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Article ; Online: Characterization and co-localization of thyroid stimulating hormone and melatonin receptors in the pars tuberalis of mares during the breeding and non-breeding seasons

Bailey, Victoria N / Gilbert, Bryce M / Oberhaus, Erin L

Journal of Equine Veterinary Science. 2023 June, v. 125 p.104690-

2023

Abstract: Control of seasonal reproduction in horses has yet to be fully elucidated; however, duration of melatonin secretion is a seasonal regulator of the hypothalamic-pituitary-gonadal (HPG) axis. The hypophyseal pars tuberalis (PT) appears to play a key role ... ...

Abstract	Control of seasonal reproduction in horses has yet to be fully elucidated; however, duration of melatonin secretion is a seasonal regulator of the hypothalamic-pituitary-gonadal (HPG) axis. The hypophyseal pars tuberalis (PT) appears to play a key role in the transduction of melatonin signal through melatonin responsive, PT-specific cells that produce thyroid stimulating hormone (TSH). The objectives of these experiments were to characterize and colocalize TSH-producing cells and melatonin receptors (MT1r) in the PT during breeding and non-breeding seasons. Pituitaries from nine light-horse type mares, aged 6 to 26 years, were obtained following euthanasia during the breeding and non-breeding seasons. Mares were determined to be either cycling (n = 5) or seasonally anovulatory (n = 4) based on season, gross inspection of ovarian structures, and plasma progesterone concentrations. Immediately following euthanasia, the carotid artery was perfused with sodium nitrite and 4% paraformaldehyde before decapitation and dissection of PT from the hypophysis. Immunofluorescent detection of TSH was carried out on fixed-frozen PT sections and number of immunopositive cells per 1 mm2 were counted and averaged for three replications per horse to compare TSH distribution between breeding and non-breeding season using Mann Whitney U test. TSH-immunoreactive cells were present in PT and were greater (P < 0.05) in PT during the breeding season comparedto non-breeding season; few to no immunoreactive cells were seen in PT from non-breeding season. In situ hybridization (ISH) was carried out using RNAscope HD Red Detection Kit and a custom MT1r probe (Ec-MTNR1A) to confirm MT1r localization and compare MT1r distribution between breeding and non-breeding seasons. Mean percentage of MT1r immunopositive cells, determined as a percentage of total number of cells, and expression of MT1r mRNA per cell, determined as mean number of dots (representing mRNA) per cell, were analyzed using Mann Whitney U test. Melatonin receptor mRNA was densely expressed in glandular cells of the PT and no differences were found in either percent immunopositive cells or mean number of mRNA dots per cell between breeding and non-breeding seasons. To determine if MT1r colocalize with TSH-producing cells, ISH was carried out alongside immunofluorescent detection of TSH as previously described. In cycling mares, MT1r mRNA colocalized with TSH-producing cells in the PT; however, not all TSH-producing cells colocalized with MT1r and vice versa. Lack of TSH-producing cells accounted for absence of colocalization in seasonally anovulatory mares. The PT is considered a major target for melatonin, and colocalization with TSH supports a role for TSH as a modulator of seasonal reproduction in the mare. This is further evidenced by increased TSH immunosignal during the breeding season.
Keywords	anovulation ; carotid arteries ; decapitation ; dissection ; hybridization ; mares ; melatonin ; pituitary gland ; progesterone ; secretion ; sodium nitrite ; veterinary medicine
Language	English
Dates of publication	2023-06
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	2102631-2
ISSN	1542-7412 ; 0737-0806
ISSN (online)	1542-7412
ISSN	0737-0806
DOI	10.1016/j.jevs.2023.104690
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Molecular mechanisms underlying equine endometrial cup regression: a transcriptomic analysis

Gomes, Viviane CL / Crissman, Kassandra R. / Oberhaus, Erin L. / Sones, Jenny L.

Journal of Equine Veterinary Science. 2023 June, v. 125 p.104768-

2023

Abstract: The gonadotropin-secreting equine endometrial cups (EC) have a major role in pregnancy maintenance, but an intriguingly short lifespan. First seen in the maternal endometrium at days (d) 38-40 post-ovulation, the EC undergo degeneration via poorly ... ...

