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Marine mammals are regularly reported as bycatch in commercial and artisanal fisheries, but data are often insufficient to allow assessment of these incidental mortalities. Observer coverage of the mackerel trawl fishery in New Zealand waters between 1995 and 2011 allowed evaluation of common dolphin Delphinus delphis bycatch on the North Island west coast, where this species is the most frequently caught cetacean. Observer data were used to develop a statistical model to estimate total captures and explore covariates related to captures. A two-stage Bayesian hurdle model was used, with a logistic generalised linear model predicting whether any common dolphin captures occurred on a given tow of the net, and a zero-truncated Poisson distribution to estimate the number of dolphin captures, given that there was a capture event. Over the 16-year study period, there were 119 common dolphin captures reported on 4299 observed tows. Capture events frequently involved more than one individual, with a maximum of nine common dolphin observed caught in a single tow. There was a peak of 141 estimated common dolphin captures (95% c.i.: 56 to 276; 6.27 captures per 100 tows) in 2002-03, following the marked expansion in annual effort in this fishery to over 2000 tows. Subsequently, the number of captures fluctuated although fishing effort remained relatively high. Of the observed capture events, 60% were during trawls where the top of the net (headline) was <40 m below the surface, and the model determined that this covariate best explained common dolphin captures. Increasing headline depth by 21 m would halve the probability of a dolphin capture event on a tow. While lack of abundance data prevents assessment of the impact of these mortalities on the local common dolphin population, a clear recommendation from this study is the increasing of headline depth to reduce common dolphin captures.

The nonergot alkaloid-producing endo-phyte, AR542, has been shown to improve the persistence and yield of tall fescue pastures without causing the animal disorders commonly associated with tall fescue toxicosis. A 3-yr grazing study was conducted to compare effects of AR542-infected tall fescue pastures with wild type endophyte-infected (E+) tall fescue pastures on cow-calf performance. Replicated 7.3-ha pastures of each treatment were grazed by cow-calf pairs (16 pairs per pasture replication) each year from March to weaning in September. The cows were exposed to breeding on their respective pasture treatments from April 1 through June 15. The treatment groups were compared for reproductive performance, ADG, BCS, calf growth rate, and weaning weight. Blood samples were also collected for serum prolactin (PRL) analysis. There were no significant differences in calving rate (P = 0.98) or calving interval (P = 0.62) between pasture treatments. Cows that grazed the AR542 pastures subsequently gave birth to calves that were heavier (P < 0.05) than calves from cows that had grazed the E+ pastures. Cows grazing the AR542 pastures had higher (P < 0.05) BCS at the end of the grazing period, and had higher ADG during the grazing period. Calves raised on the AR542 pasture had higher (P < 0.05) ADG and weaning weights than calves of the same sex raised on the E+ pastures. Serum PRL concentrations were decreased (P < 0.05) in both cows and calves on the E+ pastures compared with serum PRL concentrations in cows and calves grazing the AR542 pastures. The results indicate that grazing tall fescue pastures infected with the AR542 endophyte may give significant advantages in cow-calf growth rates and BCS over grazing E+ pastures. However, there did not seem to be any benefit in reproductive performance in this trial. There was a small, but significant increase in birth weight in cows grazing AR542 pasture.

Ergot alkaloids are considered causative agents of fescue toxicosis, a syndrome experienced by cattle consuming tall fescue (Festuca arundinacea) infected with the fungal endophyte Neotyphodium coenophialum. One sign of fescue toxicosis in cattle is severe hyperthermia. This study assessed hormonal responses to ergotamine in heat-sensitive and heat-tolerant cattle. Seven Hereford (heat-sensitive, Bos taurus) and 7 Brahman (heat-tolerant, Bos indicus) steers on a fescue-free diet received ergotamine tartrate iv. Blood was sampled every 15 min for 2 h before and 4 h after dosing for determination of circulating hormonal changes. Respiration rates were recorded hourly. Ambient temperature and relative humidity averaged 31C and 48%, respectively, during sampling. A breed x time interaction existed (p < 0.01) for plasma prolactin, LH, insulin, glucagon, cortisol, triiodothyronine and glucose concentrations. The breed x time interaction tended to affect (p = 0.14) growth hormone and influenced (p < 0.01) respiration rates. Ergotamine reduced (p < 0.01) plasma LH and increased (p < 0.01) growth hormone concentrations in Brahman. Both breeds responded to ergotamine with increased (p < 0.01) plasma cortisol, glucagon, and glucose and reduced (p < 0.01) insulin concentrations. The magnitude of response for cortisol, insulin, and glucose were greater for the Brahman. Ergotamine increased (p < 0.01) plasma triiodothyronine and respiration rates in Hereford, whereas these traits were unaltered in Brahman. Acute ergotamine exposure generally resulted in similar effects on Brahman and Hereford steers. The triiodothyronine and respiratory comparisons revealed modified responses in Brahman that suggest a potential benefit of using heat-tolerant genetics to reduce the adverse effects of fescue toxicosis in cattle.

The objective of this research was to determine if ergotamine, an ergopeptine alkaloid isolated from Neotyphodium-infected grasses and associated with toxicoses in livestock, altered plasma concentrations of reproductive hormones in follicular phase heifers and in cows given a progestin implant. In Experiment 1, blood was sampled for 8h from four cycling heifers 2 days after synchronized luteolysis. Heifers were treated with ergotamine tartrate (19microg/kg) i.v. or saline vehicle in a simple cross-over design after 1h of pre-treatment blood sampling. Heifers received oxytocin (100USP units) i.v. 4h after ergotamine or saline treatment. Ergotamine reduced (P<0.01) prolactin concentrations from 1 to 4h post-treatment and increased (P<0.01) 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) concentrations from 2 to 5h post-treatment. A PGFM response to oxytocin was not detected. In Experiment 2, blood was sampled for 8h from six cycling cows 10 days after receiving a s.c. norgestomet implant. Cows were treated i.v. with ergotamine (20microg/kg) or saline in a simple cross-over design after 1h of pre-treatment blood sampling. Cows received gonadorelin (GnRH, 100microg) i.v. 1h after ergotamine or saline. Cows received oxytocin (100USP units) i.v. 4h after ergotamine or saline treatment. Ergotamine reduced (P<0.01) serum prolactin concentrations by 120min after treatment, with prolactin returning to pre-treatment concentrations by 200min after treatment. Saline-treated cows had lower (P<0.01) prolactin by 280min after treatment. Ergotamine-treated cows had higher (P<0.01) PGFM concentrations compared to saline-treated cows 120-240min after treatments, but the groups exhibited similar increases in PGFM after oxytocin. Plasma LH and FSH concentrations increased to peaks 100-120min after GnRH for both groups. However, the LH response to GnRH was greater (P<0.01) for ergotamine-treated cows. In summary, ergotamine lowered prolactin and elevated PGFM concentrations in follicular phase heifers and cows on norgestomet therapy. Ergotamine increased the LH response to exogenous GnRH in cows with norgestomet implants. These data highlight the potential of ergopeptine alkaloids to affect reproduction through altered endocrine function.

