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.
authors: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: G M
authors: GM
authors: Davolli
authors: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA. Electronic address: b.a.ball@uky.edu.
authors: B A
authors: BA
authors: Ball
authors: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: A
authors: A
authors: Esteller-Vico
authors: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: A N J
authors: AN
authors: Claes
authors: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: I F
authors: IF
authors: Canisso
authors: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: C E
authors: CE
authors: Fedorka
authors: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: E M
authors: EM
authors: Woodward
authors: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: M H T
authors: MH
authors: Troedsson
authors: Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, Kentucky, USA.
authors: E L
authors: EL
authors: Squires
mesh_terms: D000818:Animals; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006736:Horses / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013737:Testis / Q000502:physiology*; D013739:Testosterone / Q000097:blood
chemical_list: C504459:FILIP1L protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides; D004970:Estrone; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C017296:estrone sulfate; C109238:acyline
keywords: GnRH antagonist; Hypothalamic-pituitary-gonadal axis; Sexual behavior; Stallion; Testosterone suppression