Abstract	The gonadotropin-secreting equine endometrial cups (EC) have a major role in pregnancy maintenance, but an intriguingly short lifespan. First seen in the maternal endometrium at days (d) 38-40 post-ovulation, the EC undergo degeneration via poorly understood mechanisms starting around d 60-70, with complete dehiscence at approximately 120-150 d of gestation. Pregnancy losses during the EC physiological lifespan and EC pathological persistence after abortion or uncomplicated parturition usually lead to irregular estrous cyclicity and subfertility, with only anecdotal and inconsistent therapeutic options currently available. A holistic understanding of the cellular signaling leading to EC regression may provide insight for development of effective therapies for retained or persistent EC. We therefore hypothesized that comparing the transcriptome of EC during development and regression could elucidate key regulators and molecular pathways leading to EC trophoblast cell demise. Samples of EC were dissected from the adjacent endometrium of pregnant pony mares during early development (DEC, 42-47 d post-ovulation, n = 5), and regression (REC, 96 – 120 d, n = 5). Next generation RNA sequencing was performed with Illumina NovaSeq6000 and reads mapped to EquCab3.0 (STAR-2.5.2b). Differentially expressed genes (DEGs) were identified with Cuffdiff-2.2.1 (FDR < 0.05). A total of 2,504 DEG were identified, being 1,648 upregulated and 856 downregulated in REC when compared to DEC. Pathway Analysis of DEGs was also performed (IPA, Qiagen). Interestingly, the main pathways affected in REC included oxidative phosphorylation (P = 1.08e-38);mitochondrial dysfunction (P = 2e-25); estrogen receptor signaling (P = 2.2e-10); Sirtuin signaling pathway (P = 9.64e-16), which has central regulatory roles in cell senescence and apoptosis; and Granzyme A Signaling (3.29e-15), associated with Cytotoxic T Lymphocyte and Natural Killer-mediated apoptosis via caspase-independent pathways. Upstream regulator analysis highlighted the roles of mitochondrial protein ubiquinol-cytochrome c reductase complex-3; rapamycin-insensitive companion of mTOR, an essential molecule in cellular homeostasis; Torin-1, a potent mTOR inhibitor; dead box protein 5, which may act as a co-activator of estrogen receptor signaling; and transducing-like enhancer protein-3, a member of a family of proteins that regulate cell fate through the Notch signaling pathway. Importantly, the main upstream regulators and downstream molecules are also involved in cancer cell biology (P = 1.32e-07 – 1.71e-122), including the downstream effectors of neoplastic and epithelial cell death secreted phosphoprotein 1 (Spp1), and secreted protein acidic and cysteine rich (Sparc). Along with aromatase, Spp1 and Sparc were upregulated in REC in comparison to DEC. In summary, we have highlighted key molecular pathways and regulators of EC regression, which merit further molecular and functional investigations. Since multiple identified molecules have also been targeted in human oncological treatments, further investigation of their effectiveness in hastening EC demise is warranted.
Keywords	RNA ; T-lymphocytes ; apoptosis ; aromatase ; cell senescence ; cysteine ; cytotoxicity ; dehiscence ; early development ; endometrium ; epithelial cells ; estrogen receptors ; gene expression regulation ; homeostasis ; horses ; humans ; longevity ; mitochondrial proteins ; neoplasm cells ; oxidative phosphorylation ; parturition ; periodicity ; phosphoproteins ; pregnancy ; protein secretion ; sirtuins ; therapeutics ; transcriptome ; transcriptomics ; trophoblast ; veterinary medicine
Language	English
Dates of publication	2023-06
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	2102631-2
ISSN	1542-7412 ; 0737-0806
ISSN (online)	1542-7412
ISSN	0737-0806
DOI	10.1016/j.jevs.2023.104768
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Article: Sucrose Acetate Isobutyrate (SAIB) as a Delivery Vehicle for Estradiol and Sulpiride: Evaluation of Endocrine Responses in Geldings and Ovarian Response in Seasonally Anovulatory Mares.

