Use of Integrative Interactomics for Improvement of Farm Animal Health and Welfare: An Example with Fescue Toxicosis.

Rapid scientific advances are increasing our understanding of the way complex biological interactions integrate to maintain homeostatic balance and how seemingly small, localized perturbations can lead to systemic effects. The 'omics movement, alongside increased throughput resulting from statistical and computational advances, has transformed our understanding of disease mechanisms and the multi-dimensional interaction between environmental stressors and host physiology through data integration into multi-dimensional analyses, i.e., integrative interactomics. This review focuses on the use of high-throughput technologies in farm animal research, including health- and toxicology-related papers. Although limited, we highlight recent animal agriculture-centered reports from the integrative multi-'omics movement. We provide an example with fescue toxicosis, an economically costly disease affecting grazing livestock, and describe how integrative interactomics can be applied to a disease with a complex pathophysiology in the pursuit of novel treatment and management approaches. We outline how 'omics techniques have been used thus far to understand fescue toxicosis pathophysiology, lay out a framework for the fescue toxicosis integrome, identify some challenges we foresee, and offer possible means for addressing these challenges. Finally, we briefly discuss how the example with fescue toxicosis could be used for other agriculturally important animal health and welfare problems.

Neurological diseases in cattle caused by plants and mycotoxins in Santa Catarina state, Brazil / Enfermidades neurológicas em bovinos causadas por plantas e micotoxinas no estado de Santa Catarina

This study described the epidemiological and clinical-pathological aspects of 25 outbreaks of neurological diseases in cattle caused by plants and mycotoxins in Santa Catarina state. Six of them were due to Sida carpinifolia poisoning, five to Solanum fastigiatum, five to Phalaris angusta, three to Claviceps paspali, three to Claviceps purpurea, and three outbreaks were of unknown etiology. The clinical signs observed in the affected cattle were mild to severe and characterized by generalized muscle tremors, incoordination, hypermetria, wide-based stance, intentional head tremors, dull staring eyes, and frequent ear twitching, with convulsions in some cases. At necropsy, lesions were observed only for P. angusta poisoning, characterized by gray-greenish discoloration in thalamus and midbrain. Microscopically, rarefaction and/or disappearance of Purkinje neurons with substitution by Bergmann cells were observed for S. carpinifolia and S. fastigiatum poisoning. For P. angusta poisoning, thin granular brown-yellowish pigment was observed in the cytoplasm of some neurons. Gross and microscopic findings were not observed in three outbreaks of tremorgenic disease of unknown etiology. Experiments conducted with leaves, flowers and seeds of Ipomoea indivisa and Ipomoea triloba, as well as with maize and soybean residues contaminated with Ipomoea spp. did not reproduced clinical signs.(AU)

Descrevem-se os aspectos epidemiológicos e clinico-patológicos de 25 surtos de enfermidade neurológica em bovinos no estado de Santa Catarina causadas por plantas e micotoxinas. Destes, seis corresponderam a intoxicação por Sida carpinifolia, cinco por Solanum fastigiatum, cinco por Phalaris angusta, três por Claviceps paspali, três por Claviceps purpurea e três surtos de etiologia não definida. Os sinais clínicos observados nos bovinos afetados eram de intensidade leve a acentuada e caracterizados por tremores musculares generalizados, incoordenação, hipermetria, aumento da base de sustentação, balanço contínuo de cabeça, olhar atento e movimentos frequentes de orelhas, e em alguns surtos convulsões. Por meio de necropsia foram observadas alterações somente na intoxicação por P. angusta as quais caracterizaram por coloração cinza-esverdeada no tálamo e mesencéfalo. Na histologia, rarefação e/ou desaparecimento de neurônios de Purkinje com substituição por células de Bergmann foram observadas na intoxicação por S. carpinifolia e S. fastigiatum. Na intoxicação por P. angusta foi observado no citoplasma de alguns neurônios do tronco encefálico com pigmentação finamente granular marrom-amarelada. Nos três surtos de enfermidade tremorgênica com etiologia não definida não foram observadas lesões macroscópicas e microscópicas. Experimentos com folhas, flores e sementes de Ipomoea indivisa e Ipomoea triloba e resíduos de milho e soja contaminados com sementes destas duas plantas não produziram alterações clínicas.(AU)

Identification of bovine prolactin in seminal fluid, and expression and localization of the prolactin receptor and prolactin-inducible protein in the testis and epididymis of bulls exposed to ergot alkaloids.

