Nicole Arana Valencia

Effects of Various Methods of Sulpiride Administration on Prolactin Release in Horses

Abstract Four experiments assessed factors affecting prolactin responses to sulpiride administration in horses. Experiment 1 compared the efficacy of the (−) enantiomer of sulpiride to that of the commonly used (+/−) racemic mixture. Mares were used in an 8 × 8 Latin square to compare the prolactin responses to four doses of levosulpiride to four corresponding doses of the racemic mixture at twice the dose. Responses at each dose indicated equal and similar (P > .1) responses. Experiment 2 compared the efficacy of 1 gram of orally administered racemic sulpiride to 100 mg of intramuscularly injected sulpiride in oil in mares primed with 50 mg of estradiol cypionate (ECP). Prolactin responses in groups receiving sulpiride were robust but similar in magnitude with minor differences in timing. In experiment 3, ECP‐primed geldings received subcutaneous injections of 1.8 grams racemic sulpiride in vegetable shortening in one of three sites: the neck, the back below the withers, or the lower girth region; control geldings received no sulpiride. Prolactin responses to sulpiride lasted a minimum of 96 hours. In experiment 4, prolactin responses to 3 g of racemic sulpiride in vegetable shortening were compared to similar injections (3 g) in 5 mL of sucrose acetate isobutyrate (SAIB; SucroMate) or just SAIB (control) in ECP‐primed geldings. Controls had no prolactin response to SucroMate, whereas both treatment groups had extended prolactin responses lasting at least 10 days. It is concluded that prolactin responses to sulpiride in horses can be greatly extended by using hydrophobic vehicles like vegetable shortening or SAIB. HighlightsThe antidopaminergic activity of the (−) enantiomer of sulpiride by weight on prolactin secretion is approximately twice that of the (+/−)‐racemic mixture, confirming that the (−) enantiomer is the active component of the racemic mixture.Sulpiride administered orally had approximately one‐tenth the antidopaminergic activity of sulpiride administered intramuscularly in oil.Administration of 1.8 grams of sulpiride in vegetable shortening to estrogen‐primed geldings extended the stimulatory effect on prolactin secretion to a minimum of 96 hours.Intramuscular administration of 3 grams of sulpiride in sucrose acetate isobutyrate vehicle, in the form of SucroMate, extended the stimulatory effect on prolactin secretion to approximately 10 days.Prolactin responses to sulpiride in horses can be greatly extended by using hydrophobic vehicles like vegetable shortening or sucrose acetate isobutyrate.

Thyrotropin-Releasing Hormone: A Powerful Tripeptide With Diverse Effects in Horses

Abstract Thyrotropin‐releasing hormone (TRH) was the first trophic “factor” from the hypothalamus to be isolated and identified chemically. It was known to have a stimulatory effect on thyroid‐stimulating hormone (TSH) production and secretion by cells within the adenohypothesis, and its structure was revealed to be a modified tripeptide: (pyro)Glu‐His‐Pro‐NH2. Intravenous or intramuscular injection of TRH to horses results in an immediate rise in plasma TSH concentrations, as would be expected. However, it is now known that TRH has consistent effects on four of the other five cell types in the equine adenohypophysis as well. Administration of TRH to horses stimulates not only plasma TSH concentrations, but also plasma prolactin, adrenocorticotropic hormone, and melanocyte‐stimulating hormone concentrations. In contrast, administration of TRH simultaneously or within 1 hour before administration of secretagogues for growth hormone (GH) greatly reduces the GH response to the secretagogues. To date, TRH has not been reported to have positive or inhibitory effects on the release of luteinizing hormone or follicle‐stimulating hormone from gonadotropes. Whether the noted effects of TRH on cells other than the thyrotropes are physiologic or pharmacologic is not clear. Regardless, a significant clinical utility has developed for the use of TRH in diagnosing thyroid gland disease as well as pituitary pars intermedia dysfunction in horses. HighlightsThyrotropin‐releasing hormone was the first trophic “factor” from the hypothalamus to be isolated and identified chemically.Thyrotropin‐releasing hormone is a known regulator of thyroid‐stimulating hormone production and secretion in the adenohypophysis with the structure (pyro)Glu‐His‐Pro‐NH2.Thyrotropin‐releasing hormone also has stimulatory effects on secretion of prolactin, adrenocorticotropin, and melanocyte‐stimulating hormone from the adenohypophysis.Thyrotropin‐releasing hormone in some way inhibits the normal growth hormone (GH) response to various GH secretagogues but does not have any effect on secretion of luteinizing hormone or follicle‐stimulating hormone.This diversity of effects has been extensively applied in research as well as in clinical settings in diagnostic tests for thyroid dysfunctions and pituitary pars intermedia dysfunction.

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.