Oberhaus, Erin L / Wilson, Kaitlyn M / Camp, Caroline M / Sones, Jenny L

Journal of equine veterinary science

2022 Volume 112, Page(s) 103896

Abstract: Sulpiride in vegetable shortening (VS) stimulates prolactin in horses for up to 10 days. Although effective, a pharmaceutical grade vehicle is needed for clinical application of sulpiride in horses. Sucrose acetate isobutyrate (SAIB), a hydrophobic ... ...

Abstract	Sulpiride in vegetable shortening (VS) stimulates prolactin in horses for up to 10 days. Although effective, a pharmaceutical grade vehicle is needed for clinical application of sulpiride in horses. Sucrose acetate isobutyrate (SAIB), a hydrophobic polymer, may be an alternative to VS. Four in vivo experiments assessed the efficacy of SAIB for delivery of sulpiride, estradiol cypionate (ECP), and estradiol benzoate (EB). The first three studies utilized geldings to compare prolactin and luteinizing hormone (LH) concentrations between sulpiride delivered in VS and SAIB, and ECP or EB delivered in SAIB. Sulpiride stimulated (P < .01) prolactin similarly between vehicles. Geldings pretreated with EB had higher (P < .05) prolactin responses to sulpiride compared to ECP-treated geldings on days 5, 6 and 9. Both estradiol-sulpiride treatments stimulated LH with no differences between ECP and EB. Experiment 3 compared a simultaneous injection of EB-sulpiride to a non-simultaneous injection (one day apart) of EB-sulpiride. Prolactin was stimulated (P < .05) in both treatment groups, but the response lasted 2 days longer in geldings treated a day apart. Plasma LH increased (P < .01) in both groups equally for 10 days. Experiment 4 applied simultaneous and non-simultaneous EB-sulpiride treatments to seasonally anovulatory mares to induce ovarian activity. Prolactin and LH were stimulated similarly between treatments; however, non-simultaneously treated mares tended (P = .07) to have an ovarian response earlier. In conclusion, SAIB was a suitable vehicle for administration of estradiol and sulpiride and could be an alternative to VS for sustained-release drug delivery.
MeSH term(s)	Animals ; Anovulation/veterinary ; Estradiol ; Female ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone ; Horse Diseases ; Horses ; Luteinizing Hormone ; Male ; Prolactin ; Sucrose/analogs & derivatives ; Sulpiride/pharmacology
Chemical Substances	Gonadotropin-Releasing Hormone (33515-09-2) ; Estradiol (4TI98Z838E) ; Sucrose (57-50-1) ; Sulpiride (7MNE9M8287) ; Prolactin (9002-62-4) ; Luteinizing Hormone (9002-67-9) ; Follicle Stimulating Hormone (9002-68-0) ; sucrose acetate isobutyrate (H5KI1C3YTV)
Language	English
Publishing date	2022-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2102631-2
ISSN	1542-7412 ; 0737-0806
ISSN (online)	1542-7412
ISSN	0737-0806
DOI	10.1016/j.jevs.2022.103896
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Article ; Online: Immunohistochemical localization of kisspeptin and kisspeptin receptor in the equine ovary: Effect of follicle size and reproductive state

Gilbert, Bryce M / Bailey, Victoria N / Gomes, Viviane CL / Sones, Jenny L / Oberhaus, Erin L

Journal of Equine Veterinary Science. 2023 June, v. 125 p.104713-

2023

Abstract: Kisspeptin is considered a regulator of reproduction by stimulating GnRH; however, extra-hypothalamic actions of kisspeptin have been described. The aim of this study was to localize kisspeptin-10 (Kp10) and kisspeptin receptor (Kiss1r) in the ovary and ... ...