The objectives of this study were to determine (1) the presence and expression levels of bovine prolactin receptor (PRLR) and prolactin-inducible protein (PIP) in bovine testis and epididymis, and (2) the presence and concentrations of prolactin (PRL) present in seminiferous fluid in bulls consuming diets with (E+) or without (E-) ergot alkaloids. Bulls (n = 8) were sacrificed after 126 days (group A) of E+ or E- treatment or 60 days after all bulls (n = 6) were switched to the E- ration (group B). End point and real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemistry were conducted on testis and epididymis samples to establish the presence and relative expression of PRLR and PIP. Seminal fluid samples obtained from bulls consuming E- and E+ diets were subjected to RIA for PRL. Both PIP and PRLR were present in testis and epididymis as determined by reverse transcription-polymerase chain reaction and immunohistochemistry. Prolactin-inducible protein mRNA abundance was affected by time of slaughter in testis and epididymis head, respectively (P < 0.05). Prolactin receptor mRNA expression was affected by time of slaughter in the epididymis (P < 0.05) and differed in testis samples because of treatment (P < 0.05). Radioimmunoassay establishes the presence of PRL in seminal fluid; however, differences in the concentration of PRL over two separate studies were inconsistent, possibly because of differences in diet. The presence and localization of the PRLR are consistent with expression data reported for other species, and the presence of PIP and PRL in seminal fluid is consistent with data generated in humans.

Forages and pastures symposium: managing the tall fescue-fungal endophyte symbiosis for optimum forage-animal production.

Alkaloids produced by the fungal endophyte (Neotyphodium coenophialum) that infects tall fescue [Lolium arundinaceum (Schreb.) Darbysh.] are a paradox to cattle production. Although certain alkaloids impart tall fescue with tolerances to environmental stresses, such as moisture, heat, and herbivory, ergot alkaloids produced by the endophyte can induce fescue toxicosis, a malady that adversely affects animal production and physiology. Hardiness and persistence of tall fescue under limited management can be attributed to the endophyte, but the trade-off is reduced cattle production from consumption of ergot alkaloids produced by the endophyte. Improved understanding and knowledge of this endophyte-grass complex has facilitated development of technologies and management systems that can either mitigate or completely alleviate fescue toxicosis. This review discusses the research results that have led to development of 5 management approaches to either reduce the severity of fescue toxicosis or alleviate it altogether. Three approaches manipulate the endophyte-tall fescue complex to reduce or alleviate ergot alkaloids: 1) use of heavy grazing intensities, 2) replacing the toxic endophyte with nonergot alkaloid-producing endophytes, and 3) chemical suppression of seed head emergence. The remaining 2 management options do not affect ergot alkaloid concentrations in fescue tissues but are used 1) to avoid grazing of tall fescue with increased ergot alkaloid concentrations in the late spring and summer by moving cattle to warm-season grass pasture and 2) to dilute dietary alkaloids by interseeding clovers or feeding supplements.

Human and cattle ergotism since 1900: symptoms, outbreaks, and regulations.

Ergotism in humans and cattle are caused by several species of Claviceps that infect rye and other cereal grains. Symptoms in humans vary greatly and are generally classified as convulsive, gangrenous, or gastrointestinal (enteric). Cattle are particularly susceptible to both gangrenous and hyperthermic ergotism (also called summer syndrome). The prevalence of ergotism has decreased as knowledge of the fungus has increased, mainly through implementation of regulations and advances in milling procedures. However, outbreaks in humans have recently occurred in lower socioeconomic populations of Ethiopia (1977 and 2001) and India (1975) with devastating results. Prominent outbreaks in cattle have occurred in Australia (1987), the United States (1996), South Africa (1996-1997), and Brazil (1999) and, as opposed to human cases, they do not appear to be bound by economic development. This review provides a detailed summary of all major ergot epidemics since 1900 in both humans and cattle. Special attention is devoted to the ergotism symptoms and to the regulations surrounding the control of ergot in the food supply.

Efficacy of domperidone gel in an induced model of fescue toxicosis in periparturient mares.