Ergot alkaloids cause fescue toxicosis when livestock graze endophyte-infected tall fescue. It is generally accepted that ergovaline is the toxic component of endophyte-infected tall fescue, but there is no direct evidence to support this hypothesis. The objective of this study was to examine relative and potential transport of ergoline and ergopeptine alkaloids across isolated gastric tissues in vitro. Sheep ruminal and omasal tissues were surgically removed and placed in parabiotic chambers. Equimolar concentrations of lysergic acid, lysergol, ergonovine, ergotamine, and ergocryptine were added to a Kreb's Ringer phosphate (KRP) solution on the mucosal side of the tissue. Tissue was incubated in near-physiological conditions for 240 min. Samples were taken from KRP on the serosal side of the chambers at times 0, 30, 60, 120, 180, and 240 min and analyzed for ergot alkaloids by competitive ELISA. The serosal KRP remaining after incubation was freeze-dried and the alkaloid species quantified by HPLC. The area of ruminal and omasal tissues was measured and the potential transportable alkaloids calculated by multiplying the moles of transported alkaloids per square centimeter of each tissue type by the surface area of the tissue. Studies were conducted to compare alkaloid transport in reticular, ruminal, and omasal tissues and to determine whether transport was active or passive. Ruminal tissue had greater ergot alkaloid transport potential than omasal tissue (85 vs 60 mmol) because of a larger surface area. The ruminal posterior dorsal sac had the greatest potential for alkaloid transport, but the other ruminal tissues were not different from one another. Alkaloid transport was less among reticular tissues than among ruminal tissues. Transport of alkaloids seemed to be an active process. The alkaloids with greatest transport potential were lysergic acid and lysergol. Ergopeptine alkaloids tended to pass across omasal tissues in greater quantities than across ruminal tissues, but their transport was minimal compared to lysergic acid and lysergol.

The objective of this experiment was to investigate whether the ergot alkaloid, ergotamine (ET), an alkaloid used to model fescue toxicosis in cattle, modifies the response of cattle to endotoxin (LPS) challenge. Steers (n = 16) were divided into the following treatment groups: control (C), ergotamine (ET), endotoxin (LPS), and ET + LPS. ET and ET + LPS groups received a single bolus intravenous injection of ET (40 microg. kg. body wt(-1)), whereas C and LPS steers received a single bolus injection of sterile vehicle. Thirty minutes after ET/vehicle administration, a single bolus intravenous injection of LPS (0.2 microg. kg. body wt(-1)) was given. Blood was collected at various time points for 48 hr post. Endotoxin increased rectal temperature (RT) and the circulating levels of tumor necrosis factor-alpha (TNF-alpha), cortisol, haptoglobin (Hp), thromboxane B(2) (TXB(2)). The circulating Hp, TNF-alpha, and TXB(2) increases were blunted by pretreatment with ET compared with ET + LPS. Ergotamine by itself increased circulating cortisol and RT, whereas it decreased serum prolactin (PRL). Therefore, whereas administration of LPS at 0.2 microg/kg to steers resulted in an expected response, the combination of ET + LPS attenuated major effects of LPS alone. Thus, acute administration of ET appeared to be anti-inflammatory as it decreased the inflammatory response to LPS, an effect likely driven at least in part by the ET-caused cortisol increase.

Objective: To determine effects of an extract of Serenoa repens on dogs with prostatic hyperplasia., Animals: 20 mature male dogs with benign prostatic hyperplasia., Procedure: Dogs were assigned to 3 comparable groups on the basis of prostatic volume per kg of body weight and degree of prostatic hyperplasia determined histologically. Dogs in 2 groups were treated for 91 days (8 received 500 mg, PO, q 8 h [1,500 mg/d], and 6 received 100 mg, PO, q 8 h [300 mg/d]). The control group of 6 dogs did not receive medication. Effects of treatment on prostatic volume, prostatic weight, prostatic histologic characteristics, radiographic and ultrasonographic assessment of prostatic size, results of CBC, serum biochemical analyses, and urinalysis, serum testosterone concentration, and semen characteristics were determined. At the termination of the study, all dogs were euthanatized, and necropsies were performed. Investigators conducting tests and interpreting results were not aware of treatment group of each dog., Results: Treatment did not affect prostatic weight, prostatic volume, or prostatic histologic scores, libido, semen characteristics, radiographs of the caudal portion of the abdomen, prostatic ultrasonographs, or serum testosterone concentrations. Results of CBC, serum biochemical analyses or urinalysis, and body weights did not change during treatment., Conclusions and Clinical Relevance: Treatment with an extract of S repens for 91 days did not significantly affect the prostate gland of dogs. Adverse effects were not evident. Although products containing extracts of S repens are widely advertised for men with prostatic hyperplasia, beneficial or harmful effects of this plant extract were not found in dogs with prostatic hyperplasia.

Fescue toxicosis research studies have often included serum prolactin as a physiologic index of the disorder. Serum prolactin has not been used as a clinical measure of fescue toxicosis because of variation associated with sex and physiologic condition of the animal and climatic and seasonal factors. The primary excretory route of the alkaloids responsible for this toxicosis is the urine. Three pasture experiments were conducted to examine serum prolactin and urinary ergot alkaloid variability among steers continuously grazing endophyte-infected (E+) or endophyte-free (E-) tall fescue and among steers that were switched from one pasture form to the other. A fourth grazing experiment was used to examine how to best to manage the steers prior to sampling for urinary ergot alkaloid excretion. Coefficients of variability for urinary alkaloid excretion were consistently lower (46-65%) than serum prolactin (64-142%). Urinary alkaloid excretion patterns changed within 12 hours following switching steers from E+ to E- pasture or vice versa, but serum prolactin was recalcitrant to change. Because it is less variable and more dynamic than serum prolactin, urinary alkaloid excretion can be used for health assessment of steers grazing E+ and E- pastures. Regression analysis established a quadratic relationship between alkaloid excretion and average daily weight gain, with a regression coefficient of 0.86. Urinary alkaloid analysis was useful in determining whether cattle were consuming toxic tall fescue.

The ergopeptine alkaloid ergotamine (ET) mimics the effects of ergopeptine alkaloids found in endophyte-infected (E+) fescue forage considered causative for fescue toxicosis. Altered immune capacity, compromised intake and thermoregulation, and inflammatory changes are observed in fescue toxicosis. Taken together, these suggest the cytokine pattern may be altered by ergot alkaloids. Thus, the objective of this study was to determine whether major splenocyte-derived cytokines--interleukin 2 (IL-2), interleukin 4 (IL-4), interferon gamma (IFN-gamma)--and macrophage-derived cytokines--interleukin 1beta, (IL-1beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha)--were affected by ergotamine. Two sets of male BALB/c mice (n = 5/treatment) were treated with ergotamine tartrate (s.c.) for 10 d at doses of 0 (control), 0.4, 2, 10, or 50 mg/kg body weight. Twenty-four hours after the last treatment, splenocytes (S) were isolated from one set of animals and macrophages (Mphi) from the other set for determination of IL-2, IL-4, INF-gamma, and IL-1beta, IL-6, TNF-alpha, respectively. Following activation with 5 microg/ml concanavalin A (Con A) (S) and 10 microg/ml lipopolysaccharide (LPS) (Mphi), cells were incubated for 48 and 24 h, respectively, and supernatants were collected and assayed for respective cytokines by enzyme-linked immunosorbent assay (ELISA). Additionally, differential white blood cell (WBC) counts were performed and the neutrophil (N):lymphocyte (L) ratio calculated. Ergotamine treatment significantly increased IL-6 levels at the 2.0 mg/kg dose and greater and TNF-alpha at the highest dose. There was no treatment effect on IL-1beta, IL-2, IL-4, and IFN-gamma. Also, no effect was observed upon total and differential WBC counts as well as N:L ratio. Ergotamine affected the proinflammatory cytokine IL-6, and this increase may contribute to fescue tosicosis.