Abstract	Kisspeptin is considered a regulator of reproduction by stimulating GnRH; however, extra-hypothalamic actions of kisspeptin have been described. The aim of this study was to localize kisspeptin-10 (Kp10) and kisspeptin receptor (Kiss1r) in the ovary and compare staining intensity between follicles in follicular-phase (FP) and luteal-phase (LP) ovaries, as well as between seasonally anovulatory (SA) ovaries and ovaries from mares induced to cycle in winter with estradiol cypionate (ECP) and sulpiride. Eight ovaries were collected from light-horse mares during the breeding and non-breeding seasons and characterized as FP (n = 3), LP (n = 2), or SA (n = 3). Additionally, 3 ovaries were collected from SA mares treated with ECP and sulpiride upon detection of the first 30-mm follicle after treatment. Immunohistochemistry was carried out on whole-ovarian, paraffin-embedded sections using anti-Kp10 and anti-Kiss1r antibodies validated on equine hypothalamus. Staining intensity was evaluated in primordial, preantral, and antral follicles using a scale of 0-3. Given a normal distribution, two-way ANOVA was used to compare staining between follicle sizes and reproductive states. Staining for Kp10 and Kiss1r was detected in all follicle sizes throughout all reproductive states, as well as in oocytes and corpora lutea. Staining intensity for both differed between all follicle sizes and was greatest (P < 0.01)in antral follicles. Staining for Kp10 and Kiss1r was similar in preantral follicles of all reproductive states but was greater (P < 0.01) than primordial follicles. In primordial follicles, staining for Kp10 and Kiss1r was greatest (P < 0.01) in ECP-sulpiride stimulated ovaries, but similar between all other states. Kisspeptin-10 and Kiss1r staining was greatest (P < 0.01) in antral follicles of FP and ECP-sulpiride stimulated ovaries. Additional quantification of Kp10 and Kiss1r immunostaining in granulosa cells (GC) of antral follicles was achieved by evaluating three random, 625 μm² fields in 2-3 follicles per animal in each reproductive state. Color deconvolution of standardized images was performed, and units of intensity converted to optical density and compared by ANOVA. Staining for both Kp10 and Kiss1r was most intense in GC of FP and ECP-sulpiride-stimulated ovaries and was greater (P < 0.0001) than LP and SA ovaries. No differences were detected between LP and SA. Here we characterize, for the first time, Kp10 and Kiss1r in the equine ovary. Staining intensity for both increased as follicle size increased. Staining was greatest in GC of FP ovaries, indicating a potential mechanistic role for kisspeptin during late-stage follicle growth and perhaps ovulation. Furthermore, staining in ECP-sulpiride stimulated ovaries was similar to FP ovaries, providing evidence that treatment with ECP-sulpiride during seasonal anovulation restored ovarian kisspeptin activity to a FP-like state.
Keywords	absorbance ; anovulation ; color ; estradiol ; horses ; hypothalamus ; immunohistochemistry ; kisspeptin ; normal distribution ; oocytes ; veterinary medicine ; winter
Language	English
Dates of publication	2023-06
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	2102631-2
ISSN	1542-7412 ; 0737-0806
ISSN (online)	1542-7412
ISSN	0737-0806
DOI	10.1016/j.jevs.2023.104713
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Article: Sucrose Acetate Isobutyrate (SAIB) as a Delivery Vehicle for Estradiol and Sulpiride: Evaluation of Endocrine Responses in Geldings and Ovarian Response in Seasonally Anovulatory Mares

Oberhaus, Erin L. / Wilson, Kaitlyn M. / Camp, Caroline M. / Sones, Jenny L.