The objective was to evaluate the efficacy of domperidone in the prevention of reproductive complications of fescue toxicosis in periparturient mares. Pregnant mares at ≤310 days of gestation were fed ≥200 µg ergovaline per kg diet daily in endophyte-infected fescue hay and seed, starting ≥30 days before their expected foaling date (EFD: 340 days after breeding). Thirty-five mares were randomized to a treatment group to receive either domperidone gel (n = 20, 1.1 mg/kg, PO, once daily) or placebo (n = 15). Treatment was initiated 10 to 15 days before the EFD and continued for 5 days after foaling. "Treatment success" was defined as foaling within 14 days of the EFD, adequate mammary development on the day of foaling, and adequate lactation for 5 days postpartum. Twenty-seven mares were included in the effectiveness analysis. More mares in the domperidone group (12/13, P < 0.0001) were treatment successes than in the control group (1/14). Gestation length was shorter (P = 0.0011), and lactation at foaling (P = 0.0011) was better for the domperidone-group mares. Foals from two control mares were born dead and four others died or were euthanized within a few days after birth, compared with one foal death (an autolyzed twin) from a domperidone-treated mare. Plasma IgG concentrations were evaluated in 24 foals. Failure of passive transfer of immunoglobulins (IgG <800 mg/dL) occurred in 13/16 (81%) foals of domperidone-group mares and 7/8 (88%) foals of control mares. In conclusion, the reproductive complications of fescue toxicosis in periparturient mares induced by a fescue seed/hay model were prevented by treatment with domperidone.

Board-invited review: St. Anthony's Fire in livestock: causes, mechanisms, and potential solutions.

After a brief history of ergot alkaloids and ergotism, this review focuses on the metabolism and mechanisms of action of the ergot alkaloids. The authors provide models of how these alkaloids afflict grazing livestock under complex animal-plant/endophyte-environmental interactions. Alkaloid chemistry is presented to orient the reader to the structure-function relationships that are known to exist. Where appropriate, the medical literature is used to aid interpretation of livestock research and to provide insight into potential modes of action and alkaloid metabolism where these are not known for livestock. In closing the paper, we discuss management of ergot alkaloid intoxication in livestock and future research needs for this field of study.

The endocrine disruptive effects of ergopeptine alkaloids on pregnant mares.

During equine gestation, ergopeptine alkaloid exposure is not uncommon, and pregnant mares are particularly sensitive to the endocrine disruptive effects of these compounds on lactogenesis and steroidogenesis. Agalactia, prolonged gestation, abortion, dystocia, and placental and fetal abnormalities are all clinical manifestations of changes in the endocrine milieu induced by the ingestion of ergopeptine alkaloid-contaminated feedstuffs by mares during late gestation. An understanding of the endocrine disruptive effects of gestational exposure to ergopeptine alkaloids is necessary for the diagnosis of potential exposures to these compounds and for effective prophylaxis and therapy.

Early harvest and ensilage of forage sorghum infected with ergot (Claviceps africana) reduces the risk of livestock poisoning.

Sorghum ergot produces dihydroergosine (DHES) and related alkaloids, which cause hyperthermia in cattle. Proportions of infected panicles (grain heads), leaves and stems were determined in two forage sorghum crops extensively infected 2 to 4 weeks prior to sampling and the panicles were assayed for DHES. Composite samples from each crop, plus a third grain variety crop, were coarsely chopped and half of each sealed in plastic buckets for 6 weeks to simulate ensilation. The worst-infected panicles contained up to 55 mg DHES/kg, but dilution reduced average concentrations of DHES in crops to approximately 1 mg/kg, a relatively safe level for cattle. Ensilation significantly (P = 0.043) reduced mean DHES concentrations from 0.85 to 0.46 mg/kg.

Growing steers grazing high versus low endophyte (Neotyphodium coenophialum)-infected tall fescue have reduced serum enzymes, increased hepatic glucogenic enzymes, and reduced liver and carcass mass.

