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Theriogenology2016; 86(9); 2272-2280; doi: 10.1016/j.theriogenology.2016.07.021

Reversible downregulation of the hypothalamic-pituitary-gonadal axis in stallions with a novel GnRH antagonist.

Abstract: The GnRH antagonist, acyline, has not yet been investigated in the stallion. Our study aimed to: (1) evaluate the downregulation of the stallion hypothalamic-pituitary-gonadal axis by acyline through assessment of seminal parameters, testicular volume, and sexual behavior; (2) assess hormonal response of acyline-treated stallions to GnRH stimulation; and (3) verify reversibility after treatment. Stallions were assessed pretreatment and subsequently treated (every five days) for 50 days: acyline (n = 4; 330 μg/kg acyline) or control (n = 4, vehicle). The stallions were then monitored for 62 days after the last day of treatment. Treatment-induced declines (P < 0.05) in FSH, LH, testosterone, and estrone sulfate. Gonadotropins and testosterone returned to control values within 9 days, and estrone sulfate by 14 days, after discontinuation of treatment. Acyline-treated stallions failed to respond with a rise in FSH, LH, and testosterone after exogenous GnRH stimulation (gonadorelin) at Day 46 of treatment compared to pretreatment stimulation and control stallions. Decreases (P < 0.05) were observed in total sperm numbers and motility (week 2) in acyline-treated stallions, as well as total seminal plasma protein (week 2) and testicular volume (week 5). Over the course of the study, the time to erection, time to ejaculation, and number of mounts increased (P < 0.0001) across both groups of stallions; however, there was no effect of treatment or treatment by time interactions on these parameters. Testicular volume, and most seminal parameters regained normal levels within 62 days after treatment ended; on follow-up, sperm output of acyline-treated stallions was regained within 7 months after the end of experiment. In conclusion, acyline reversibly suppresses the stallion hypothalamic-pituitary-gonadal axis.
Publication Date: 2016-07-26 PubMed ID: 27570103DOI: 10.1016/j.theriogenology.2016.07.021Google Scholar: Lookup
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  • Journal Article

Summary

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The research article explores the impact of the GnRH antagonist, acyline, on stallions, focusing on its effects on the reproductive system. The study finds that acyline successfully suppresses the function of the hypothalamic-pituitary-gonadal axis, affecting hormone levels, seminal parameters, and testicular volume, but these effects are reversible after discontinuation of treatment.

Study Objectives and Methodology

  • The research had three main objectives. First, to understand the impact of acyline on the reproductive system of stallions by assessing seminal parameters, testicular volume, and sexual behavior. Second, to examine the hormonal response of acyline-treated stallions to GnRH stimulation. Finally, to confirm whether the effects of acyline treatment are reversible.
  • A total of eight stallions were included in the experiment, with four receiving acyline treatment and four serving as control subjects. The acyline-treated stallions were given doses of 330 μg/kg of the drug every five days for a period of 50 days. These stallions were then monitored for a period of 62 days following the last day of treatment.

Key Findings

  • The study found that acyline treatment caused a decrease in the levels of several hormones such as FSH, LH, testosterone, and estrone sulfate. However, these levels returned to normal within 9-14 days after the discontinuation of treatment.
  • When the acyline-treated stallions were subjected to exogenous GnRH stimulation (gonadorelin) at Day 46 of treatment, they failed to show any rise in FSH, LH, and testosterone levels. This was in contrast to the response seen before treatment and in control stallions.
  • Acyline treatment also negatively affected total sperm numbers and motility, seminal plasma protein levels, and testicular volume. These effects were observed within the first 2-5 weeks of acyline treatment.
  • The study also noticed changes in sexual behavior, such as increased time to erection, time to ejaculation, and number of mounts across all stallions during the course of the study. However, acyline treatment had no distinct effect on these parameters.
  • Most importantly, the study found these changes to be reversible. Testicular volume and seminal parameters returned to normal levels within 62 days after ending treatment. The sperm output of acyline-treated stallions was regained within 7 months after the end of the experiment.

Conclusion

  • The results of the study indicate that while acyline suppresses the reproductive function of stallions as evidenced by the changes in hormonal levels, seminal parameters, and testicular volume, this downregulation is reversible. The findings of the study suggest that GnRH antagonists such as acyline could be used to manage and control the reproduction of stallions.

Cite This Article

APA
Davolli GM, Ball BA, Esteller-Vico A, Claes AN, Canisso IF, Fedorka CE, Woodward EM, Troedsson MH, Squires EL. (2016). Reversible downregulation of the hypothalamic-pituitary-gonadal axis in stallions with a novel GnRH antagonist. Theriogenology, 86(9), 2272-2280. https://doi.org/10.1016/j.theriogenology.2016.07.021

Publication

ISSN: 1879-3231
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 86
Issue: 9
Pages: 2272-2280
PII: S0093-691X(16)30330-2

Researcher Affiliations

Davolli, G M
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Ball, B A
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA. Electronic address: b.a.ball@uky.edu.
Esteller-Vico, A
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Claes, A N J
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Canisso, I F
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Fedorka, C E
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Woodward, E M
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Troedsson, M H T
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
Squires, E L
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.

MeSH Terms

  • Animals
  • Estrone / analogs & derivatives
  • Estrone / blood
  • Follicle Stimulating Hormone / blood
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Horses / physiology
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / physiology
  • Intracellular Signaling Peptides and Proteins
  • Luteinizing Hormone / blood
  • Male
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacology
  • Sexual Behavior, Animal / drug effects
  • Testis / physiology
  • Testosterone / blood

Citations

This article has been cited 1 times.
  1. Kawate N, Kanuki R, Hannan MA, Weerakoon WWPN. Inhibitory effects of long-term repeated treatments of a sustainable GnRH antagonist, degarelix acetate, on caprine testicular functions. J Reprod Dev 2020 Dec 22;66(6):587-592.
    doi: 10.1262/jrd.2020-035pubmed: 32830151google scholar: lookup