Enhanced resistance to listeriosis induced in mice by preinoculation treatment with T-2 mycotoxin

The effect of T-2 toxin on cell-mediated resistance to bacterial infection was evaluated in mice challenge exposed with Listeria monocytogenes. Mice were treated orally on days -5, -4, -3, -2, -1, +1, and +3 with 2.0, 1.0, 0.5, or 0 mg of T-2 toxin/kg of body weight and were exposed to 10(6) (LD100) or 10(5) (LD50) L monocytogenes by intraperitoneal injection on day 0. Necrosis and depletion of lymphocytes in the thymus and spleen, decrease in thymus weight, reductions in the number of circulating total leukocytes and lymphocytes, and necrotizing gastroenteritis occurred in the toxin-treated mice. Although the cytotoxic effect of T-2 toxin on lymphoid tissue was marked, enhanced resistance to Listeria infection was revealed by significant (P less than 0.01) decreases in mortality caused by listeriosis in the toxin-treated mice. Mortality decreased from 100% to 64% in the mice exposed to 10(6) Listeria and from 50% to 20% in the mice exposed to 10(5) Listeria. Percentage of mortality after Listeria challenge exposure was dependent on the T-2 toxin dose and was progressively decreased in the mice given 0.5, 1.0, or 2.0 mg of toxin/kg.     

Comparison of the effect of T-2 toxin with that of dexamethasone or cyclophosphamide on resistance to Babesia microti infection in mice

The effect of T-2 toxin on host resistance to acute and latent Babesia microti infections was evaluated in mice and was compared with the effects of the immunosuppressive drugs dexamethasone and cyclophosphamide. Mice with acute or latent B microti infection were treated with 2 mg of T-2 toxin/kg of body weight, 0.2 mg of dexamethasone/kg, or 30 mg of cyclophosphamide/kg daily for 5 days. Treatment with dexamethasone or cyclophosphamide caused significant (P less than 0.05) increases in Babesia parasitemia during acute infection and significantly (P less than 0.05) prolonged the duration of parasitemia during acute babesiosis. Treatment with T-2 toxin caused a transient significant (P less than 0.05) increase in Babesia parasitemia on day 10 after acute infection and numerical, though statistically nonsignificant, increases in the maximal level and duration of parasitemia during acute babesiosis. Significant (P less than 0.005) recrudescence of parasitemia was observed in the dexamethasone- and cyclophosphamide-treated mice with latent Babesia infection. Treatment with T-2 toxin did not cause recrudescence of parasitemia in mice with latent Babesia infection.     

Immunotoxic effects of T-2 mycotoxin on cell-mediated resistance to Listeria monocytogenes infection

The effect of T-2 toxin on cell-mediated resistance to bacterial infection was evaluated in mice exposed to Listeria monocytogenes. Mice were inoculated with 4.0 X 10(5) (LD50) or 4.0 X 10(4) (nonlethal) L. monocytogenes on day 0 and treated orally on days 0, 1, 2, and 3 with 2.0, 1.0, or 0 mg/kg T-2 toxin. Toxin induced suppression of resistance was indicated by the rapid growth of Listeria in the spleen and by significant (P less than 0.005) increases in mortality due to listeriosis. Necrosis and depletion of lymphoid tissue, lymphopenia, and a marked decrease in the influx of lymphocytes and macrophages into Listeria elicited peritoneal exudates and at sites of infection in the liver and spleen occurred in the toxin treated mice. The immunotoxic effect of T-2 toxin on cell-mediated resistance to listeriosis was dosage dependent and attributed to toxin induced lymphoid depletion and the failure of surviving lymphocytes and mononuclear cells to clear the host of infection.     

The effects of dietary T-2 toxin on acute herpes simplex virus type 1 infection in mice

Young male white Swiss mice were fed control diet or diet supplemented with 20 or 10 parts per million (ppm) of T-2 toxin for two or three weeks. These mice then were inoculated with herpes simplex virus type 1 (HSV-1) (9.6 x 10(6) plaque forming units) intraperitoneally. To compare the effects of T-2 toxin against a known immunosuppressive drug, cyclophosphamide was injected intraperitoneally at 150 mg/kg, 24 hours after treatment with HSV-1, into mice fed the control diet. Mice were necropsied and tissues were collected for microscopic and virologic examination. White Swiss mice which consumed a daily diet containing 20 ppm of T-2 toxin for two or three weeks were highly susceptible to HSV-1 infection and 27 of 36 (75%) died as a result of extensive hepatic and adrenal necrosis. Although HSV-1 was isolated from livers and brains of mice fed 20 ppm of T-2 toxin for two or three weeks, there was little or no inflammatory response found in the adrenals, livers, spinal cords, brains, or ganglia. The necrotizing encephalomyelitis observed in control mice was absent. High levels of dietary T-2 toxin appeared to be more immunosuppressive than cyclophosphamide because only one mouse died after treatment with HSV-1 and cyclophosphamide. Mice treated with cyclophosphamide had changes in brain, spinal cord, spleens, thymus, and bone marrow which were similar to those fed 20 ppm of T-2 toxin and infected with HSV-1, however, liver lesions were much less severe. HSV-1-infected mice on a diet with 10 ppm T-2 toxin had lesions of intermediate severity when compared with HSV-1-infected mice fed a diet with 20 ppm T-2 toxin and HSV-1-infected mice on control diets. Necrosis was less extensive in the livers and adrenals. The infrequent isolation of virus from liver and brain was consistent with the lack of intranuclear inclusion bodies and a more marked inflammatory response. Ten ppm of dietary T-2 toxin only depressed bone marrow and splenic red pulp to a mild or moderate degree. This may have enhanced the necrotizing encephalomyelitis observed in mice killed on days 6 and 8 after HSV-1 infection. Liver lesions were mild and those of the adrenals were moderate in mice fed control diet. The rare isolation of HSV-1 from the liver and brain and the findings of a moderate to severe necrotizing encephalomyelitis in these mice was consistent with an essentially functional immune system.     

