Effectiveness of an antagonist to gonadotrophin releasing hormone on the FSH and LH response to GnRH in perifused equine pituitary cells, and in seasonally acyclic mares.
Abstract: We wish to use a gonadotrophin-releasing hormone (GnRH) antagonist in the mare as a tool for investigating the control of the oestrous cycle. The aim of this study was to test the effectiveness of the antagonist cetrorelix by testing both in vitro, using perifused equine anterior pituitary cells, and in vivo in seasonally acyclic mares. Pituitary cells were prepared and after 3-4 days incubation, loaded onto columns and given four pulses of GnRH (at 0, 30, 60 and 90 min; dose-response study). After the second GnRH pulse, infusion of cetrorelix began (0, 100, 1000 and 2000 pmol/l) and continued until the end of the experiment. To mimic luteal phase conditions, cells were pre-incubated and perifused with progesterone (25 nmol/l) and GnRH pulses given at 0, 90, 180 and 270 min. Cetrorelix (0 or 1000 pmol/l) began after the second GnRH pulse. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were measured in 5 min fractions. Both FSH and LH response areas (above baseline) after GnRH were inhibited by 1000 pmol/l cetrorelix (P < 0.01, P < 0.01, respectively) but not by 100 pmol/l cetrorelix. Similarly, in the presence of progesterone, cetrorelix inhibited the FSH (P < 0.001) and LH (P = 0.0002) response area. Seasonally acyclic mares, pre-treated for 3 days with progesterone (150 mg i.m. per day) were given cetrorelix as (i) a loading dose of 1 microg/kg then infusion at 2.2 ng/(kg min) for 90 min, (ii) a s.c. injection at 20 microg/kg, (iii) infusion at 2.2 ng/(kg min) for 48 h, and (iv) no cetrorelix (control mares). At 90 min, 6, 24 and 48 h after cetrorelix was first administered, mares were given a bolus injection of GnRH (22.2 ng/kg i.v.) and the FSH and LH responses measured. All doses of cetrorelix inhibited the FSH response at 90 min. The response was no longer suppressed at 6 h in the 90 min infusion group, showing a rapid recovery from inhibition. At 24 h, the FSH responses in the injected and 48 h infusion group were suppressed. The LH concentrations were low and showed no significant changes. This study has defined the time course and dose of cetrorelix with respect to its effect on FSH in the horse. It is concluded that cetrorelix could be used to elucidate the role of FSH in follicular development in cyclic mares.
Copyright 2002 Elsevier Science B.V.
Publication Date: 2002-09-11 PubMed ID: 12220817DOI: 10.1016/s0378-4320(02)00130-6Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers examined the effectiveness of a gonadotrophin-releasing hormone (GnRH) antagonist called cetrorelix in understanding the control of oestrous cycles in mares. The study, conducted both in vitro and in vivo, found that cetrorelix can inhibit the follicle-stimulating hormone (FSH) and luteinizing hormone (LH) responses, suggesting its potential use in investigating FSH’s role in female reproductive cycles.
Research Design
- The study was designed to test the effectiveness of the GnRH antagonist cetrorelix, both in vitro (using perifused equine pituitary cells) and in vivo (in seasonally acyclic mares).
- Pituitary cells were prepared and incubated for 3-4 days and then processed by series of GnRH pulses. During the second GnRH pulse, cetrorelix infusion began and continued until the end of the experiment.
- Under the lab condition, the pituitary cells were perifused with progesterone to recreate luteal phase conditions. Here, after the progesterone treatment, GnRH pulses were administered and cetrorelix infusion started after the second GnRH pulse.
- In addition to the lab experiment, the researchers also investigated the effect of cetrorelix in seasonally acyclic mares. They were pre-treated with progesterone for three days and then given cetrorelix in various forms and doses.
Key Findings
- Both the FSH and LH responses after GnRH were inhibited by a higher concentration of cetrorelix (1000 pmol/l) but not by a lower concentration (100 pmol/l).
- Progesterone exposure also resulted in FSH and LH response inhibition by cetrorelix, with FSH inhibition being extremely significant.
- In seasonally acyclic mares, all investigated doses of cetrorelix suppressed the FSH response after 90 minutes. However, the response recovered after 6 hours in the group receiving a 90-minute infusion of cetrorelix.
- At 24 hours post cetrorelix administration, FSH responses in the injected and 48-hour infusion groups were still suppressed. Meanwhile, there were no significant changes observed in LH concentrations.
Conclusion
- The study concludes that cetrorelix has considerable effects on FSH secretion in mares, both in a laboratory setting and in living horses. The response to the antagonist was time-dependent and dose-sensitive.
- This work aids in understanding the role of FSH in follicular development in cyclic mares and suggests that cetrorelix could serve as a useful tool in related research fields.
Cite This Article
APA
Evans MJ, Kitson NE, Alexander SL, Irvine CH, Turner JE, Perkins NR, Livesey JH.
(2002).
Effectiveness of an antagonist to gonadotrophin releasing hormone on the FSH and LH response to GnRH in perifused equine pituitary cells, and in seasonally acyclic mares.
Anim Reprod Sci, 73(1-2), 37-51.
https://doi.org/10.1016/s0378-4320(02)00130-6 Publication
Researcher Affiliations
- Department of Endocrinology, Christchurch Hospital, Christchurch, New Zealand. margaret.evans@chmeds.ac.nz
MeSH Terms
- Animals
- Cells, Cultured
- Dose-Response Relationship, Drug
- Estrus
- Female
- Follicle Stimulating Hormone / antagonists & inhibitors
- Gonadotropin-Releasing Hormone / analogs & derivatives
- Gonadotropin-Releasing Hormone / blood
- Gonadotropin-Releasing Hormone / drug effects
- Gonadotropin-Releasing Hormone / pharmacology
- Hormone Antagonists / pharmacology
- Horses / blood
- Horses / physiology
- Luteinizing Hormone / blood
- Luteinizing Hormone / drug effects
- Radioimmunoassay / veterinary
- Random Allocation
- Time Factors
Citations
This article has been cited 2 times.- Tsukada T, Kojima AY, Sato K, Moriyoshi M, Koyago M, Sawamukai Y. Intrafollicular Concentrations of Steroid Hormones and PGF2α in Relation to Follicular Development in the Mares during the Breeding Season. J Equine Sci 2008;19(2):31-4.
- Silva ME, Smulders JP, Guerra M, Valderrama XP, Letelier C, Adams GP, Ratto MH. Cetrorelix suppresses the preovulatory LH surge and ovulation induced by ovulation-inducing factor (OIF) present in llama seminal plasma. Reprod Biol Endocrinol 2011 May 30;9:74.
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