Ergot alkaloids (EA) such as the ergopeptine alkaloid ergotamine (ET) are adrenergic, dopaminergic, and serotonergic agents. The objective of this experiment was to investigate regional brain neurotransmitter alterations caused by EA. Male BALB/c mice were treated s.c. daily with ergotamine tartrate for 10 d at 0 (saline), 0.4, 2, 10, or 50 mg/kg body weight. Twenty-four hours after the last treatment, animals were sacrificed and brains dissected. Regional concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and metabolites 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) were measured by high-performance liquid chromatography (HPLC). Moreover, selected organ weights and plasma prolactin (PRL) were determined. Dopamine concentration was significantly reduced by ET at all doses in the striatal and hypothalamic regions. A reduction of the DA metabolite HVA occurred in striatum at only the highest dose, whereas in the hypothalamus both HVA and DOPAC were markedly reduced. Concentrations of NE, MHPG, 5-HT, and 5-HIAA were not affected by treatment in these regions. In the cerebellum, MHPG was significantly elevated at the 50 mg/kg dose. No effect of treatment was observed in the cerebrum, medulla, and midbrain. Further, no treatment-related differences in plasma PRL and organ weights other than a significant liver weight decrease at intermediate doses were found. Therefore, the effects of ET were predominantly upon DA metabolism in the corpus striatum and hypothalamus. The reductions in DA, HVA, and DOPAC indicate decreased DA synthesis.

Three sequential experiments were conducted with rabbits to 1) determine the effect of endophyte-infected (E+) tall fescue seed on rabbit performance and examine the effect of anti-ergot alkaloid immunization on rabbit performance and protectiveness against fescue toxicosis, 2) compare immunogens designed to elicit systemic anti-ergot alkaloid antibodies, and 3) select a superior adjuvant. In Exp. 1, rabbits (n = 6/treatment) fed E+ fescue seed diets (20%, 340 ppb total ergot alkaloids) had reduced (P < .05) intake and weight gain compared with endophyte-free (E-) controls, whereas apparent diet digestibility was not different between E+ and E-. Rabbits immunized against ergot alkaloids (E+ vac) with lysergol conjugated to human serum albumin (Ly-HSA) had greater (P < .05) intake than E+ rabbits during the wk 1 of a 3-wk dietary challenge. In Exp. 2, rabbits (n = 4/treatment) were immunized with Ly-HSA, with H100-B (ergot alkaloid hapten, H100-different protein carrier, B conjugate), or combinations of both with alum as adjuvant. Greatest (P < .001) anti-ergot alkaloid antibody (Ab) titer developed in the group immunized with H100-B. In Exp. 3, rabbits (n = 4/treatment) were immunized with the immunogen H100-B in conjunction with six adjuvants. Freund's incomplete adjuvant (FIA) in combination with DEAE-dextran and FIA alone gave highest anti-ergot titers. In summary, rabbit weight gain and intake were reduced by feeding E+ fescue seed diets, immunization against ergot alkaloids provided temporary improvement in intake, and H100-B conjugate with FIA or FIA + DEAE-dextran as adjuvants elicited a superior anti-ergot immune response. We believe that rabbits may serve as a model animal for fescue toxicosis research.

Ergot alkaloids cause fescue toxicosis when livestock graze endophyte-infected (E+) tall fescue. Little is known about the bioavailability of the ergot alkaloid classes (lysergic acid, lysergic acid amides, or ergopeptine alkaloids) in livestock, and this hampers development of pharmacological strategies to ameliorate the toxicosis. One method used to determine bioavailability of ergot alkaloids is to examine urinary and biliary excretion patterns. Thus, our objectives were to compare ergot alkaloid excretion via urinary or biliary systems and to determine the rate of appearance or clearance of these alkaloids in cattle that were grazing E+ or endophyte-free (E-) tall fescue. In autumn 1996, bile and urine samples were collected from eight steers (203 kg), each grazing E+ and E- tall fescue, and total alkaloid excretion was quantified using competitive ELISA. Approximately 96% of the ergot alkaloids were excreted in urine. The same steers were used to examine the rate of appearance in, or clearance from, urine when switched from E+ to E-, or from E- to E+, pastures in comparison with steers that were continuously grazing E+ or E- tall fescue at 0, 2, 5, and 7 d. Steers were returned to their original pastures after 7 d, and urine was collected at 2, 5, and 7 d. Urinary alkaloid concentrations in steers switched from E- to E+ pastures were similar (P = .55) to those in steers that continuously grazed E+ tall fescue after 2 d. Steers switched from E+ to E- pastures had urinary alkaloid concentrations similar (P = .91) to those in steers that continuously grazed E- pastures after 2 d. In 1997, two trials were conducted in which steers (191 kg) were switched or remained on E+ or E- pastures, and urine was collected at 0, 12, 24, 48, and 96 h to estimate rate of alkaloid appearance or clearance. Steers switched from E- to E+ 1) had about 33% as much urinary alkaloids as steers grazing E+ pasture after 12 h, 2) were not different after 24 h (P = .76), 3) had twice those of the E+ steers at 48 h (P < .05), and 4) were not different after 96 h. Steers switched from E+ to E- tall fescue had approximately 33% less (P < .05) urinary alkaloids than those grazing E+ at 12 h, 67% less (P < .05) at 24 and 48 h, and were not different (P = .86) from steers continuously grazing E- pastures after 96 h. Urinary alkaloid excretion patterns were similar to ergot alkaloid solubility patterns from in vitro digestion of E+ tall fescue. We suggest that alkaloids, liberated from the forage by ruminal microorganisms, were rapidly absorbed as lysergic acid amides and biotransformed ergopeptine alkaloids.

We conducted research to evaluate whether ergot alkaloids associated with endophyte-infected tall fescue could alter plasma concentrations of hormones important to reproductive function in cows. Six primiparous, estrous-cycling Holstein cows nursing calves received single i.v. injections of ergotamine tartrate, ergonovine maleate, or saline vehicle in a simple cross-over design. Each cow received one compound per estrous cycle, d 15 or 16 after estrus, and all compounds over three estrous cycles. Blood samples were collected at 20-min intervals for 40 min before and 240 min after treatments to assess plasma concentrations of prolactin, LH, FSH, and the response by PGF2alpha metabolite 13,14-dihydro-15-keto-prostaglandin F2alpha (PGFM). Ambient temperature and respiratory rates were measured hourly. Ambient temperature averaged 26 degrees C during data collection. Treatment x time was a significant source of variation for respiration rate and plasma concentrations of every hormone evaluated except FSH. Ergotamine elevated (P < .01) respiration rates 2 to 4 h after treatment. Ergotamine and ergonovine reduced (P < .001) plasma concentrations of prolactin for 2 to 4 h after treatment compared to concentrations before treatment. Plasma concentrations of LH were lowered (P < .01) by ergonovine during the 3rd h after treatment and by ergotamine during the 4th h after treatment. Most cows exhibited secretory PGFM responses after ergotamine and ergonovine treatments compared with an absence of a PGFM response in all cows after saline (P < or = .01). Results indicated that ergot alkaloids implicated as causative agents for fescue toxicosis can alter plasma concentrations of reproductive hormones during the late luteal phase of the estrous cycle in cows.