It is well established that grazing Neotyphodium coenophialum-infected forages results in reduced BW gain and serum prolactin concentrations of cattle. The objective of this study was to determine the potential effects of toxic endophyte-infected tall fescue consumption on blood metabolites, carcass characteristics, and content of proteins critical for AA metabolism in the liver, kidney, and LM tissue of growing steers. Steers grazed a low toxic endophyte (LE; 0.023 microg/g ergot alkaloids) tall fescue-mixed grass pasture (n = 9; BW = 266 +/- 10.9 kg; 5.7 ha) or a high toxic endophyte (HE; 0.746 microg/g of ergot alkaloids) tall fescue pasture (n = 10; BW = 267 +/- 14.5 kg; 5.7 ha) from June 14 through at least September 11 (> or =89 d). No difference was observed for BW (P < 0.10) for the overall 85-d growth period. Also, no differences were observed for ribeye area/100 kg of HCW (P > 0.91), backfat (P > 0.95), or backfat/100 kg of HCW (P > 0.67). However, ADG (P < 0.01), final BW (P < 0.05), HCW (P < 0.01), dressing percentage (P < 0.01), ribeye area (P < 0.01), whole liver wet weight (P < 0.01), and whole liver wet weight/100 kg of end BW (P < 0.01) were greater for LE steers than HE steers. After 85 d of grazing, serum concentrations of alkaline phosphatase (P < 0.05), alanine aminotransferase (P < 0.01), aspartate aminotransferase (P < 0.03), cholesterol (P < 0.01), lactate dehydrogenase (P < 0.01), and prolactin (P < 0.01) were less for HE than LE steers. At slaughter, hepatic content of cytosolic phosphoenolpyruvate carboxykinase (P < 0.01) was greater in HE steers than LE steers. Hepatic content of aspartate aminotransferase (P < 0.01) also was greater, whereas renal and LM content were not (P > or = 0.42). No differences (P > or = 0.15) were observed for hepatic, renal, and LM content of alanine aminotransferase, glutamate dehydrogenase, glutamine synthetase, and 3 glutamate transport proteins. These data indicate that the HE steers displayed classic endophyte toxicity symptoms for growth and blood variables, classic symptoms that were concomitant with novelly identified altered glucogenic capacity of the liver and decreases in carcass characteristics.

Effect of feeding sorghum ergot (Claviceps africana) to sows during mid-lactation on plasma prolactin and litter performance.

Diets containing 3% sorghum ergot (16 mg alkaloids/kg, including 14 mg dihydroergosine/kg) were fed to 12 sows from 14 days post-farrowing until weaning 14 days later, and their performance was compared with that of 10 control sows. Ergot-fed sows displayed a smaller weight loss during lactation of 24 kg/head vs. 29 kg/head in control sows (p > 0.05) despite feed consumption being less (61 kg/head total feed intake vs. 73 kg/head by control sows; p < 0.05). Ergot-fed sows had poorer weight gain of litters over the 14-day period (16.6 kg/litter vs. 28.3 kg/litter for controls; p < 0.05) despite an increase in consumption of creep feed by the piglets from the ergot-fed sows (1.9 kg/litter compared with 1.1 kg/litter by the control; p > 0.05). Sow plasma prolactin was reduced with ergot feeding after 7 days to 4.8 microg/l compared with 15.1 microg/l in the control sows (p < 0.01) and then at weaning was 4.9 microg/l compared with 8.0 microg/l (p < 0.01) in the control sows. Two sows fed ergot ceased lactation early, and the above sow feed intakes, body weight losses with litter weight gains and creep consumption indirectly indicate an ergot effect on milk production.

Feeding sorghum ergot (Claviceps africana) to sows before farrowing inhibits milk production.

OBJECTIVE: To assess the impact of feeding different amounts of sorghum ergot to sows before farrowing. DESIGN: Fifty-one pregnant sows from a continually farrowing piggery were sequentially inducted into the experiment each week in groups of four to seven, as they approached within 14 days of farrowing. Diets containing sorghum ergot sclerotia within the range of 0 (control) up to 1.5% w/w (1.5% ergot provided 7 mg alkaloids/kg, including 6 mg dihydroergosine/kg) were randomly allocated and individually fed to sows. Ergot concentrations were varied with each subsequent group until an acceptable level of tolerance was achieved. Diets with ergot were replaced with control diets after farrowing. Post-farrowing milk production was assessed by direct palpation and observation of udders, and by piglet responses and growth. Blood samples were taken from sows on three days each week, for prolactin estimation. RESULTS: Three sows fed 1.5% ergot for 6 to 10 days preceding farrowing produced no milk, and 87% of their piglets died despite supplementary feeding of natural and artificial colostrums, milk replacer, and attempts to foster them onto normally lactating sows. Ergot inclusions of 0.6% to 1.2% caused lesser problems in milk release and neo-natal piglet mortality. Of 23 sows fed either 0.3% or 0.6% ergot, lactation of only two first-litter sows were affected. Ergot caused pronounced reductions in blood prolactin, and first-litter sows had lower plasma prolactin than multiparous sows, increasing their susceptibility to ergot. CONCLUSION: Sorghum ergot should not exceed 0.3% (1 mg alkaloid/kg) in diets of multiparous sows fed before farrowing, and should be limited to 0.1% for primiparous sows, or avoided completely.

Presumptive gangrenous ergotism in free-living moose and a roe deer.

