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

Author

Davolli, G M, Ball, B A, Esteller-Vico, A, Claes, A N J, Canisso, I F, Fedorka, C E, Woodward, E M, Troedsson, M H T, Squires, E L, LS Voortplanting Inwendige Ziekten, and dES/dFAH FR

Subjects
Sexual behavior, Male, Hypothalamo-Hypophyseal System, endocrine system, medicine.medical_specialty, Estrone, Hypothalamic–pituitary–gonadal axis, Gonadotropin-releasing hormone, Gonadotropin-Releasing Hormone, Andrology, Sexual Behavior, Animal, 03 medical and health sciences, chemistry.chemical_compound, Follicle-stimulating hormone, Testosterone suppression, 0302 clinical medicine, Food Animals, Estrone sulfate, Internal medicine, Testis, GnRH antagonist, medicine, Animals, Testosterone, Horses, Small Animals, Stallion, 030219 obstetrics & reproductive medicine, Equine, business.industry, Intracellular Signaling Peptides and Proteins, 0402 animal and dairy science, 04 agricultural and veterinary sciences, Luteinizing Hormone, 040201 dairy & animal science, Sperm, Endocrinology, chemistry, Animal Science and Zoology, Follicle Stimulating Hormone, business, Luteinizing hormone, Hypothalamic-pituitary-gonadal axis, Oligopeptides
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.

Published
2016
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4. Reversible downregulation of the hypothalamic-pituitary-gonadal axis in stallions with a novel GnRH antagonist

Author

LS Voortplanting Inwendige Ziekten, dES/dFAH FR, Davolli, G M, Ball, B A, Esteller-Vico, A, Claes, A N J, Canisso, I F, Fedorka, C E, Woodward, E M, Troedsson, M H T, Squires, E L, LS Voortplanting Inwendige Ziekten, dES/dFAH FR, Davolli, G M, Ball, B A, Esteller-Vico, A, Claes, A N J, Canisso, I F, Fedorka, C E, Woodward, E M, Troedsson, M H T, and Squires, E L

Published
2016

6. Inhibin-A and Inhibin-B in stallions: Seasonal changes and changes after down-regulation of the hypothalamic-pituitary-gonadal axis.

Author

Ball BA, Davolli GM, Esteller-Vico A, Fleming BO, Wynn MAA, and Conley AJ

Subjects
Animals, Down-Regulation, Estrone analogs & derivatives, Estrone blood, Horses blood, Hypothalamo-Hypophyseal System physiology, Male, Oligopeptides administration & dosage, Oligopeptides pharmacology, Random Allocation, Seasons, Testis physiology, Testosterone blood, Horses physiology, Hypothalamo-Hypophyseal System drug effects, Inhibins metabolism, Testis drug effects
Abstract

The biological function of inhibin is mediated by two heterodimers, inhibin-A and inhibin-B. The relative importance of inhibin-A and -B in male reproductive function varies considerably across species with inhibin-B predominating in many species, whereas inhibin-A appears relatively more important in rams. Research reported to date in stallions has examined total or immunoreactive (ir) inhibin which does not distinguish the two heterodimers. Therefore, the objective of this study was to characterize changes in inhibin-A and inhibin-B concentrations in stallions: 1) across season for a period of one year, and 2) after downregulation of the hypothalamic-pituitary-gonadal (HPG) axis. In Study one, serum samples were obtained monthly from five stallions for a period of one year. Serum concentrations of inhibin-A, inhibin-B, testosterone and estrone sulfate were determined by ELISA. In Study two, stallions were treated with the GnRH antagonist, acyline (n = 4; 330 mg/kg acyline IM) or vehicle control (n = 4; vehicle alone) every five days for 50 days. Plasma concentrations of inhibin-A and -B were determined by ELISA at Days 0, 6, 12, 22, 37, 59, 80, 87 and 104 after initiation of acyline treatment. Testis volume was determined by ultrasonography at weekly intervals. In Study 1, both inhibin-A and inhibin-B showed seasonal changes in concentration with highest concentrations in increasing day length and lowest concentrations in short day lengths. Inhibin-B (overall mean 107.8 ± 4.1 pg/mL) was present at 4.7-fold higher concentrations in serum than inhibin-A (overall mean 23.0 ± 0.7 pg/mL). In Study 2, plasma concentrations of inhibin-B but not inhibin-A were significantly downregulated by administration of the GnRH antagonist, acyline. When the HPG axis was downregulated by acyline, testis volume was strongly correlated with inhibin-B (r = 0.73; P < 0.05) but not inhibin-A (r = 0.22; P = 0.20). In summary, inhibin-B appears to be the predominant form of inhibin in the stallion which undergoes seasonal regulation along with other reproductive parameters and is co-regulated with other endocrine parameters of the HPG axis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Published
2019
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