Journal of equine veterinary science. 2022 May, v. 112

2022

Abstract	Sulpiride in vegetable shortening (VS) stimulates prolactin in horses for up to 10 days. Although effective, a pharmaceutical grade vehicle is needed for clinical application of sulpiride in horses. Sucrose acetate isobutyrate (SAIB), a hydrophobic polymer, may be an alternative to VS. Four in vivo experiments assessed the efficacy of SAIB for delivery of sulpiride, estradiol cypionate (ECP), and estradiol benzoate (EB). The first three studies utilized geldings to compare prolactin and luteinizing hormone (LH) concentrations between sulpiride delivered in VS and SAIB, and ECP or EB delivered in SAIB. Sulpiride stimulated (P < .01) prolactin similarly between vehicles. Geldings pretreated with EB had higher (P < .05) prolactin responses to sulpiride compared to ECP-treated geldings on days 5, 6 and 9. Both estradiol-sulpiride treatments stimulated LH with no differences between ECP and EB. Experiment 3 compared a simultaneous injection of EB-sulpiride to a non-simultaneous injection (one day apart) of EB-sulpiride. Prolactin was stimulated (P < .05) in both treatment groups, but the response lasted 2 days longer in geldings treated a day apart. Plasma LH increased (P < .01) in both groups equally for 10 days. Experiment 4 applied simultaneous and non-simultaneous EB-sulpiride treatments to seasonally anovulatory mares to induce ovarian activity. Prolactin and LH were stimulated similarly between treatments; however, non-simultaneously treated mares tended (P = .07) to have an ovarian response earlier. In conclusion, SAIB was a suitable vehicle for administration of estradiol and sulpiride and could be an alternative to VS for sustained-release drug delivery.
Keywords	acetates ; anovulation ; drugs ; estradiol ; hydrophobicity ; luteinizing hormone ; polymers ; prolactin ; sucrose ; vegetables ; veterinary medicine
Language	English
Dates of publication	2022-05
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2102631-2
ISSN	1542-7412 ; 0737-0806
ISSN (online)	1542-7412
ISSN	0737-0806
DOI	10.1016/j.jevs.2022.103896
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Article ; Online: Endocrine and ovarian responses to combined estradiol benzoate-sulpiride in seasonally anovulatory mares treated with kisspeptin.

Bailey, Victoria N / Sones, Jennifer L / Camp, Caroline M / Gomes, Viviane C L / Oberhaus, Erin L

Animal reproduction science

2022 Volume 247, Page(s) 107087

Abstract: The objective of this experiment was to determine if incorporation of kisspeptin-10 (Kp10) into treatment with estradiol benzoate (EB) and sulpiride to induce early cyclicity would result in greater endocrine responses and a greater number of mares ... ...

Abstract	The objective of this experiment was to determine if incorporation of kisspeptin-10 (Kp10) into treatment with estradiol benzoate (EB) and sulpiride to induce early cyclicity would result in greater endocrine responses and a greater number of mares responding with either follicle(s) > 30 mm or ovulation within 25 days of treatment. Eighteen anestrous mares were blocked by breed, body condition, and age before random assignment to treatment or control. All mares received 50 mg EB before receiving osmotic minipumps containing either saline (n = 9) or Kp10 (50 μg/hour; n = 9) one day later. The next day, all mares received 3 g sulpiride. Serial blood sampling occurred after pump placement and continued daily for 25 days. Transrectal ultrasounds were performed regularly to monitor ovarian activity. Data were analyzed by Student's t-test or ANOVA with repeated measures. Seven Kp10-treated mares responded compared to only 4 saline-treated mares. Mean days from sulpiride treatment to ovarian response was less in Kp10-treated mares (13.7 ± 1.1 d, P ≤ 0.01) compared to saline-treated mares (35.9 ± 7.8 d). Plasma prolactin increased (P < 0.001) in response to sulpiride in all mares; however, prolactin was higher (P < 0.05) in Kp10-treated mares. Plasma LH increased in all mares beginning 5 days after sulpiride but was greater (P < 0.0001) in Kp10-treated mares. Plasma FSH concentrations did not differ between groups. In conclusion, incorporation of Kp10 potentiated the prolactin and LH responses to EB-sulpiride and resulted in more mares responding with early ovarian activity.
Language	English
Publishing date	2022-09-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	429674-6
ISSN	1873-2232 ; 0378-4320
ISSN (online)	1873-2232
ISSN	0378-4320
DOI	10.1016/j.anireprosci.2022.107087
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Article ; Online: Metagenomic characterization of the equine endometrial microbiome during anestrus

Heil, Babiche A / van Heule, Machteld / Thompson, Sadie K / Kearns, Tabitha A / Beckers, Kalie F / Oberhaus, Erin L / King, Gary / Dini, Pouya / Sones, Jennifer L

Journal of Equine Veterinary Science. 2023 June, v. 125 p.104718-

2023

Abstract: Recent studies have confirmed that healthy uteri, including the equine uterus, harbour a microbiome. Studies on mares have been performed in estrus and therefore under the influence of high estrogen concentrations. Multiple human studies investigating ... ...