Presumptive gangrenous ergotism in 10 moose (Alces alces) and one roe deer (Capreolus capreolus) is reported. Three of the moose came from a municipality in southeastern Norway where the disease occurred as a cluster in 1996. The other moose represented solitary or sporadic cases diagnosed in four municipalities in northwestern Norway between 1996 and 2004. Affected moose (seven calves, three yearlings) were found between October and June, showing distal limb lesions on one to three limbs. The lesions in the moose found during October and November presented as dry gangrene, whereas moose found between December and June presented with loss of the distal part of the limbs or open lesions close to sloughing. Four of the moose also had bilateral ear lesions affecting the outer third of the pinnae. A retrospective diagnosis of ergotism (June 1981) was made in a 1-yr-old roe deer from northwestern Norway showing loss of the distal part of all four limbs.

Claviceps cyperi, a new cause of severe ergotism in dairy cattle consuming maize silage and teff hay contaminated with ergotised Cyperus esculentus (nut sedge) on the Highveld of South Africa.

During December/January 1996/97 typical summer syndrome (hyperthermia and a 30% drop in milk yield) occurred in succession in two Holstein dairy herds (n=240 and n=150 milking cows, respectively) on the South African Highveld. These farms are situated in the midst of the prime maize and dairy farming areas of South Africa where this condition had never been diagnosed before. The individual components of the concentrate on both farms were negative for ergot alkaloids. Endophytic fungi and/or ergot infestation of teff and other grasses fed to the cows were then suspected of being involved, but neither endophytes nor ergot alkaloids could be implicated from these sources. By measuring the serum prolactin levels of groups of sheep (n=5) fed the first farm's total mixed ration (TMR) or its three individual fibre components for a period of 11 days, the source of the ergot alkaloids was identified. A statistically significant decrease in the level of this hormone occurred only in the group on maize silage (which constituted 28% on dry matter base of the TMR). The involvement of the maize silage was further chemically confirmed by the high levels of total ergot alkaloids, predominantly ergocryptine, found by LC-MS in the silage as well as in the TMR (115-975 ppb and 65-300 ppb, respectively). The ergot alkaloid content (mainly ergocryptine) of the maize silage on the second affected farm was 875 ppb. Withdrawal of contaminated silage resulted in gradual recovery of stock on both farms. Nut sedge (Cyperus esculentus and Cyperus rotundus of the family Cyperaceae) has a world-wide distribution and is a common weed in annual crops, and can be parasitized by Claviceps cyperi. Careful examination of the maize silage from both farms revealed that it was heavily contaminated with nut sedge and that it contained minute sclerotia, identified as those of Claviceps cyperi, originating from the latter. Nut sedge was abundant on both farms and it is believed that late seasonal rain had resulted in mature, heavily ergotised nut sedge being cut with the silage. Claviceps cyperi sclerotia, collected on the affected fields in the following autumn contained 3600-4000 ppm ergocryptine. That the dominant alkaloid produced by this particular fungus was indeed ergocryptine, was confirmed by negative ion chemical ionization MS/MS. In one further outbreak in another Holstein herd, teff hay contaminated with ergotised nut sedge and containing 1200 ppb alkaloids, was incriminated as the cause of the condition. This is the first report of bovine ergotism not associated with the Poaceae infected with Claviceps purpureum or endophytes but with the family Cyperaceae and this particular fungal phytopathogen.

Gangrenous ergotism in cattle grazing fescue (Festuca elatior L.) in South Africa.

The 1st outbreak of fescue toxicosis in South Africa was recently confirmed in a Brahman herd at Perdekop, near Standerton, in Mpumalanga province, South Africa. Within 3 weeks of being placed on a fescue pasture in mid-winter, 50 of 385 cattle developed lameness and/or necrosis of the tail. The farmer had established Festuca elatior L. (tall fescue, Iewag variety) on c. 140 ha for winter grazing. Fescue may be infected by an endophyte, Neotyphodium coenophialum, which produces ergot alkaloids, in particular ergovaline. Ergovaline concentrations in basal leaf sheaths and grass stems collected during the outbreak ranged from 1720-8170 ppb on a dry-matter basis.

Thermoregulatory response of dairy cows fed ergotized barley during summer heat stress.