This research investigated whether ergot alkaloids associated with endophyte-infected tall fescue could alter plasma concentrations of pituitary hormones that regulate biological processes related to cattle performance. Seven Angus yearling steers received single i.v. injections of ergotamine tartrate, ergonovine maleate, or saline vehicle in a simple cross-over design. Each steer was given a different compound each week. Blood samples were collected at 15-min intervals for 45 min before and 240 min after treatments to assess plasma concentrations of prolactin, growth hormone, and LH. Respiratory rates were measured hourly to ascertain a systemic effect. Ambient temperature averaged 34 degrees C during data collection. Treatment x time was a significant source of variation for respiration rate and plasma concentrations of each hormone evaluated. Respiration rates were higher for ergonovine than for saline (P < .02) and ergotamine (P < .07) 30 min after treatment, but they were higher (P < .05) for ergotamine than for ergonovine and saline by 210 min after treatment. Both alkaloids transiently elevated (P < .01) plasma growth hormone concentrations compared with before alkaloid treatment and after saline treatment. Ergotamine reduced (P < .01) plasma concentrations of prolactin and LH throughout the 120-min period after treatment compared with concentrations before ergotamine treatment and after saline treatment. Ergonovine lowered (P < .01) prolactin concentrations for a shorter time than ergotamine and did not affect mean LH concentrations. Results indicated that ergot alkaloids implicated as contributing agents to fescue toxicosis can alter plasma concentrations of pituitary hormones important to cattle production.

Two unbred adult female goats were examined for persistent, inappropriate lactation. Prostaglandin F2 alpha treatment was ineffective in relieving the condition. Over 5 months, 1 goat developed evidence of CNS disease; this same goat had persistently high serum prolactin concentrations. At necropsy, both goats had an acidophilic adenoma of the pars distalis, a condition that, to our knowledge, has not previously been reported in goats. In addition, both goats had pheochromocytomas and cystic endometrial hyperplasia, conditions that are rarely reported in small ruminants. The inciting cause of inappropriate lactation in goats can be difficult to determine. Pituitary adenomas should be suspected when treatment with prostaglandins is unsuccessful, signs of CNS disease develop, or persistently high serum prolactin concentrations are detected.

The bioavailability of metoclopramide was investigated in three steers following administration of 8 mg/kg by the oral, abomasal (cannula), and intravenous routes, using a Latin square design. The mean (+/- SD) oral and abomasal bioavailabilities were 51.3 +/- 30.7% and 76.2 +/- 15.5%, respectively. The mean value for clearance (Cl) was 20.1 +/- 5.9 ml/min and the volume of distribution (Vd) was 0.51 +/- 0.19 l/kg. Additional pharmacokinetic parameters for metoclopramide were determined following intravenous administration to seven cows. A predominate two-compartment model of distribution was found in six cows with a t 1/2 alpha harmonic mean of 24.2 min and a range of 11.2-72.4 min, a t 1/2 beta harmonic mean of 53.1 min and a range of 31.1-134.1 min, a Cl of 42.2 +/- 8.7 ml/min, and a Vd of 2.1 +/- 0.8 l/kg. To better define the relationship between metoclopramide concentration and release of prolactin, a treatment-by-subjects infusion study was conducted in which four different loading doses followed by constant infusion were used. A steady-state metoclopramide concentration (MCPss) of 8.8 +/- 2.6 ng/ml was associated with a three-fold elevation of prolactin to a mean value of 12.1 +/- 3.1 ng/ml in six yearling steers. Steady state serum prolactin concentrations (PRLss) did not rise significantly above 23.3 +/- 6.9 ng/ml, even when MCPss reached a concentration of 518.5 +/- 151.2 ng/ml. The short half-life, moderate Vd, low minimum pharmacologically effective concentration, and rapid Cl found for metoclopramide in cattle in this study, suggest that a continuous release device could potentially be useful in the application of this drug in the prevention and treatment of fescue toxicosis.

Direct evidence linking alkaloids found in endophyte-infected tall fescue forage with the livestock disorder known as fescue toxicosis is lacking. Physiologic effects of fescue toxicosis include reduced serum prolactin concentration in cattle. A monoclonal antibody specific to the lysergic moiety of ergot alkaloids was developed in mice after creating an immunogen by linking lysergol to human serum albumin. The antibody was specific to the lysergic moiety and, therefore, it cross-reacted with ergot alkaloids, lysergic acid, and lysergol. The antibody did not cross-react with alkaloid derivatives that had bromated or hydrogenated lysergic ring moieties. Fescue toxicosis conditions were elicited in yearling Angus steers by permitting them to graze endophyte-infected tall fescue containing > 650 micrograms/kg of ergovaline for 60 days. Passive immunization of steers by infusion of the monoclonal antibody increased serum prolactin concentration by 7 ng/ml, beginning immediately after infusion. Control steers did not respond to treatment with bovine serum albumin. Active immunization of yearling Angus heifers with immunogens containing lysergol or ergonovine linked to human serum albumin resulted in an antibody response.

Plasma and pineal melatonin (MEL) and selected pineal neurochemicals (5-hydroxytryptophan, serotonin, N-acetylserotonin, dopamine, norepinephrine) associated with MEL synthesis were determined in steers grazing Acremonium coenophialum (endophyte)-infected 'Kentucky-31' tall fescue paddocks. Paddock treatments included low (LE, 33%) or high (HE, 74%) endophyte at either low (134 kg.ha-1 x yr-1, LN) or high (335 kg.ha-1 x yr-1, HN) nitrogen fertilization. Twelve pairs of yearling Angus steers were randomly assigned to three replications of the paddock treatments (LEHN, HEHN, LELN, and HELN). One steer in each of the 12 paddocks received per os either a dopamine antagonist, metoclopramide (MC; 15 mg/kg), or sucrose (S; 15 mg/kg) three times weekly for 10 wk. Blood was collected via jugular cannulas during the day and night for plasma MEL analysis and pineal glands were collected at termination. Day and night plasma MEL in the S/HEHN steers was reduced by 31.7 and 35.4% (P < .05), respectively, compared with that in S/LEHN steers. Mean night plasma MEL in the S/HELN steers was reduced by 26.7% (P < .05) compared with that in S/LELN steers. Metoclopramide reduced mean day and night plasma MEL by 22.9 and 38.3% (P < .05), respectively, in the LEHN steers and increased night MEL in the HELN animals by 35.1% (P < .05). During the day and night, there was a MC x pasture treatment interaction (P < .05). No differences were observed in either pineal MEL or the pineal neurochemicals. Acremonium coenophialum-infected fescue reduced plasma concentrations of MEL in steers, whereas treatment with MC altered plasma MEL biphasically.(ABSTRACT TRUNCATED AT 250 WORDS)

To study the effect of endophyte (Acremonium coenophialum) on hypothalamic and striatal dopamine D2 receptors, male rats (n = 14/group) were pair-fed diets containing 50% Rat Chow and 50% either endophyte-infected (E+) or noninfected (E-) fescue (Festuca arundinacea Schreb.) seed for 21 days. Concentrations of ergovaline and saturated pyrrolizidines were 1.91 micrograms/g and 2.84 mg/g, respectively in E+, and undetectable in E- fescue seed. To monitor endophyte effects, rats were weighed weekly and serum derived from trunk blood (d 21) was analyzed for prolactin. Corpus striatum and hypothalamic tissue was assayed for dopamine D2 receptors using [3H]spiperone and [125I]epidepride, respectively. The endophyte depressed (P < .06) serum prolactin concentrations. Average daily gain during the study (21 d) was depressed (P < .0043) in rats fed E+ compared to controls. The endophyte increased (P < .03) striatal D2 receptor affinity (KD = 48.70 vs 54.95 pM) with no change (P > .28) in receptor density (Bmax = 25.59 vs 28.00 pmol/mg of tissue) in E+ and E- rats, respectively. Hypothalamic D2 receptor density (Bmax = 1.79 vs 1.57 pmol/mg of tissue) and affinity (KD = 17.5 vs 17.26 pM) were not (P > .66) different between E+ and E- rats, respectively. These data suggest changes in D2 receptor binding characteristics, particularly receptor affinity, may contribute to signs of fescue toxicosis.

