Contraceptive efficacy and dose-response effects of the gonadotrophin-releasing hormone (GnRH) agonist deslorelin in Tasmanian devils (Sarcophilus harrisii)

2019 ◽  
Vol 31 (9) ◽  
pp. 1473
Author(s):  
Holly R. Cope ◽  
Sarah Peck ◽  
Rebecca Hobbs ◽  
Tamara Keeley ◽  
Stephen Izzard ◽  
...  
Keyword(s):  
Dose Response ◽  
Optimal Dose ◽  
High Dose ◽  
Tasmanian Devil ◽  
Negative Effects ◽  
Releasing Hormone ◽  
Duration Of Effect ◽  
Gonadotrophin Releasing Hormone ◽  
Contraceptive Implants ◽  
Dose Response Effect

Contraception is increasingly used to manage breeding opportunities in conservation-dependent species. This study aimed to determine the efficacy, duration of effect, optimal dose and potential side effects of Suprelorin contraceptive implants in Tasmanian devils, for use in the conservation breeding program. In our pilot study, Suprelorin was found to effectively suppress oestrous cycles in female devils, yet caused a paradoxical increase in testosterone in males. Therefore, we focussed on females in further trials. Females received one (n=5), two (n=5) or no (n=5) Suprelorin implants, with quarterly gonadotrophin-releasing hormone (GnRH) challenges used to test pituitary responsiveness over two breeding seasons. Both Suprelorin doses suppressed pituitary responsiveness for at least one breeding season, with a reduced effect in the second. There was a dose-response effect on duration rather than magnitude of effect, with high-dose devils remaining suppressed for longer than low-dose animals. There were no apparent negative effects on general health, yet captivity and contraception together may cause weight gain. Suprelorin contraceptive implants are now routinely used in the Save the Tasmanian Devil Program insurance metapopulation to meet the aims of maintaining genetic and behavioural integrity by controlling individual reproductive contributions in group housing situations.

Varying the patterns and concentrations of gonadotrophin-releasing hormone stimulation does not alter the ratio of LH and FSH released from perifused sheep pituitary cells

1986 ◽  
Vol 109 (2) ◽  
pp. 155-161 ◽  
Author(s):  
J. E. A. McIntosh ◽  
R. P. McIntosh
Keyword(s):  
Dose Response ◽  
Dose Interval ◽  
Follicular Phase ◽  
Pituitary Cells ◽  
Ovulatory Cycle ◽  
Short Term ◽  
Releasing Hormone ◽  
Dissociated Cells ◽  
Gonadotrophin Releasing Hormone

ABSTRACT Our aim was to determine whether release of LH and FSH can be controlled differentially by the characteristics of applied signals of stimulatory gonadotrophin-releasing hormone (GnRH) alone, free of the effects of steroid feedback or other influences from the whole animal. The outputs of both gonadotrophins were significantly correlated (r≈0·90; P<0·0005) when samples of freshly dispersed sheep pituitary cells were perifused in columns for 7 h with medium containing a range of concentrations of GnRH in various patterns of pulses. Hormone released in response to the second, third and fourth pulses from every column was analysed in detail. Dose–response relationships for both LH and FSH were very similar when cells were stimulated with 5–8500 pmol GnRH/1 in 5-min pulses every hour. When GnRH was delivered in pulses at a maximally stimulating level, the outputs of both hormones increased similarly with increasing inter-pulse intervals. Efficiency of stimulation (release of gonadotrophin/unit stimulatory GnRH) decreased (was desensitized) with increasing pulse duration in the same way for both hormones. Thus, varying the dose, interval and duration of GnRH pulses did not alter the proportions of LH and FSH released in the short-term from freshly dissociated cells. However, the same cell preparations released more LH relative to FSH when treated with maximally stimulating levels of GnRH for 3 h in the presence of 10% serum from a sheep in the follicular phase of its ovulatory cycle compared with charcoal-treated serum. Because there was no gonadotrophin synthesis under the conditions used in vitro these results suggest that changes in the LH/FSH ratio seen in whole animals are more likely to result from differential clearance from the circulation, ovarian feedback at the pituitary, differential synthesis in intact tissue or another hormone influencing FSH secretion, rather than from differences in the mechanism of acute release controlled by GnRH. J. Endocr. (1986) 109, 155–161

Variable duration of reproductive suppression in male coyotes (Canis latrans) treated with a high dose of the gonadotrophin-releasing hormone agonist deslorelin