Claviceps purpurea infects the seed heads of cereal grains and grasses and produces ergopeptine alkaloids that cause hyperthermia and agalactia in cattle during periods of heat stress. A field experiment was undertaken to examine the effects of ergopeptine alkaloids found in barley on thermal status of dairy cattle during periods of heat stress. Production end points were also measured to identify the effect of the change in thermal status. Contaminated barley screenings containing known levels of ergopeptine alkaloids were fed to lactating Holstein cattle (10 microg total ergopeptine alkaloids/kg BW/day) for 10 days during summer heat stress. Air temperature increased 14.4 C during the first 8 days of treatment and then declined the same during the last 2 days. Extreme daily values for rectal temperature and respiration rate, using averages of all animals, showed maximum increases of 2.3 C and 56.8 breaths/minute, respectively, during this period. Group afternoon milk production decreased 2 kg/day during the heat stress period, with no measurable change in feed intake. A greater level of hyperthermia occurred in cattle consuming the diet with ergopeptine alkaloids, with only marginal symptoms of ergot toxicosis reflected in feed intake and milk production. Therefore, the ergopeptine alkaloid dose used in this study represents a level for minimal induction of the ergot toxicity response.

Hyperthermic syndrome in dairy cattle associated with consumption of ergots of Claviceps purpurea in southern Brazil.

A hyperthermic syndrome (HS) associated with consumption of ration contaminated with Claviceps purpurea is described in 4 dairy cattle herds from different counties in the state of Rio Grande do Sul, southern Brazil. Outbreaks of this mycotoxicosis occurred during the summer of 1999-2000 and autumn of 2002 when 25% to 70% of cattle from those herds were affected. The disease occurred after the introduction of a new batch of feed contaminated with sclerotia of C. purpurea. First clinical signs were observed up to 3 mo after the ration was introduced and consisted of pyrexia, intense salivation and drooling, open-mouth, difficult breathing, in some cases with the tongue protruded, decrease in milk yield, decrease in food intake and weight loss. Affected cattle compulsively sought shade or water ponds. Signs were more pronounced during daytime. The severity of the clinical picture varied according to changes in environmental temperature during the day. There was complete recovery approximately 60 d after feeding with the contaminated ration was discontinued. Abortions occurred during the outbreak and soon after the remission of the clinical signs associated with HS. In one of the herds, reproductive performance and fertility were seriously impaired even after clinical signs of HS completely disappeared. Diagnosis was based on epidemiology, clinical signs and pathology. The pathogenetic mechanisms involved in the occurrence of HS are briefly discussed.

Use of nonergot alkaloid-producing endophytes for alleviating tall fescue toxicosis in sheep.

Nonergot alkaloid-producing endophytes from New Zealand were inserted into tall fescue (Festuca arundinacea) cultivars in an attempt to address the problem of fescue toxicosis in grazing sheep. A 3-yr grazing study was conducted to determine lamb performance and to evaluate toxicosis in lambs grazing nonergot alkaloid-producing endophyte-infected (AR542 or AR502), endophyte-free (E-), or wild-type toxic endophyte-infected (E+) Jesup tall fescue or nonergot alkaloid-producing endophyte-infected (AR542) Georgia-5 tall fescue. Replicated 0.11-ha tall fescue paddocks were established at the central Georgia Branch Station during September 1997 and stocked with lambs from spring 1998 through autumn 2000. Mean ergot alkaloid concentrations were higher (P < 0.01) in E+ forage than in AR542, AR502, and E- tall fescue, and ergot alkaloid concentrations in E- plants and plants infected with AR542 and AR502 were low. Forage availability did not differ (P = 0.92) across treatments during autumn and was higher (P < 0.05) in Georgia-5 AR542 than in Jesup AR502 and E+ pastures. Initial serum prolactin (PRL) concentrations did not differ (P = 0.58) across treatments during autumn, but were higher on Jesup AR542 than E+ during spring. Post-treatment serum PRL concentrations were depressed (P < 0.01) on E+ compared with AR542, AR502, and E- in both spring and autumn. Signs of heat stress were observed in E+ lambs during periods of high ambient temperatures. Mean post-treatment rectal temperature and mean stocking rate exhibited treatment x year interactions (P < 0.05). Lamb ADG was higher (P < 0.05) on AR542, AR502, and E- than on E+ tall fescue. Similarly, gain/hectare was higher (P < 0.015) on AR542, AR502, and E- than on E+. Tall fescue pastures containing AR542 and AR502 endophytes yielded lamb performance that did not differ from that on E- tall fescue and which was superior to performance on E+ tall fescue. Depressed PRL concentrations and elevated rectal temperatures as indicators of toxicosis were evident only in lambs grazing E+ tall fescue, suggesting that nonergot alkaloid-producing endophyte-infected tall fescue is a viable alternative for alleviating tall fescue toxicosis.