Two experiments were conducted to investigate the effect of feeding endophyte (Acremonium coenophialum)-infected fescue (Festuca arundinacea Shreb.) seed on LH secretion in postpartum beef cows and in cycling heifers and cows. In Exp. 1, spring-calving primiparous Angus cows (n = 16) were pair-fed for 75 d diets that contained endophyte-free or endophyte-infected (95%) fescue seed that contained 1.3 micrograms/g of ergovaline and 5.2 mg/g of saturated pyrrolizidines. Serial blood samples for basal and GnRH-stimulated serum LH analysis were obtained on d 7, 28, 42, and 56 of the study. The endophyte had no effect on LH secretion (basal, pulse frequency, and amplitude) or milk production. Average daily gain was decreased (P < .05) in cows that consumed infected fescue seed compared with controls (-.20 vs -.01 kg, respectively). Basal serum prolactin concentrations were reduced (P < .01) in treated compared with control cows (8.9 vs 25.4 ng/mL, respectively) on d 70. In Exp. 2, cycling Angus heifers (n = 8; age = 2 yr) and cows (n = 8; age = 4 yr) stratified by age were pair-fed for 40 d diets that contained the noninfected or the highly infected fescue seed. Estrus was synchronized by prostaglandin F2 alpha (d 18 and 28). Serial blood samples for serum LH analysis were obtained on d 28 (luteal phase) and d 30 (follicular phase). The endophyte did not affect LH (P > .28) or prolactin (P > .16) secretion, whereas ADG was decreased (P < .05) in treated compared with control animals (.32 vs .70 kg/d, respectively).

In an experiment with a 2x2 factorial arrangement of treatments, 32 virgin Angus heifers were used to study effects of tall fescue endophyte Acremonium coenophialum and energy supplementation on reproductive performance. Treatments were feeding of endophyte-free (EF) or endophyte-infected (EI) tall fescue without (0%) and with energy supplementation at one percent group mean body weight (1%). Blood samples were collected at 28-day intervals for prolactin (PRL). Starting 21 days before the breeding season, blood was also collected weekly for progesterone (P(4)) and PRL. After 99 days of grazing, heifers received Syncro-Mate-B (SMB) and were then artificially inseminated over a 30-day period. Heifers on EI-0% had a lower (P<0.05) average final body weight. Highest average daily gain was observed in heifers fed EF-1% (0.98 kg/day), whereas, heifers fed EI-0% had lowest average daily gain (0.53 kg/day; P<0.05). Endophyte-infected fescue depressed serum PRL concentrations (171 and 143 ng/ml vs 70 and 85 ng/ml; EF-0% and EF-1% vs EI-0% and EI-1%, respectively; P<0.05). No differences were observed among treatments in luteal activity before or after SMB, in pregnancy rates after a synchronized estrus or in overall pregnancy rates during the 30-day breeding season. Endophyte-infected fescue decreased average daily gain and depressed serum concentrations of prolactin, but had no effect on reproductive performance as measured in this study.

The response of serum luteinizing hormone (LH) to morphine, naloxone and gonadotropin-releasing hormone (GnRH) in ovariectomized, suckled (n=4) and nonsuckled (n=3) cows was investigated. Six months after ovariectomy and calf removal, the cows were challenged with 1mg, i.v. naloxone/kg body weight and 1 mg i.v. morphine/kg body weight in a crossover design; blood was collected at 15-minute intervals for 7 hours over a 3-day period. To evaluate LH secretion and pituitary responsiveness, 5 microg of GnRH were administered at Hour 6 on Day 1. On Days 2 and 3, naloxone or morphine was administered at Hour 3, followed by GnRH (5 microg/animal) at Hour 6. Mean preinjection LH concentrations (3.6 +/- 0.2 and 4.7 +/- 0.2 ng/ml), LH pulse frequency (0.6 +/- 0.1 and 0.8 +/- 0.1 pulses/hour) and LH pulse amplitude (2.9 +/- 0.5 and 2.9 +/- 0.6 ng/ml) were similar for suckled and nonsuckled cows, respectively. Morphine decreased (P < 0.01) mean serum LH concentrations (pretreatment 4.2 +/- 0.2 vs post-treatment 2.2 +/- 0.2 ng/ml) in both suckled and nonsuckled cows; however, mean serum LH concentrations remained unchanged after naloxone. Nonsuckled cows had a greater (P < 0.001) LH response to GnRH than did suckled cows (area of response curve: 1004 +/- 92 vs 434 +/- 75 arbitrary units). We suggest that opioid receptors are functionally linked to the GnRH secretory system in suckled and nonsuckled cows that had been ovariectomized for a long period of time. However, gonadotropin secretion appears not to be regulated by opioid mechanisms, and suckling inhibits pituitary responsiveness to GnRH in this model.

A ewe with apparently normal estrous cycles was unable to conceive as a result of a single ovotestis. The ovotestis was diagnosed on the basis of results from laparoscopic examination, human chorionic gonadotropin stimulation, and histologic examination of the gonad. The report reinforces the necessity of considering all causes of infertility in affected sheep, and not simply infective causes.

Fescue toxicosis in livestock is due to ingestion of endophyte (Acremonium coenophialum) -infected tall fescue. Understanding mechanisms responsible for decreased calving and growth rates, delayed onset of puberty, and impaired function of corpora lutea in heifers at puberty consuming endophyte-infected fescue is an emerging field in reproductive toxicology. The condition decreases overall productivity through a reduction in reproductive efficiency, reduced weight gains, and lowered milk production. Reproduction in cattle may be further compromised by winter coat retention, increased susceptibility to high environmental temperatures, and light intolerance. Endocrine effects in steers associated with infected tall fescue include reduced prolactin and melatonin secretions and altered neurotransmitter metabolism in the hypothalamus, the pituitary, and pineal glands. Ewes have decreased prolactin and lengthened intervals from introduction of the ram until conception. The endophyte induces prolonged gestation, thickened placentas, large, weak foals, dystocia, and agalactia in pregnant mares. Ergot peptide alkaloids, produced by the endophyte, are suggested as the primary cause of fescue toxicosis. These compounds reduce prolactin, increase body temperatures, and have powerful vasoconstrictive effects. Neurohormonal imbalances of prolactin and melatonin, with restricted blood flow to internal organs, may be the principal causes of aberrant reproduction, growth, and maturation in livestock consuming endophyte-infected tall fescue.

The effect of metoclopramide (MC), a dopamine antagonist on luteinizing hormone (LH), was examined in anestrous primaparous cows. Metoclopramide has been found to be beneficial in overcoming fescue toxicosis; increasing LH secretion stimulates return to ovulatory function after parturition. Consequently, if MC had negative effect on LH secretion, it would indicate that administration of MC to reproducing animals might be limited. Of 14 postpartum (47 to 66 days) cows, 7 were given MC (4 mg/kg of body weight, IV), and 7 served as controls. Blood was obtained via jugular cannulas at 15-minute intervals for 8 hours; MC was given at the end of the first hour, and gonadotropin-releasing hormone (GnRH, 7 mg/kg), was given IV at the end of hour 7 as a challenge stimulus for LH secretion. Prior to GnRH administration, MC did not have significant effect on LH secretion, as judged by mean serum LH concentration, LH pulse frequency, and LH pulse amplitude. Administration of MC resulted in greater (P less than 0.05) LH response to GnRH, indicating enhanced secretory ability when the pituitary gland was challenged. Serum prolactin concentration was increased (P less than 0.01) by MC administration. Therefore, MC did not have adverse effect on LH secretion in postpartum cows.

