitches, commonly 6-7 months, and range from highly variable to regular (to perhaps within±5-10 day of sequential 7 month cycle, for instance) within bitches, and across studies and do not vary significantly between pregnant and non-pregnant cycles. Hormone levels reported are those observed in this laboratory using previously reported assays and canine gonadotropin standards unless stated otherwise. Endocrine sequences for dog cycles are not unlike those of many other mammals, including selection of ovulatory follicles by increased LH pulsatility, the occurrence of estrus behavior and LH surge during a decline in the estrogen: progestin ratio, a pronounced preovulatory luteinization as in humans and rodents, and luteotrophic roles for both LH and prolactin. Non-pregnant bitches have a spontaneously prolonged luteal phase, often longer and with a more protracted decline in serum progesterone than in pregnancy as there is no uterine luteolytic mechanism. The obligate anestrus of 8-40 weeks is terminated by poorly understood interactions of environment (e.g. pheromones, possibly photoperiod) and a potential endogenous circannual cycle in sensitivities of hypothalamic dopaminergic, serotonergic and/or opioid pathways.     

Effects of morphine and naloxone on serum LH, FSH and prolactin levels and on hypothalamic content of LH-RF in proestrous rats.

Proestrus surges of serum LH, FSH and prolactin (PRL) were significantly reduced when morphine HCl (50 and 10 mg/kg) was administered to 4-day cycling rats just prior to the proestrous critical period. The inhibitory effect of morphine was reversed by naloxone, a morphine antagonist, at the dose which had no effect on the proestrus surges of serum LH, FSH or PRL. The hypothalamic LH-RF content of proestrous rats at 1800 hr (during the proestrus surge) was not significantly different from that at 1400 hr (before the surge) and was not affected by pretreatment with morphine or naloxone. Our results suggest that naloxone reverses the anti-ovulatory effect of morphine by antagonizing the inhibitory effect of morphine on preovulatory surges of gonadotropins or PRL.     

Termination of unwanted pregnancy in dogs with the dopamine agonist, cabergoline, in combination with a synthetic analog of PGF2alpha, either cloprostenol or alphaprostol

Associations of a dopamine agonist, cabergoline, and a synthetic analog of PGF2alpha, either alphaprostol or cloprostenol, were used to induce pregnancy termination in 15 mature Beagle bitches. Alphaprostol (20 microg/kg/d) was injected subcutaneously (sc) in combination with cabergoline (1.65 microg/kg/d, sc) daily for 5 d from Day 32 after the LH peak in 5 animals. Cloprostenol 2.5 microg/kg/d in one group (n = 5) and 1 microg/kg/d in another group (n = 5) was also used in combination with the same dosage of cabergoline, following the same protocol, but starting from Day 25 after the LH peak. Treatment efficacy, defined by the number of pregnancy terminations, was 100% in all treated groups. Dose-related side effects due to PGF2alpha were observed (excessive salivation, prostration, vomiting, diarrhoea, scratching at the injection site), and were less severe with cloprostenol than with alphaprostol. In the group treated with the lowest dosage of cloprostenol, no adverse reactions were noticed. In all treated groups, interestrus intervals compared with previous cycles and in control animals were reduced after treatment.     

Luteolytic effects of prostaglandin F2alpha on day 8 to 19 corpora lutea in the bitch

Luteolysis was induced in 5 experimental Beagle (8 cycles) and 7 client-owned bitches treated with 150 to 200 microg/kg, sc of prostaglandin F2alpha administered twice daily for 4 d, starting on Days 8 to 19 after the onset of cytological diestrus. Five experimental Beagle bitches had been mated during the estrus preceding treatment, and copulation had been confirmed in 2/7 client-owned bitches presented for termination of unwanted pregnancy. Serum progesterone concentration (mean +/- SD) declined from 26.1 +/- 66 ng/ml before treatment to 0.3 +/- 0.4 ng/ml on the fourth day of treatment One of the 7 client-owned bitches maintained her pregnancy even though serum progesterone concentrations were less than 0.5 ng/ml on the third and fourth day of treatment. Mean (+/- SEM) inter-estrous intervals before and following prostaglandin-induced luteolysis were 207.3 +/- 12.4 (n = 11 cycles in 6 bitches) and 95.5 +/- 20.0 d (n = 6 cycles in the same 6 bitches; P < 0.0001), respectively These results suggest that effective prostaglandin-induced luteolysis can be achieved with administration of 180 microg/kg during the third week of diestrus in pregnant and nonpregnant bitches.     

