E.L. Oberhaus

Factors Affecting the Ovarian Response to a Combined Estradiol-Sulpiride Treatment in Seasonally Anovulatory Mares

Abstract Twenty‐three seasonally anovulatory mares, housed at two separate farms, were treated with 50 mg of estradiol cypionate (ECP) and 3 g of sulpiride in January to study factors that contributed to success of the treatment (response = ovulation within 28 days). Every other day, blood samples and pretreatment secretagogue challenges were used to characterize prolactin, luteinizing hormone (LH), insulin‐like growth factor‐I, leptin, and insulin concentrations. Ovaries of each mare were scanned via ultrasound regularly until detection of a 32–35 mm follicle, at which time the mare was artificially inseminated. Prolactin was stimulated in all treated mares and was similar (P > .05) in responding and nonresponding mares. Nine mares, all at the same farm (Ben Hur; farm effect, P = .006), responded with preovulatory sized follicles within 20 days of treatment. Five of the 9 were inseminated and 3 conceived. Retrospective analysis revealed that of the mares responding, body condition score (P = .03), body weight (P = .02), plasma concentrations of insulin (P = .01) and leptin (P = .09), and pretreatment response of LH to gonadotropin‐releasing hormone (P = .106) were higher in responding than in nonresponding mares. In general, factors that differed and may contribute to whether a given mare responds to this ECP‐sulpiride protocol were mainly characteristics pointing toward well‐nourished mares. Minor nutritional differences between farms likely played a role in the lack of success on the one farm. Also, the LH response to gonadotropin‐releasing hormone prior to treatment may be indicative of the subsequent LH response to ECP‐sulpiride and hence the ovarian response. HighlightsCombined estradiol cypionate (ECP) and sulpiride hastens vernal transition in some mares.Nutritional status contributes to early ovulation post–ECP‐sulpiride treatment.Mares ovulating early had higher leptin, insulin, and body condition scores.Luteinizing response to gonadotropin‐releasing hormone as well as to ECP likely contributes to early ovulation.

Dopaminergic and antidopaminergic effects on heart rate in healthy horses when challenged with brief 2-minute exercise bouts

ABSTRACT Bromocriptine is a dopamine receptor agonist known to cause hypotension and bradycardia in several species. Five experiments were conducted to compare possible perturbations on heart rate (HR) in horses after a brief (2 minutes) exercise bout when exposed to either short‐term or long‐term treatment with bromocriptine, cabergoline, or pergolide (all commonly used dopaminergic agonists in horses) or sulpiride, a dopaminergic antagonist. For all experiments, prolactin was measured as an indicator of drug efficacy. Experiments 1 and 4 were conducted as a replicated Latin square, whereas experiments 2, 3, and 5 were double split plot designs. Experiment 1 tested changes in HR, adrenocorticotropin (ACTH), and growth hormone (GH) concentrations when geldings were pretreated with 50 mg of bromocriptine 12 hours before exercise. Bromocriptine pretreatment reduced (P < .05) the exercise‐induced rise in HR and the ACTH and GH responses (P < .05). Experiment 2 assessed the daily responses of HR to exercise after intramuscular administration of 5 mg of cabergoline in vegetable oil, which diminished the rise in HR because of exercise for the first 2 days of the 7‐day experiment. In experiment 3, daily feeding of 2g of pergolide top dressed over sweet feed had no effect on HR in response to exercise. Similar results were seen in experiments 4 and 5, when horses were intravenously administered .01 mg/kg BW sulpiride in saline or intramuscularly administered 1g of sulpiride dissolved in vegetable oil. Taken together, bromocriptine and cabergoline, but not pergolide or sulpiride, dampened the cardiac sympathetic response to exercise, thus, lowering the HR. HIGHLIGHTSACTH and GH responses to exercise were dampened due to bromocriptine administration.Bromocriptine and cabergoline had bradycardic effects after a brief exercise bout.Pergolide nor sulpiride administration affected the heart rate response to exercise.

Effects of Combined Estradiol-Sulpiride Treatment and Follicle Ablation on Vernal Transition in Mares: Evaluation of Plasma and Follicular Fluid Hormones and Luteinizing Hormone Receptor Gene Expression