The dopamine antagonist metoclopramide monohydrochloride (MC) and the serotonin agonist quipazine maleate (Q) were administered to steers by both the oral and intravenous (i.v.) routes. Dose-response studies were designed to determine the effects of these drugs on serum prolactin (PRL) concentrations. Parameters subjected to analysis included maximal serum PRL concentrations within 1 h and the areas under the PRL response curves over time. At 1, 4, and 8 mg/kg i.v., and at 15, 30, 45, and 60 mg/kg orally, MC increased (P less than 0.05) serum PRL concentrations (difference between maximal and basal serum PRL concentrations) and increased (P less than 0.05) areas under the PRL response curves except for 1.0 mg/kg i.v. Doses of MC greater than 60 mg/kg and Q at all dosage rates were considered toxic. These studies determined a dose-response to MC in terms of serum PRL concentration and indicate that MC is well tolerated and effective for elevating serum PRL concentrations in steers. Furthermore, 4 mg/kg i.v. and 15 mg/kg orally could be considered the preferred dosage rates due to a plateau in the response above those rates.

Ultrasonography of the ovaries of 10 bitches was performed daily, using a 7.5-Mhz transducer with a built-in stand-off pad, from the onset of proestrus until the onset of metestrus. Ovarian size, shape, location, echogenicity, follicular development, and apparent ovulation were monitored. Blood samples were collected twice daily for luteinizing hormone determination and daily for progesterone determination. Vaginal smears were made daily for cytologic evaluation. Ultrasonograms were evaluated independent of hormonal and cytologic data, and the day of ovulation was noted. Initially, the ovaries were uniform and had an echogenicity that was equal to or slightly greater than that of the renal cortex. Follicles appeared as focal hypoechoic to anechoic rounded structures. Ovaries were easier to identify as follicular development progressed. Ovarian size increased with time. Apparent ovulation was characterized by a decrease in number of follicles seen from 1 day to the next, but 1 or more follicles remained in at least 1 ovary of 7 of 10 bitches. The ovaries had an oval shape that became rounded after ovulation. At some time after ovulation, all bitches had cystic (anechoic) structures indistinguishable from follicles. These structures increased in echogenicity and decreased in size with time and may have been follicles that did not ovulate, corpora hemorrhagica, fluid-filled corpora lutea, or cystic luteinized follicles. Time of ovulation determined by ultrasonography paralleled that predicted on the basis of hormonal data in 9 of 10 bitches and with cytologic findings in all bitches.

Thirty mares in late gestation were used in a 3-yr study to assess effects of the tall fescue endophyte Acremonium coenophialum on serum prolactin (PRL) and progesterone. Two paddocks of each treatment, 0 or 100% infected 'Kentucky 31' tall fescue, were grazed by the mares for 21 d. Blood was collected three times per week until parturition. At 7-d intervals, mares were challenged with thyrotropin-releasing hormone (TRH) while grazing and blood was collected postinjection. Mares grazing 100% infected tall fescue (E+) had decreased serum PRL compared with mares grazing the 0% infected tall fescue (E-) in 2 of 3 yr. Within 8 d postgrazing, serum PRL for E+ mares equaled or surpassed values of the E- mares. Serum PRL was not different during the 3rd yr. In response to TRH, serum PRL rate of increase was similar between treatments but remained elevated (P less than .01) in the E+ mares at the 180-, 240-, and 300-min sample times. Serum progesterone was lowered (P less than .05) by E+ but increased to control values within 10 d postgrazing. It is concluded that serum PRL and progesterone in the gravid mare were decreased by the presence of A. coenophialum in 'Kentucky 31' tall fescue grass but normal levels were reestablished within 2 to 3 wk.

Dopamine (DA), serotonin (5HT) and selected precursors and metabolites were measured in the anterior pituitary gland, hypothalamus and pineal gland, along with serum prolactin (PRL) and average daily gains (ADG), in steers (n = 6/group) grazing endophyte (Acremonium coenophialum)-infected and noninfected fescue (Festuca arundinacea Schreb). Paddocks (two/treatment) were designated 100F and 0F (100 and 0% infection, respectively). After 6 wk, three animals from one of the 100F paddocks were exchanged with three animals from one of the 0F paddocks, yielding 0F, 100F/0F, 0F/100F and 100F groups (n = 3). Compared to 0F steers, 100F steers had reduced serum PRL (9.23 vs 32.55 ng/ml, P less than or equal to .0001) and trial ADG (-.07 vs .28 kg, P less than or equal to .0002) but increased pituitary dihydroxyphenylacetic acid (DOPAC, a major metabolite of DA; 108 vs 59 ng/g, P less than or equal to .02) and 5-hydroxyindoleacetic acid (5HIAA, a major metabolite of 5HT; 265 vs 148 ng/g, P less than or equal to .04). Pituitary 5HIAA was greater in the steers rotated from the 0F to 100F paddocks than in steers maintained on the 0F paddocks (296 vs 148 ng/g, P less than or equal to .04). In addition pineal 5-hydroxytryptophan (5HTP, a precursor of 5HT) was increased (502 vs 280 ng/ml; P less than .08), whereas 5-methoxyindoleacetic acid (MIAA, a major metabolite of 5HIAA) and the 5HT/5HTP ratio were reduced (P less than .07) in 100F vs 0F steers. No differences among the treatment groups were observed in hypothalamic neurotransmitter and metabolite concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

These studies examined responses of serum prolactin (PRL) and growth hormone (GH) to opioid agonist and antagonist administration in heifers. To minimize nonspecific and behavioral effects and to facilitate future studies with specific opioid receptor agonists, a cannula was placed within the third cerebral ventricle of the brain of 4- to 10-mo-old heifers to directly access hypothalamic regions involved in the regulation of PRL and GH secretion. Increasing doses of morphine (M) from 2 to 1,500 micrograms injected into the third cerebral ventricle increased (P less than .001) serum PRL concentrations in a dose-related manner. Growth hormone responses were variable, resulting in elevated (P less than .05) serum concentrations following morphine, but no dose-related effects were apparent. Both PRL and GH responses to 700 micrograms M were absent when an intracerebral ventricle injection of an equimolar dose of naloxone, an opioid receptor antagonist, was administered prior to M. In a replicated 4 x 4 latin square, the effects of intravenous naloxone on PRL and GH responses was tested in young (86 +/- 11 d) and older (234 +/- 6 d) heifers. Naloxone at doses of 1, 2 and 4 mg/kg reduced (P less than .05) serum concentrations of PRL for 45 to 60 min. Mean concentrations of GH tended to be higher (P less than .07) in older heifers All doses of naloxone decreased (P less than .05) serum GH concentrations in older heifers but proved ineffective in younger heifers. There were no differences between doses of naloxone on either PRL or GH. These data suggest that endogenous opioids are involved in the regulation of PRL and GH secretion in heifers.