Ovulation induction in anestrous bitches by pulsatile administration of gonadotropin-releasing hormone

Preliminary studies in anestrous Beagle bitches demonstrated that a single injection of gonadotropin-releasing hormone (150 micrograms) produced a rapid, physiological rise in serum estradiol lasting 1-3 days while progesterone remained below 1 ng/ml, whereas serial injections of FSH rapidly produced greater elevations in estradiol and a rapid rise in progesterone over 2 ng/ml. Consequently, attempts to induce fertile ovulation by means of pulsatile intravenous administration of GnRH (1 pulse/1.5 hours for 6-12 days; 0.04-0.43 micrograms/kg body weight/pulse) were conducted in eight anestrous bitches. Willingness to mate, serum progesterone levels and results of mating were monitored. In six of the eight bitches, vulval and vaginal signs of proestrus occurred by Day 2-4 after initiation of treatment (Day 0); but, two bitches showed negligible responses. In five of the six bitches in which proestrus was induced, behavioral (n = 4) and vaginal (n = 5) correlates of early estrus occurred by Day 5-7 of treatment and breedings occurred over a period of 4-12 days. Following onset of estrus, four of the five bitches had increases in serum progesterone levels between Days 14 and 18 after initiation of treatment (and 4-11 days after cessation of treatment); three of them became pregnant and whelped normal litters (ranging from 9 to 11 pups). The fifth bitch did not have elevated progesterone during the induced estrus, and upon return to estrus one month later was successfully bred and whelped a normal litter of 10 pups.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of exogenous progestin on the occurrence of proestrous or estrous signs, plasma concentrations of luteinizing hormone and estradiol in deslorelin (GnRH agonist) treated anestrous bitches

The objectives of this study were to confirm: (i) whether progestin treatment suppressed GnRH agonist-induced estrus in anestrous greyhound bitches; and (ii) the site of progestin action (i.e. pituitary, ovary). All bitches received a deslorelin implant on Day 0 and blood samples were taken from -1 h to +6 h. Five bitches were treated with megestrol acetate (2 mg/kg orally once daily) from -7 d to +6 d (Group 1) and 10 bitches were untreated controls (Group 2). Proestrous or estrous signs were observed in 4 of 5 bitches in Group 1, and 4 of 10 bitches in Group 2 (P = 0.28). The plasma LH responses (area under the curve from 0 to 6h after implantation) were higher (P = 0.008) in Group 2 than in Group 1. Plasma LH responses were similar (P = 0.59) in bitches showing signs of proestrus or estrus (responders) and in non-responders. The plasma estradiol responses (calculated as for LH response) were greater in Group 1 than in Group 2 (P = 0.048), and in responders than in non-responders (P = 0.02). In conclusion: (i) progestin treatment (a) did not suppress the incidence of bitches showing deslorelin-induced proestrus or estrus, and (b) was associated with a reduced pituitary responsiveness and an increased ovarian responsiveness to deslorelin treatment; (ii) the occurrence of proestrous or estrous signs reflected increased ovarian responsiveness to induced gonadotrophin secretion and not increased pituitary responsiveness to deslorelin.     

Evidence that physiological levels of circulating leptin exert a stimulatory effect on luteinizing hormone and prolactin surges in rats.

Increasing evidence suggests that leptin, an adipocyte-derived hormone, may positively regulate the reproductive axis, and serve as a critical metabolic signal linking nutrition and the reproductive function. However, along this line there remains an as-of-yet unresolved important issue whether physiological levels of circulating leptin exert a stimulatory effect on the reproductive axis. It is also unknown whether hyperleptinemia affects the reproductive function. In this study, we attempted to examine these unexplored issues, employing as an indicator the estradiol/progesterone-induced luteinizing hormone (LH) and prolactin (PRL) surges in ovariectomized female rats. Experiments were performed on normally fed, 3-day starved, 3-day starved + murine leptin (100 microg/kg/day), and normally fed + murine leptin (300 microg/kg/day) groups. Leptin was administered utilizing osmotic minipumps during 3 days immediately before experimentation. From 11:00 to 18:00 h, blood was collected every 30 min to measure LH and PRL. The 3-day starvation completely abolished both LH and PRL surges, but 3-day starved + leptin (100 microg/kg/day) group, whose plasma leptin levels (3.7 +/- 0.4 ng/ml) were similar to those in normally fed group (3.4 +/- 0.5 ng/ml), showed a significant recovery of the hormonal surges. On the other hand, the magnitudes of LH and PRL surges in normally fed + leptin (300 microg/kg/day) group, whose leptin levels were 10.8 +/- 1.5 ng/ml, were statistically the same as those in normally fed group. These results indicate for the first time that physiological concentrations of circulating leptin exert a stimulatory effect on the steroid-induced LH and PRL surges in the rat. It was also suggested that mild hyperleptinemia of 3 days' duration may not significantly affect the hormonal surges.     