Abstract	Recent studies have confirmed that healthy uteri, including the equine uterus, harbour a microbiome. Studies on mares have been performed in estrus and therefore under the influence of high estrogen concentrations. Multiple human studies investigating the vaginal, as well as the gut microbiome have shown that the microbiome is dynamic throughout the estrous cycle and is influenced by differences in estrogen levels. This is in contrast to a study performed on Arabian mares which indicated that the equine vaginal microbiome is stable throughout the estrous cycle.In this study the resident uterine microbiome of healthy anestrous mares was characterized by metagenomics from double-guarded endometrial swabs and compared to the microbiome in the same mares during estrus.Double guarded endometrial swabs from 15 healthy estrous mares were taken and stored at -80°C until extraction, in the following non-breeding season 8 mares from this group were sampled in similar fashion during anestrus. Blank samples were obtained during both sample period. Genomic DNA was extracted using Qiagen DNeasy PowerSoil extraction kits and 16S rRNA gene was amplified using primers 515f-806r. An amplicon sequence variant table was made and chimeras were removed and the genomic16S rRNA from the blank samples was substracted. Sequences were processed and analysed using 16S rRNA SILVA v138.1 database. Contaminating reads were removed from the samples by subtracting the reads from the blank samples using Microdecon and downstream analysis performed using the Phyloseq package. Alpha and beta diversity were calculated using microbiome, amplicon and vegan packages.Results suggest that the equine uterine microbiome in estrus has a low diversity, low richness, and a low abundance at phylum level. The equine uterine microbiome in anestrus has a higher diversity, higher richness, and higher abundance compared to the estrus uterine microbiome. However, both the estrus as well as the anestrus endometrial microbiome is dominated by Proteobacteria, Firmicutes, and Bacteroidota. PCoA analysis displays a strong dissimilarity between estrus and anestrus samples.The difference in the microbiome between estrus and anestrus can possibly be explained due to the variance in immune responsiveness of the endometrium. The estrous mare's endometrium is under the influence of estrogens, allowing for a high immune response and possibly less diverse microbiome.
Keywords	DNA ; Firmicutes ; Proteobacteria ; anestrus ; databases ; endometrium ; estrogens ; estrus ; genes ; humans ; immune response ; intestinal microorganisms ; mares ; metagenomics ; microbiome ; species diversity ; variance ; vegan diet ; veterinary medicine
Language	English
Dates of publication	2023-06
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	2102631-2
ISSN	1542-7412 ; 0737-0806
ISSN (online)	1542-7412
ISSN	0737-0806
DOI	10.1016/j.jevs.2023.104718
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Article: Effects of Bromocriptine on Glucose and Insulin Dynamics in Normal and Insulin Dysregulated Horses.

Loos, Caroline M M / Urschel, Kristine L / Vanzant, Eric S / Oberhaus, Erin L / Bohannan, Adam D / Klotz, James L / McLeod, Kyle R

Frontiers in veterinary science

2022 Volume 9, Page(s) 889888

Abstract: The objectives of the study were to study the effects of the synthetic ergot alkaloid (EA), bromocriptine, on glucose and lipid metabolism in insulin dysregulated (ID, ...

Abstract	The objectives of the study were to study the effects of the synthetic ergot alkaloid (EA), bromocriptine, on glucose and lipid metabolism in insulin dysregulated (ID,
Language	English
Publishing date	2022-05-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2022.889888
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Article: Melanocyte-Stimulating Hormone Response to Exercise, Twitching, Epinephrine Injection, Substance P Injection, and Prostaglandin-F

Thompson, Donald L / Valencia, Nicole Arana / Walker, Neely L / Oberhaus, Erin L

Journal of equine veterinary science

2019 Volume 77, Page(s) 114–120

Abstract: Five experiments were performed to test the hypothesis that α-melanocyte-stimulating hormone (MSH) is secreted in response to various stressors in horses similar to prolactin, growth hormone, and adrenocorticotropin (ACTH). There was considerable ... ...