2017 ◽  
Vol 29 (7) ◽  
pp. 1271 ◽  
Author(s):  
Marjorie J. MacGregor ◽  
Cheryl S. Asa ◽  
Donal C. Skinner
Keyword(s):  
Canis Latrans ◽  
Animal Health ◽  
Management Strategies ◽  
High Dose ◽  
Sperm Production ◽  
Releasing Hormone ◽  
Reproductive Axis ◽  
Gonadotrophin Releasing Hormone ◽  
Breeding Seasons

Effective and humane management strategies for coyotes (Canis latrans) remain elusive. We hypothesised that exposure to a high dose of a gonadotrophin-releasing hormone (GnRH) agonist would cause prolonged suppression of the reproductive axis. Two groups of male coyotes were administered 47 mg deslorelin in the form of either five 9.4-mg controlled-release Suprelorin (Peptech Animal Health, Macquarie Park NSW, Australia) implants (n = 3) or 10 4.7-mg implants (n = 5). In the first group, deslorelin suppressed plasma LH, testosterone and testes volume in two of three coyotes for three breeding seasons. In the second group, two of five deslorelin-treated coyotes had no sperm production after 1 year and plasma LH, FSH, testosterone and testes volume were suppressed. Although plasma gonadotropins and testosterone were suppressed in three treated coyotes in group two, testes volume and sperm production were evident. Because the duration of suppression differed among individual coyotes, we further hypothesised that a variation in deslorelin release underlay the variability. To test this, we analysed in vivo plasma profiles of deslorelin concentrations. These profiles suggested that deslorelin concentrations >100 pg mL–1 are required to maintain suppression in male coyotes. For field implementation, the development of an implant capable of releasing deslorelin for the life of the coyote is necessary.

scholarly journals Dose Response Effect of High‐Dose Fluconazole for HIV‐Associated Cryptococcal Meningitis in Southwestern Uganda

2008 ◽  
Vol 47 (12) ◽  
pp. 1556-1561 ◽  
Author(s):  
Nicky Longley ◽  
Conrad Muzoora ◽  
Kabanda Taseera ◽  
James Mwesigye ◽  
Joselyne Rwebembera ◽  
...  
Keyword(s):  
Dose Response ◽  
Cryptococcal Meningitis ◽  
High Dose ◽  
Response Effect ◽  
Dose Response Effect ◽  
Southwestern Uganda

Re-evaluation of neurobehavioural toxicity of clothianidin using statistical methods for ordered alternatives assuming dose-response effect

2020 ◽  
pp. 074823372097927
Author(s):  
Toyohito Tanaka
Keyword(s):  
Statistical Methods ◽  
Dose Response ◽  
Dose Group ◽  
Exploratory Behaviour ◽  
High Dose Group ◽  
High Dose ◽  
Average Speed ◽  
Ordered Alternatives ◽  
Dose Response Effect ◽  
Williams Test

Neurobehavioural toxicity of clothianidin in previous studies was re-evaluated using statistical methods for ordered alternatives assuming a dose-response effect. In a maternal exposure study, clothianidin was added into the diet to provide levels of 0% (control), 0.002%, 0.006% and 0.018% during the gestation and lactation periods in mice. In exploratory behaviour of male offspring in the F1 generation, average speed increased significantly in a dose-related manner in the Jonckheere test. Total distance lengthened in the high-dose group and average speed increased in the high-dose group in the Shirley–Williams test. In a two-generation toxicity study, clothianidin was added in the diet to provide levels of 0% (control), 0.003%, 0.006% and 0.012% from 5 weeks of age of the F0 generation to 11 weeks of age of the F1 generation in mice. The exploratory behaviour of adult males in the F0 generation, the average time of movement, and the number of rearing and rearing time increased significantly in a dose-related manner in the Jonckheere test. The average speed increased in the middle- and high-dose groups, number of rearing increased in the high-dose group and rearing time lengthened in middle- and high-dose groups in the Shirley–Williams test. These results suggest that the use of the appropriate statistical methods adjusted to the objectives of the study and the characteristics of the data could provide more definite conclusions.