Termination of pregnancy in dogs by oral administration of dexamethasone

Dexamethasone was administered orally for 7.5 or 10 d to each of 20 pregnant bitches beginning at an estimated 28 to 51 d of gestation, using 1 of 2 dose regimens. Five bitches were given dexamethasone 3 times a day for 10 d, with the highest dose of 0.2 mg/kg for 5 d and then at progressively decreasing doses of 0.16-0.02 mg/kg for 5 d. The 15 remaining bitches were given dexamethasone 2 times a day for 7.5 d, increasing from 0.1 to 0.2 mg/kg over the first 3 administrations, then remaining at 0.2 mg/kg on Days 2 to 5, and decreasing from 0.16 to 0.02 mg/kg over the last 5 administrations. The side effects, including mild polydipsia and polyuria, disappeared when treatment was discontinued. Depending on the stage of pregnancy, uterine contents were either resorbed or aborted, or both. Pregnancy was terminated within 2 to 16 d after the start of treatment in all treated bitches, at 2 to 5 d of treatment in 2 of 3 bitches treated at 40 to 51 d of pregnancy, and at 0 to 4 d after the end of treatment in most of the 17 bitches treated at 28 to 35 days of pregnancy. Oral administration of dexamethasone appears to be a potentially useful pharmacologic treatment for the termination of unwanted pregnancy in the bitch.     

Dose-dependent inhibition of the preovulatory surges of gonadotropins and prolactin by the antiestrogen CI-628: possible sites of action

The present series of experiments was conducted in an attempt to correlate previously reported dose-dependent and site-selective inhibitory effects of an antiestrogen, CI-628, on 17 beta-estradiol (E2)-receptor interactions in the anterior pituitary gland (AP) and hypothalamus with its effects on the preovulatory surges of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. The effects of CI-628 on the response of the AP to luteinizing hormone-releasing hormone (LHRH) and thyrotropin-releasing hormone (TRH) also were examined. In the first study, rats exhibiting 4-day estrous cycles were injected with various doses (0.02, 0.20, 2.0, and 20 mg/kg) of CI-628 or vehicle at 0900 h on diestrus-2 and proestrus. The preovulatory LH surge and both preovulatory and secondary FSH surges were marginally affected by 0.02 mg/kg CI-628, but were completely abolished by higher doses. In contrast, a dose of 0.20 mg/kg only delayed the prolactin surge; however, higher doses were effective in extinguishing cyclic prolactin release. In a second experiment, CI-628 in rats treated on diestrus-2 and proestrus exerted a dose-dependent suppression of the AP LH response to an initial injection of LHRH on proestrous afternoon in rats whose endogenous LH surges were blocked by phenobarbital. However, AP LH responses to a second LHRH injection to assess the self-priming capacity of LHRH were attenuated only in rats given 0.20, 2.0, and 20 mg/kg CI-628. Contrastingly, the AP prolactin response to TRH was suppressed only in rats given 0.20 mg/kg CI-628.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of ally-trenbolone as a progestational agent to maintain pregnancy in ovariectomized bitches

The administration of the synthetic progestogen, allytrenbolone, at a dose of 0.088 mg/kg/d per os successfully maintained pregnancy in 3 of 3 bitches ovariectomized at 34 to 42 d of gestation and in 1 of 3 ovariectomized on Day 8 or 9 of gestation. However, a dose of 0.044 mg/kg/d per os maintained pregnancy in only 2 of 6 bitches ovariectomized in mid-gestation. Two bitches that had ovariectomies performed on Day 9 of gestation and were supplemented with ally-trenbolone at a dose of 0.088 mg/kg/d per os did not establish a pregnancy that was detectable by mid-gestation. Although inhibited the first 2 d post partum in some bitches, lactation increased sufficiently to successfully maintain pups.