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

G. M. Davolli; B. A. Ball; A. Esteller-Vico; A. N.J. Claes; I. F. Canisso; C. E. Fedorka; E. M. Woodward; M. H.T. Troedsson; E. L. Squires

doi:10.1016/j.theriogenology.2016.07.021

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

G. M. Davolli, B. A. Ball, A. Esteller-Vico, A. N.J. Claes, I. F. Canisso, C. E. Fedorka, E. M. Woodward, M. H.T. Troedsson, E. L. Squires

Veterinary Science

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English
Pages (from-to)	2272-2280
Number of pages	9
Journal	Theriogenology
Volume	86
Issue number	9
DOIs	https://doi.org/10.1016/j.theriogenology.2016.07.021
State	Published - Dec 1 2016

Bibliographical note

Funding Information:
The authors are very grateful to Dr. Kirsten Scoggin, Jackie Barr, Michelle Gruss, Dr. Abdo Alghamdi, and Dr. Nathaniel Newton for helping with either data collection or analyses. They thank Dr. Jan Roser and Lillian Sibley, University of California-Davis, for performing gonadotropin assays. The horse care by the farm crew and management at Maine Chance Farm, Lexington, KY, was essential for this research. This study was funded by the Shapiro, Clay and Koller endowments of the Maxwell H. Gluck Equine Research Center , University of Kentucky. The acyline peptide was kindly provided by the National Institute of Child Health and Human Development (NICHD)/Contraceptive Discovery and Development Branch.

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

GnRH antagonist
Hypothalamic-pituitary-gonadal axis
Sexual behavior
Stallion
Testosterone suppression

ASJC Scopus subject areas

Small Animals
Food Animals
Animal Science and Zoology
Equine

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10.1016/j.theriogenology.2016.07.021

Cite this

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title = "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.",

keywords = "GnRH antagonist, Hypothalamic-pituitary-gonadal axis, Sexual behavior, Stallion, Testosterone suppression",

author = "Davolli, {G. M.} and Ball, {B. A.} and A. Esteller-Vico and Claes, {A. N.J.} and Canisso, {I. F.} and Fedorka, {C. E.} and Woodward, {E. M.} and Troedsson, {M. H.T.} and Squires, {E. L.}",

note = "Funding Information: The authors are very grateful to Dr. Kirsten Scoggin, Jackie Barr, Michelle Gruss, Dr. Abdo Alghamdi, and Dr. Nathaniel Newton for helping with either data collection or analyses. They thank Dr. Jan Roser and Lillian Sibley, University of California-Davis, for performing gonadotropin assays. The horse care by the farm crew and management at Maine Chance Farm, Lexington, KY, was essential for this research. This study was funded by the Shapiro, Clay and Koller endowments of the Maxwell H. Gluck Equine Research Center , University of Kentucky. The acyline peptide was kindly provided by the National Institute of Child Health and Human Development (NICHD)/Contraceptive Discovery and Development Branch. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

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AU - Ball, B. A.

AU - Esteller-Vico, A.

AU - Claes, A. N.J.

AU - Canisso, I. F.

AU - Fedorka, C. E.

AU - Woodward, E. M.

AU - Troedsson, M. H.T.

AU - Squires, E. L.

N1 - Funding Information: The authors are very grateful to Dr. Kirsten Scoggin, Jackie Barr, Michelle Gruss, Dr. Abdo Alghamdi, and Dr. Nathaniel Newton for helping with either data collection or analyses. They thank Dr. Jan Roser and Lillian Sibley, University of California-Davis, for performing gonadotropin assays. The horse care by the farm crew and management at Maine Chance Farm, Lexington, KY, was essential for this research. This study was funded by the Shapiro, Clay and Koller endowments of the Maxwell H. Gluck Equine Research Center , University of Kentucky. The acyline peptide was kindly provided by the National Institute of Child Health and Human Development (NICHD)/Contraceptive Discovery and Development Branch. Publisher Copyright: © 2016 Elsevier Inc.

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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