Effects of administration of testosterone and gonadotrophin-releasing hormone (GnRH) antagonist on basal and GnRH-stimulated gonadotrophin secretion in orchidectomized monkeys

1991 ◽  
Vol 129 (3) ◽  
pp. 363-370 ◽  
Author(s):  
S. Khurshid ◽  
G. F. Weinbauer ◽  
E. Nieschlag
Keyword(s):  
Gnrh Antagonist ◽  
Combined Treatment ◽  
High Dose ◽  
Similar Response ◽  
Primate Model ◽  
Gnrh Antagonists ◽  
Releasing Hormone ◽  
Gonadotrophin Secretion ◽  
Gonadotrophin Releasing Hormone ◽  
Range Study

ABSTRACT The aim of the present investigation was to investigate the effects of testosterone on basal and gonadotrophin-releasing hormone (GnRH)-stimulated gonadotrophin secretion in the presence and absence of a GnRH antagonist in a non-human primate model (Macaca fascicularis). Orchidectomized animals were used in order to avoid interference by testicular products other than testosterone involved in gonadotrophin feedback. Concomitant and delayed administration of testosterone at doses that provided serum levels either within the intact range (study 1) or markedly above that range (study 2) did not influence the suppression of basal gonadotrophin release induced by the GnRH antagonist during a 15-day period. To assess the possible effects of testosterone treatment at the pituitary level (study 3) GnRH stimulation tests (500 μg) were performed before and on days 8 and 15 of treatment with high-dose testosterone and GnRH antagonist alone or in combination. Testosterone alone abolished the gonadotrophin responses to exogenous GnRH observed under pretreatment conditions. With GnRH antagonist alone, an increased responsiveness (P <0·05) to GnRH was seen on day 8 and a similar response compared with pretreatment on day 15. Following combined treatment with GnRH antagonist and testosterone, GnRH-induced gonadotrophin secretion was consistently lower compared with that after GnRH antagonist alone (P <0·05), but was increased compared with that after testosterone alone (P<0·05). Thus, in the presence of a GnRH antagonist the feedback action of testosterone on LH and FSH was diminished. The present work in GnRH antagonist-treated orchidectomized monkeys demonstrates that (I) unlike in rats, testosterone fails to stimulate FSH secretion selectively, (II) the negative feedback action of testosterone on GnRH-stimulated LH and FSH secretion is altered in the presence of a GnRH antagonist and (III) GnRH antagonists induce a transient period of increased responsiveness of gonadotrophic hormone release to exogenous GnRH. The observation that a GnRH antagonist reduced the feedback effects of testosterone suggests that testosterone action on pituitary gonadotrophin release, at least in part, is mediated via hypothalamic GnRH. Journal of Endocrinology (1991) 129, 363–370

Dose-response in the treatment of hypercalcemia of malignancy by a single infusion of the bisphosphonate AHPrBP.

1988 ◽  
Vol 6 (5) ◽  
pp. 762-768 ◽  
Author(s):  
D Thiébaud ◽  
P Jaeger ◽  
A F Jacquet ◽  
P Burckhardt
Keyword(s):  
Dose Response ◽  
Low Dose ◽  
Optimal Dose ◽  
Urinary Calcium ◽  
Plasma Calcium ◽  
High Dose ◽  
Initial Plasma ◽  
Plasma Calcium Concentration ◽  
Dose Dependent Decrease

Fifty-two patients with malignant hypercalcemia were treated with a single dose of 3-amino-1-hydroxypropylidene-1,1- bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose-response in humans, patients were divided into four groups receiving 30 mg, 45 mg, 60 mg, or 90 mg, respectively, as a 24-hour infusion. Initial plasma calcium was similar in all groups, except in the group receiving 90 mg, of which some patients had higher initial values. All patients responded to AHPrBP with a rapid decrease of plasma calcium concentration from 3.47 +/- 0.10 mmol/L at day 0 to 2.43 +/- 0.06 at day 6 (P less than .001). Plasma calcium became normal within four to six days in 43 patients. Eight of the nine patients whose calcium did not become normal were in the low-dose (30 and 45 mg of AHPrBP) groups. Slight and asymptomatic hypocalcemia occurred in only tow of the 26 patients in the low-dose groups, but in six of the 26 patients in the high-dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 1 month in five of ten patients in the group receiving 30 mg, in three of ten patients in the group receiving 45 mg, and in one of 20 patients in the groups receiving 60 and 90 mg, whereas mortality was almost identical in all four groups. In all groups, plasma phosphate, plasma creatinine, urinary calcium, and hydroxyproline excretion decreased significantly. In conclusion, when administered as a single-day infusion in the treatment of tumor hypercalcemia, AHPrBP leads to a dose-dependent decrease in plasma calcium. To prevent transient hypocalcemia and early relapse, the optimal dose should be adapted to the degree of severity of hypercalcemia.

Sign in / Sign up

Export Citation Format

Share Document