The response of serum luteinizing hormone (LH) to naloxone, an opiate antagonist, and gonadotropin-releasing hormone (GnRH) was measured in cows in late pregnancy to assess opioid inhibition of LH. Blood samples were collected at 15-min intervals for 7 h. In a Latin Square arrangement, each cow (n = 6) received naloxone (0, 0.5, and 1.0 mg/kg BW, i.v.; 2 cows each) at Hour 2 on 3 consecutive days (9 +/- 2 days prepartum). GnRH (7 ng/kg body weight, i.v.) was administered at Hour 5 to all cows on each day. Mean serum LH concentrations (x +/- SE) before naloxone injection were similar (0.4 +/- 0.1 ng/ml), with no serum LH pulses observed during the experiment. Mean serum LH concentrations post-naloxone were similar (0.4 +/- 0.1 ng/ml) to concentrations pre-naloxone. Mean serum LH concentrations increased (p less than 0.05) following GnRH administration (7 ng/kg) and did not differ among cows receiving different dosages of naloxone (0 mg/kg, 1.44 +/- 0.20; 0.5 mg/kg, 1.0 +/- 0.1; 1.0 mg/kg, 0.9 +/- 0.1 ng/ml). In Experiment 2, LH response to naloxone and GnRH was measured in 12 ovariectomized cows on Day 19 of estrogen and progesterone treatment (5 micrograms/kg BW estrogen: 0.2 mg/kg BW progesterone) and on Days 7 and 14 after steroid treatment. On Day 19, naloxone failed to increase serum LH concentrations (Pre: 0.4 +/- 0.1; Post: 0.4 +/- 0.1 ng/ml) after 0, 0.5, or 1.0 mg/kg BW.(ABSTRACT TRUNCATED AT 250 WORDS)

In an effort to evaluate the effect of pyoderma on circulating iodothyronines, plasma triiodothyronine (T3) and thyroxine (T4) values were determined before and after thyroid stimulating hormone administration in 25 dogs with pyoderma and in 15 controls. Basal T4 values were increased in dogs with pyoderma, but neither stimulated T4 nor T3 values were altered by this condition. On the basis of low values for circulating iodothyronines, hypothyroidism was suspected in 3 dogs in the pyoderma group. The dog with the most involved lesions had extremely low T3 and T4 values as well as an autoimmune disease. It was concluded that most dogs with pyoderma do not have thyroid dysfunction.

Cortisol and luteinizing hormone (LH) were measured in serum after the administration of adrenocorticotropic hormone (ACTH) to suckled (S) and nonsuckled (NS) beef cows. Blood was sampled on 2 consecutive days every 2 weeks for four bleeding periods starting 14 days after calving. Cows were injected with 200 IU ACTH or saline in a 2-day switchback design. Serum was collected before ACTH or saline injection and at 30-min intervals thereafter for 8 hours. Average cortisol concentrations in serum were similar in S and NS cows (6.4 +/- .6 and 6.1 +/- .8 ng/ml, respectively) after saline. Average cortisol concentrations in serum collected during an 8-hr period after ACTH on days 14, 28, 42 and 56 postpartum were 24.7 +/- 2.4, 31.8 +/- 3.5, 36.4 +/- 4.2 and 40.7 +/- .5 ng/ml, respectively, for S cows, and 31.1 +/- 2.9, 44.7 +/- 5.2, 45.0 +/- 5.7 and 46.0 +/- 5.4 ng/ml, respectively, for NS cows. Cortisol response to ACTH, measured as area under the response curve, was greater (P less than .05) in NS than in S cows. Amount of cortisol released by 200 IU ACTH was maximal by days 28 to 29 postpartum in NS cows, but the response increased gradually between days 14 to 15 and days 56 to 57 in S cows. overall, LH in serum averaged .55 +/- .08 ng/ml for S cows and .92 +/- .06 ng/ml for NS cows after saline, and .49 +/- .07 ng/ml for S cows and .94 +/- .06 ng/ml for NS cows after ACth. Although mean and peak serum LH concentrations did not differ between cows given ACTH and those given saline, the number of LH peaks and the number of cows having LH after saline. Mean serum LH concentrations were lower (P less than. 05) in S than in NS cows at 28 days postpartum. The number of LH peaks was lower (P less than .05) and the magnitude of the largest LH peak tended to be lower (P less than .06) in S cows at all sampling periods.

An experiment was designed to determine the effect of progesterone (P) or estradiol benzoate (EB) on uterine tubal transport of ova in the cow. Intramuscular injections of P, EB, or corn oil (C) were administered to heifers 24 hours after the end of estrus. The heifers were euthanatized 60 hours after the end of estrus and the location of the ovum or zygote was determined. Venous serum levels of progesterone and estradiol-17beta were measured by radioimmunoassay. The mean uterine tube (UT) length was 23.9 cm. An ovum or zygote was recovered from 11 of 14 heifers. Serum levels of progesterone and estradiol-17beta were above normal bovine levels following the P and EB treatments, respectively. The mean UT ovum transport rates were 0.42, 0.21 and 0.23 cm/hour in the P, EB and C treatment groups, respectively. The UT ovum transport rate was increased (P<0.05) by the P treatment and EB treatment had no effect (P > 0.05) when compared with the C treatment.

Adrenocortical function was assessed in dogs given a single intramuscular dose of either prednisone or triamcinolone acetonide (TCA; or saline solution to controls) to determine the duration of adrenocortical suppression caused by 2 commonly used glucocorticoids. The glucocorticoids were administered at recommended therapeutic doses; therefore, dogs given prednisone received a greater amount of glucocorticoid activity than did in dogs given TCA. Basal and ACTH-stimulated plasma cortisol concentrations, as determined by radioimmunoassay, were obtained once a week. Total intravascular eosinophil concentration and skin responses to intradermally injected histamine phosphate were quantitated. Dogs given TCA showed suppressed basal and ACTH-stimulated plasma cortisol concentrations 1 week after injection; the latter change persisted 2 weeks after injection. Adrenocortical function in 1 of 4 dogs given TCA remained suppressed for 4 weeks. In contrast, prednisone did not significantly alter adrenocortical function. Although intravascular eosinophil concentrations did not vary among groups, skin responses to intradermally injected histamine phosphate were reduced 6 days after prednisone and TCA were given.

Graded dosages of cosyntropin (synthetic corticotropin) were injected into groups of normal dogs on consecutive days. On the first day, cosyntropin was administered alone and, on the second, dogs were infused with dexamethasone three hours before cosyntropin injection. Adrenocortical function was assessed by sequential measurement of plasma cortisol (hydrocortisone) concentration. While no response differences were noted to the various amounts of cosyntropin injected with or without dexamethasone pretreatment, the magnitude of adrenocortical response was significantly greater in dogs infused with dexamethasone. It is concluded that dexamethasone pretreatment renders the canine adrenal cortex more responsive to a subsequent injection of cosyntropin. The combined dexamethasone infusion-cosyntropin injection test produces consistent adrenocortical responses in normal dogs, and has potential value in evaluation of adrenopathic dogs.

Opioid modulation of LH and prolactin (PRL) concentrations in Angus steers was investigated. In Exp. 1, morphine sulfate (M) was administered at either 1, 2 or 3 mg/kg BW (n = 4) as an i.v. injection. Blood samples were obtained at 15-min intervals for 4 h pre- and post-treatment for serum hormone analyses. Mean serum LH concentration and number of LH secretory pulses decreased (P less than .1) for 2 h after M (4.1 to nadir of 2.4 ng/ml, and .33 vs. .21 pulses/h; pre- vs post-treatment). Luteinizing hormone pulse amplitude decreased (P less than .01; 7.3 vs 2.6 ng/ml; pre- vs post-treatment) during the 2 h following M. Prolactin concentrations increased 126.6%, 170.6% and 187.6% following 1, 2 and 3 mg M/kg BW, respectively (P less than .05, 1 vs 2; P less than .01, 1 vs 3). In Exp. 2, either saline solution (S, n = 6) or M (.31 mg/kg BW, i.v. injection followed by .15 mg/(kg.h) infusion; n = 6) was given for 7 h. Concentration of LH was unaffected. Response of LH to naloxone was determined in Exp. 3. Blood samples were obtained for 2 h pre- and post-administration of either naloxone (1 mg/kg BW, i.v. injection; n = 5) or S (n = 5). Response of LH at 15, 30 and 45 min posttreatment was greater (P less than .05) in naloxone- compared with S-treated steers. In summary, M had no significant effect on serum LH concentration or LH pulse frequency, but it decreased pulse amplitude and increased serum PRL concentrations. In contrast, naloxone increased LH secretion. These observations taken together indicate a physiological role for opioid modulation of LH and PRL secretion in the steer.