Abstract	Five experiments were performed to test the hypothesis that α-melanocyte-stimulating hormone (MSH) is secreted in response to various stressors in horses similar to prolactin, growth hormone, and adrenocorticotropin (ACTH). There was considerable variation in resting concentrations of MSH and in the degree of stimulation in responders; thus all data sets were tested for heterogeneity of variance and corrected for as needed before analysis. In experiment 1, 12 mares were used in a switchback design to test the effect of a 2-minute exercise bout on MSH secretion. Plasma MSH concentrations were constant when mares were not exercised but increased (P < .05) immediately (2 minutes) after exercise and were still elevated 5 minutes later. In experiment 2, six mares were twitched for 2 minutes and six mares were not twitched. Twitching stimulated (P < .05) both MSH and ACTH relative to controls. Experiments 3, 4, and 5 tested the acute effects of intravenous injection of epinephrine at 5 μg/kg of body weight, intravenous injection of 100 μg substance P, and intramuscular injection of 10 mg prostaglandin-F
MeSH term(s)	Adrenocorticotropic Hormone ; Animals ; Epinephrine ; Female ; Growth Hormone ; Horses ; Melanocyte-Stimulating Hormones ; Substance P
Chemical Substances	Substance P (33507-63-0) ; Adrenocorticotropic Hormone (9002-60-2) ; Growth Hormone (9002-72-6) ; Melanocyte-Stimulating Hormones (9002-79-3) ; Epinephrine (YKH834O4BH)
Language	English
Publishing date	2019-03-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2102631-2
ISSN	1542-7412 ; 0737-0806
ISSN (online)	1542-7412
ISSN	0737-0806
DOI	10.1016/j.jevs.2019.03.002
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Article: Effects of Epinephrine, Detomidine, and Butorphanol on Assessments of Insulin Sensitivity in Mares.

Kerrigan, Lauren E / Thompson, Donald L / Chapman, Ann M / Oberhaus, Erin L

Journal of equine veterinary science

2019 Volume 85, Page(s) 102842

Abstract: Sympathoadrenal stimulation may perturb results of endocrine tests performed on fractious horses. Sedation may be beneficial; however, perturbation of results may preclude useful information. Four experiments were designed to 1) determine the effects of ... ...

Abstract	Sympathoadrenal stimulation may perturb results of endocrine tests performed on fractious horses. Sedation may be beneficial; however, perturbation of results may preclude useful information. Four experiments were designed to 1) determine the effects of epinephrine on insulin response to glucose (IR2G), 2) assess the effects of detomidine (DET), alone or combined with butorphanol (DET/BUT), on IR2G and glucose response to insulin (GR2I), and 3) assess the effects of BUT alone on IR2G. In Experiment 1, mares were administered saline or epinephrine (5 μg/kg BW) immediately before infusion of glucose (100 mg/kg BW). Glucose stimulated (P < .05) insulin release in controls at 5 minutes that persisted through 30 minutes; insulin was suppressed (P < .05) by epinephrine from 5 to 15 minutes, rising gradually through 30 minutes. Experiments 2 (IR2G) and 3 (GR2I) were conducted as triplicated 3 × 3 Latin squares with the following treatments: saline (SAL), DET, and DET/BUT (all administered at .01 mg/kg BW). Glucose stimulated (P < .05) insulin release that persisted through 30 minutes in SAL mares; DET and DET/BUT severely suppressed (P < .0001) the IR2G. Sedation did not affect resting glucose and had inconsistent effects on the GR2I when mares were treated with 50 mIU/kg BW recombinant human insulin. Butorphanol had no effect on IR2G. In conclusion, adrenergic agonists severely suppress the IR2G and cannot be used for sedation for this test. The use of DET did not alter the GR2I, and therefore may be useful for conducting this test in fractious horses.
MeSH term(s)	Animals ; Butorphanol ; Cross-Over Studies ; Epinephrine ; Female ; Horse Diseases ; Horses ; Imidazoles ; Insulin Resistance
Chemical Substances	Imidazoles ; detomidine (7N8K34P2XH) ; Butorphanol (QV897JC36D) ; Epinephrine (YKH834O4BH)
Language	English
Publishing date	2019-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2102631-2
ISSN	1542-7412 ; 0737-0806
ISSN (online)	1542-7412
ISSN	0737-0806
DOI	10.1016/j.jevs.2019.102842
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