&NA; This experiment assessed the hormonal production, secretory aspects, and changes in luteinizing hormone (LH) receptor gene expression of early induced ovulatory‐sized follicles relative to the first ovulatory‐sized follicles occurring naturally in the spring. Anovulatory mares were treated on January 21 with (1) 50 mg of estradiol cypionate (ECP, n = 8) alone or (2) with ECP followed by two 3‐g sulpiride injections (n = 8), 5 and 12 days later. Half of each group also received complete follicle ablation via transvaginal aspiration before ECP treatment. Ovaries were scanned regularly until detection of a 32–35 mm follicle; follicular fluid was recovered via aspiration for analysis of hormonal concentrations. Blood was collected regularly to characterize plasma prolactin, LH, follicle stimulating hormone, progesterone, and estradiol concentrations. Mean date to first 35‐mm follicle was earlier (P < .05) in sulpiride‐treated mares: five of eight (63%) responded within 28 days of the first sulpiride injection. Ablation did not affect ovarian response. Plasma prolactin was stimulated (P < .0001) in ECP‐sulpiride–treated mares for 16 days but did not dictate ovarian response. Estradiol stimulated plasma LH (P < .05), which was higher (P < .05) in treated mares that responded. There was no effect of treatment or ablation on follicular fluid concentrations of estradiol, progesterone, leptin, or insulin‐like growth factor 1 or on LH receptor gene expression. These latter similarities indicate that ECP‐sulpiride early induced follicles have apparently reached a degree of maturity equivalent to naturally occurring ovulatory‐sized follicles later in the spring.

Seasonal Assessment of Duration of Prolactin Suppression Following Cabergoline Treatment in Mares: Unstimulated Versus Sulpiride and Thyrotropin-Releasing Hormone-Stimulated Responses

Abstract Experiments 1 through 4 were performed to test the hypothesis that season affects the duration of prolactin suppression by a single injection of the dopaminergic agonist, cabergoline. In each, six mares received cabergoline intramuscularly and four received the vehicle. The protocol was repeated around the vernal equinox, summer solstice, autumnal equinox, and winter solstice. In all experiments, cabergoline suppressed (P < .01) prolactin for at least 5 days; concentrations in fall and winter were naturally low; thus, treatment effects were harder to detect. Experiments 5 and 6 tested whether basal (unstimulated) prolactin concentrations recovered from cabergoline suppression faster (earlier) than secretagogue‐induced prolactin secretion. In July, five mares each were treated with either compounded cabergoline or cabergoline in oil; four others received oil. Cabergoline suppressed (P < .0001) prolactin in both treated groups for approximately 6 days. Prolactin in daily samples returned to control levels thereafter, whereas low‐dose sulpiride‐stimulated secretion remained suppressed by >50% at 11 days after treatment. In the last experiment, treatment with cabergoline or oil (n = 6 mares each) in October followed by thyrotropin‐releasing hormone (TRH) challenges resulted in similar responses to those in experiment 5; TRH‐induced prolactin responses were still suppressed (P < .05) on day 11. In conclusion, little seasonal variation in duration of prolactin suppression in response to cabergoline was detected. In general, secretagogue‐induced secretion is suppressed much longer than basal secretion. This dichotomy may indicate at least two subpopulations of lactotropes regulated differentially by dopamine input. HighlightsCabergoline suppressed prolactin for approximately 5 days, regardless of season.No evidence of seasonal variation in recovery of prolactin in response to cabergoline was found.Prolactin response to sulpiride or thyrotropin‐releasing hormone remained suppressed in cabergoline‐treated mares for 11 days.

Long-term and Short-term Dopaminergic (Cabergoline) and Antidopaminergic (Sulpiride) Effects on Insulin Response to Glucose, Glucose Response to Insulin, or Both in Horses

Abstract Dopaminergic drugs, such as those used to treat pituitary pars intermedia dysfunction (PPID) in horses, have been shown to improve insulin sensitivity in other species. It has been suggested that pergolide, used to treat PPID, may enhance insulin sensitivity in resistant horses, although evidence for that remains unclear. Four experiments were conducted herein to determine possible effects of dopaminergic inhibition or stimulation on two indices of insulin sensitivity in horses: the glucose response to insulin (GR2I), administered intravenously (IV) using a fixed dose of recombinant human insulin, and the insulin response to an acute IV infusion of glucose (IR2G). The first experiment tested the short‐term effects of sulpiride (in saline; IV) 5 minutes prior to IR2G in insulin‐sensitive and insulin‐insensitive mares. Experiment 2 tested the effects of a long‐term sulpiride protocol (1.5 g intramuscularly [IM] every 5 days for 45 days) on GR2I and IR2G in insulin‐sensitive and insulin‐insensitive geldings. Experiment 3 tested the short‐term effects of 5‐mg cabergoline IM on GR2I and IR2G in insulin‐sensitive and insulin‐insensitive mares. The fourth experiment tested the long‐term effects of cabergoline IM on GR2I in insulin‐sensitive mares. Results from these experiments revealed that neither increased nor decreased dopaminergic activity, in the long or short term, had any impact on GR2I or IR2G in horses (P > .1), regardless of starting insulin sensitivity status. We conclude that dopaminergic agents have no benefit for treating insulin insensitivity in horses, in spite of a perception of such benefits permeating the industry. HighlightsDopaminergic action on insulin sensitivity was studied.Prolactin was used to monitor activities of the treatments.Treatment with sulpiride did not affect insulin sensitivity.Treatment with cabergoline did not affect insulin sensitivity.Prolactin concentrations responded as expected to the treatment.