Two experiments were conducted with the opioid antagonist naloxone to determine the effect of opioid receptor blockade on hormone secretion in postpartum beef cows. In Exp. 1, nine anestrous postpartum beef cows were used to measure the effect of naloxone on serum luteinizing hormone (LH), cortisol and prolactin concentrations. Cows received either saline (n = 4) or 200 mg naloxone in saline (n = 5) iv. Blood samples were collected at 15-min intervals for 2 h before and after naloxone administration. Serum LH concentrations increased (P less than .01) in naloxone-treated cows from 1.8 +/- .04 ng/ml before treatment to 3.9 +/- .7 ng/ml and 4.2 +/- .5 ng/ml at 15 and 30 min, respectively, after naloxone administration. In contrast, LH remained unchanged in saline-treated cows (1.6 +/- .3 ng/ml). Serum cortisol and prolactin concentrations were not different between groups. In Exp. 2, 12 anestrous postpartum beef cows were used to examine the influence of days postpartum on the serum LH response to naloxone. Four cows each at 14 +/- 1.2, 28 +/- .3 and 42 +/- 1.5 d postpartum received 200 mg of naloxone in saline iv. Blood samples were taken as in the previous experiment. A second dose of naloxone was administered 2 h after the first, and blood samples were collected for a further 2 h. Serum LH concentrations increased (P less than .01) only in cows at 42 d postpartum.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the effect of a glucocorticoid on thyroid and gonadal endocrine function, prednisone was administered on alternate days to dogs. The prednisone injections resulted in adrenocortical suppression, as shown by the response to ACTH. Basal plasma thyroxine and tri-iodothyronine concentrations were considerably reduced in prednisone-treated dogs. However, the thyroid response to injection of thyrotrophin-releasing hormone was not altered, indirectly demonstrating that pituitary release of TSH was not inhibited by prednisone. Similarly, the response of the thyroid to exogenous TSH was not reduced by prednisone treatment. Electron microscopic examination of thyroid tissue revealed accumulation of colloid droplets in the follicular cell cytoplasm of dogs treated with prednisone. It is postulated that prednisone may interfere with basal thyroid hormone secretion by inhibiting lysosomal hydrolysis of colloid in the thyroid follicular cell. Basal plasma concentrations of LH and testosterone, measured in the male dogs, were reduced by prednisone treatment. Responses of prednisone-treated dogs to luteinizing hormone releasing hormone were not significantly reduced. Prednisone administration did not alter testicular responsiveness to injection of human chorionic gonadotrophin. After orchidectomy, plasma LH values were significantly reduced in prednisone-treated dogs. Taken together, these results suggest that LH secretion in dogs is inhibited at the hypothalamic and/or pituitary level by prednisone administration, which consequently results in reduced testosterone concentrations.

Lambs were delivered by hysterotomy on days 142 and 143 postcoitum and were assigned to either a control group or a prednisolone-treated group (10 mg/kg daily for four days). On days 1 through 3 of life erythrocyte 2,3-diphosphoglycerate values were significantly increased in the treated group. Prednisolone treatment did not result in significantly increased P50 values. Mean plasma corticoid values in the control group decreased gradually postpartum. The prednisolone-treated lambs compared to the control lambs had depressed corticoid values, differing significantly on day 4. Body weight gains were significantly depressed by treatment and this effect lasted beyond the treatment period. On day 1 of life (24 hours postinitial treatment) oxygen consumption and cardiac output were significantly elevated in the treated group.

The effects of multiple IM injections of prednisone (2.2 mg/kg) on thyroid morphology and on plasma thyroxine (T4) and triiodothyronine (T3) concentrations in dogs were determined, and the effects of a single prednisone injection on the same circulating iodothyronine concentrations were assessed. Plasma T4 and T3 concentrations decreased significantly after 3 injections of prednisone were made. However, with a single prednisone injection, there was no significant difference in plasma T4 values between control and treated animals. Starting at 8 hours after a single prednisone injection and continuing through day 2, plasma T3 values were significantly lowered. Prednisone treatment also resulted in significantly more thyroid cytoplasmic colloid droplets per follicular cell (3.19 vs 0.57 in treated and control dogs). Lysosomal hydrolysis of colloid appeared to be inhibited by glucocorticoids in dogs, resulting in an alteration of normal thyroid gland functioning.

Morphine (M), an opioid agonist, was administered to postpartum (PP) Angus cows to investigate opioid modulation of gonadotropin secretion. In Exp. 1, eight PP cows (36.9 +/- 2.3 d) received either M (1 mg/kg; n = 4) or saline solution (S) (n = 4) via i.v. injection 36 h after calf removal. Morphine decreased (P less than .01) the number of serum LH pulses (3.0 +/- 1.1 pre- vs .3 +/- .3 post-pulses/h) and, compared with pretreatment values (3.3 mg/ml), decreased (P less than .05) mean LH at 105 min (2.1 ng/ml) through 270 min 1.9 ng/ml +/- .4). Serum prolactin (PRL) increased (P less than .01) following M from 16.4 ng/ml to a peak of 59.3 ng/ml (+/- 3.9). Serum FSH concentrations were unaffected. In Exp. 2, M (.31 mg/kg i.v. injection followed by .15 mg/(kg.h) infusion; n = 6) or S (n = 6) treatments were given for 7 h beginning 36 h after calf removal. Serum LH was similar between groups during the pretreatment and the first 6 h of infusion, but M decreased (P less than .001) the number of serum LH pulses (.44 +/- .09 vs .06 +/- .04 pulses/h). Morphine increased (P less than .05) serum PRL. It is concluded that M differentially modulated gonadotropin secretion in the cow such that PRL increased, LH decreased and FSH was unchanged.

A study was designed to examine serum concentrations of prolactin (PRL) and iodothyronines before and after thyrotropin releasing hormone (TRH) administration to agalactic (n = 26) and normally (n = 8) lactating mares. Two mg TRH was given intramuscularly (i.m.) twice daily on Day 1 (day of delivery) through Day 5. Jugular venous blood was collected on Days 1 and 5 before TRH (time 0) and at 1 and 3 h post-TRH. Basal serum concentrations of thyroxin (T(4)) were different (P < 0.05) on Day 1 (1.87 vs 1.37 mug/dl) and Day 5 (1.72 vs 1.13 mug/dl) in the normal mares and agalactic mares, respectively. There was no difference in the T(4) response to TRH. While basal serum concentrations of triiodothyronine (T(3)) were not different, agalactic mares responded with greater (P < 0.05) serum concentrations T(3) to TRH on Day 1. Following linear regression of the PRL response to TRH, slope of the lines between groups did not differ; however, elevations were significantly (P < 0.05) greater (1.79 vs 1.28 ng/ml) in control mares compared with agalactic mares, respectively, on Day 1.at 1 h post-TRH. A similar difference existed at time 0 and 1 h on Day 5. Consequently, agalactic mares had reduced basal serum T(4) values; the PRL data leads us to suggest that secretion of this hormone may be insufficient in agalactic mares.