Prolactin in the Horse: Historical Perspective, Actions and Reactions, and Its Role in Reproduction

© 2015 Elsevier Inc. Prolactin is a hormone with diverse biological effects in various species. The secretion of prolactin in horses is affected by season, thyrotropin-releasing hormone, dopaminergic and antidopaminergic agents, exercise and stressful stimuli, meal feeding, estrogen treatment, and antiopioidergic agents. The need of prolactin for mammary growth and lactation in mares has been elucidated from research on endophyte-infected fescue grazing and its associated problems in late gestation. This has led to the development of treatments for fescue toxicity and protocols for inducing lactation in nonpregnant mares. Treatment with prolactin has demonstrated that it is involved with the shedding of the winter coat in spring (increasing concentrations) and likely with the growth of the winter coat in the fall (decreasing concentrations). Prolactin secretion is highly correlated with the photoperiod and is low in winter and high in summer. The coincidence of rising prolactin concentrations in blood with the onset of ovarian activity during the spring transition period in mares led to research showing that prolactin treatment, or inducement of high prolactin secretion by means of antidopaminergic agents, in winter can induce ovarian activity and ovulation in seasonally anovulatory mares. The combination of a small amount of estrogen in addition to an antidopaminergic agent has been shown to produce a synergy resulting in very high prolactin concentrations in blood. The results of 39years of research on equine prolactin illustrate nicely how the gradual accumulation of knowledge derived from basic research questions can generate applied solutions to real-world problems

Effect of Repeated Cabergoline Treatment on the Vernal Transition and Hair Shedding of Mares (Year 1) and a Subsequent Comparison of the Effect of Starting Date on Prolactin Suppression (Year 2)

© 2016 Elsevier Inc. Two studies were conducted to determine efficacy of cabergoline for suppressing prolactin (PRL) and the possible effects on vernal transition in mares. In experiment 1, six mares each received either vehicle or cabergoline (5 mg, intramuscularly) every 10 days for 12 treatments beginning February 4, 2013. Blood samples were drawn regularly, and mares were challenged with sulpiride periodically to assess PRL suppression. Weekly hair samples were obtained to determine shedding. Prolactin was suppressed (P \u3c .05) by cabergoline, but suppression waned in spring. There was no effect (P \u3e .05) of treatment on day of first ovulation, luteinizing hormone, or follicle stimulating hormone. Hair shedding was generally suppressed (P = .05). In 2014 (experiment 2), eight of the same 12 mares were used in a similar experiment to determine if the rise in PRL observed in experiment 1 was due to refractoriness to cabergoline or perhaps another factor. Treatment began on April 6, 2014, corresponding to the increase in PRL in treated mares in experiment 1. Mares were treated with cabergoline or vehicle until June 5. Prolactin was suppressed (P \u3c .05) by cabergoline, and the pattern of apparent escape from suppression was similar to year 1. We conclude that (1) cabergoline at this dose alters hair shedding but does not alter the time of first ovulation in mares and (2) relative to our previous reports of cabergoline treatment in the fall, there is a seasonal effect on the ability of this dose of cabergoline to suppress unstimulated PRL secretion

Responses of Adenohypophyseal Hormones to Substance P Administration in Geldings: Comparison to Responses After Brief Exercise and Sulpiride Administration

© 2016 Elsevier Inc. Nine adult geldings were used in three experiments to study the possible role of substance P in the prolactin responses to nondopaminergic stimuli. Experiment 1 was performed as an incomplete Latin square design to determine the secretory responses of prolactin, growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to IV administration of substance P. Doses tested and compared to no peptide (0 dose, control) were 62, 125, 250, and 500 μg of substance P. The three highest doses of peptide caused an immediate rise in heart rate, sweating, salivation, rhinorrhea, stretching of hind legs, and defecation. The lowest dose (62 μg) caused minor sweating, some rhinorrhea, and a rise in heart rate. Recovery from these physical responses was complete in approximately 30 minutes. All doses of substance P caused an immediate rise (P \u3c .01) in plasma prolactin concentrations, with the three highest doses producing similar responses, and the 62 μg dose producing a minimal response (P \u3c .05). Concentrations of ACTH (P \u3c .01) and GH (P = .05) also increased after substance P administration; concentrations of LH, FSH, and TSH were unaffected. Experiment 2 compared the effects of brief exercise on hormonal characteristics. Two minutes of trotting increased (P \u3c .01) plasma concentrations of GH, ACTH, and prolactin, as well as LH (P = .055). Experiment 3 determined the relative responses of prolactin to a fixed dose of sulpiride (0.1 mg/kg of body weight). In general, the prolactin responses to substance P were similar to those after exercise, which were both generally less than after sulpiride. These data are consistent with a possible role of substance P in the prolactin response to stressful stimuli

Melanocyte-Stimulating Hormone Response to Exercise, Twitching, Epinephrine Injection, Substance P Injection, and Prostaglandin-F \u3csub\u3e2α\u3c/sub\u3e Administration in Mares

© 2019 Elsevier Inc. 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 \u3c.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 \u3c.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 2α in mares compared to controls (6, 5, and 6 mares per treatment group, respectively). Concentrations of MSH increased (P ≤.05) after treatment in all three experiments. Plasma concentrations of ACTH also increased (P \u3c.01) after administration of epinephrine and prostaglandin-F 2α in experiments 3 and 5; plasma ACTH was not measured in experiment 1 or 4 because we have previously reported that exercise and substance P stimulate plasma ACTH concentrations. As hypothesized, MSH is secreted in response to various stimuli similar to that observed previously for prolactin, growth hormone, and ACTH

Immunohistochemical localization of prolactin receptors within the equine ovary

© 2015 Elsevier Inc. Prolactin (PRL) is hypothesized to stimulate follicular growth through a physiological action at the ovary. Immunohistochemistry was used to identify PRL receptors (PRLrs) within the equine ovary. Prolactin receptors were detected in anestrous (n = 3), winter cycling (n = 2), summer follicular (n = 3), and luteal phase (n = 3) ovaries. Prolactin receptors were detected in follicles of all stages, in corpus luteum and on oocytes. Staining intensity did not differ (P \u3e .05) between primordial and preantral follicles but was greater (P \u3c .001) in antral follicles than in primordial or preantral follicles. Greater PRLr staining (P \u3c .001) occurred in winter cycling primordial follicles (1.58 ± 0.09) than anestrous (0.67 ± 0.10) and summer luteal phase primordial follicles (1.16 ± 0.12; P \u3c .01) but not in primordial follicles during the summer follicular phase (P \u3e .05). Prolactin receptor staining in preantral follicles during anestrus was lower (P \u3c .05) than for all other reproductive states. Winter cycling and summer luteal phase preantral follicles stained most intensely, and both had greater PRLr staining than preantral follicles from anestrous ovaries (P \u3c .001) or summer follicular phase ovaries (P \u3c .001). Prolactin receptor staining of antral follicles was the most intense of all follicular sizes and did not vary (P \u3e .10) between reproductive states. Prolactin receptor staining was also detected in luteal tissue. In conclusion, PRLrs were detected in all stages of follicular growth with staining intensity highest in large antral follicles, indicating a possible mechanistic role for PRL during late stage follicular growth and perhaps ovulation

Dopaminergic and Antidopaminergic Effects on Heart Rate in Healthy Horses When Challenged With Brief 2-minute Exercise Bouts

© 2018 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 \u3c.05) the exercise-induced rise in HR and the ACTH and GH responses (P \u3c.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

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

© 2016 Elsevier Inc. 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 \u3e .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