Regulation of murine macrophage phagocytosis of sheep erythrocytes by T-2 toxin

The effect of a single oral dose of 4 mg of T-2 toxin/kg of body weight on in vivo phagocytosis of sheep RBC by peritoneal macrophages was evaluated in nonsensitized mice and in mice sensitized with sheep RBC. T-2 toxin treatment had no effect on the viability or phagocytic activity of resident peritoneal macrophages in nonsensitized mice. However, a significant (P less than 0.005) increase in phagocytic activity occurred in cells from mice treated with toxin and subsequently sensitized with sheep RBC. In contrast, phagocytosis of sheep RBC was significantly (P less than 0.05) suppressed in cells from mice treated with toxin after sensitization. Toxin treatment induced necrosis of lymphocytes and significant decreases in thymus and spleen weights. Seemingly, T-2 toxin, administered at a dose that caused marked lymphoid depletion, suppressed or enhanced in vivo macrophage phagocytic activity in antigenically sensitized mice, and enhancement or suppression of phagocytosis was a function of the time of toxin treatment in relation to antigenic stimulation.     

Characterization of the toxicity of the mycotoxins aflatoxin, ochratoxin, and T-2 toxin in game birds. III. Bobwhite and Japanese quail.

Bobwhite and Japanese quail were fed diets containing 1.25, 2.50, or 5.00 ppm aflatoxin; 1, 2, or 4 ppm ochratoxin A (OA); or 4, 8, or 16 ppm T-2 toxin. Aflatoxin induced mortality in bobwhites during the second and third week with 1.25 ppm (10%), 2.50 ppm (30%), and 5.00 ppm (40%), and during the same period with T-2 toxin at 8 ppm (20%) and 16 ppm (22.5%). Body weights of bobwhite quail were significantly decreased by the two higher levels of aflatoxin by 2 weeks of age, and by the two higher levels of T-2 toxin by 1 week of age. In Japanese quail, only the highest level of aflatoxin and T-2 toxin reduced body weight (by 3 weeks and by 1 week of age, respectively), and even then to a much lesser extent than in bobwhites (less than 10%). Aflatoxin did not affect feed-conversion ratio (FCR) in bobwhite quail, but the two higher levels of T-2 toxin increased FCR. None of the toxins induced mortality or increased the FCR in Japanese quail. Aflatoxin increased liver weight in both bobwhite and Japanese quail. OA increased kidney weight in 3-week-old Japanese quail but had no effect on the kidney weight of bobwhite quail. Mouth lesions were progressively more severe in bobwhite quail fed increasing levels of T-2 toxin, but lesions were far less severe in Japanese quail.     

Subacute toxicity of Dietary T-2 toxin in mice: influence of protein nutrition.

The subacute toxic effects of dietary T-2 toxin (20 ppm) incorporated in semipurified diets of 8%, 12% or 16% protein, were examined in young Swiss mice after one, two, three and four weeks. Dietary T-2 toxin caused substantial reductions in growth and food consumptaion, the degrees of which were greatest in mice fed the diets of reduced protein content. T-2 toxin consistently caused similar degrees of nonregenerative anemia, lymphopenia, thymic atrophy and gastric hyperkeratosis irrespective of the dietary protein level. However, erythroid hypoplasia was temporary in mice fed T-2 toxin in the 16%-protein diet such that erythroid precursors regenerated in splenic and bone marrow and were hyperplastic after four weeks. Liver to body weight ratios of mice fed T-2 toxin in the 16%-and 12%-protein diets increased during the four week trial in comparison to control mice fed at a similar rate. These observations indicated that suppression of erythropoiesis in mice by dietary T-2 toxin was temporarty and that the interval before regeneration was prolonged by diets of reduced protein content.     

Mast cell tumor destruction by deionized water

In a controlled study, malignant murine P815 mastocytoma cells exposed in vitro to distilled and deionized water died as a result of progressive swelling, degranulation, and membrane rupture. A 90% mean cell death occurred when cells obtained directly from culture were exposed to deionized water for 2 minutes. Of 6 cryopreserved malignant murine cell lines, which included Cloudman S91 melanoma, CMT-93 rectum carcinoma, MMT-06052 mammary carcinoma, and S-180 Sarcoma, only P815 mastocytoma and YAC-1 lymphoma were significantly (P less than 0.05) affected by hypotonic shock; Cloudman S91 melanoma cells were the most resistant. Mastocytoma cells were selectively killed by hypotonic solution, and lymphoma cells were also killed by isotonic saline solution. Local mast cell tumor (MCT) recurrence and percentage survival were evaluated in 12 cats (21 MCT) and 54 dogs (85 MCT) subjected to surgery alone or local infiltration of deionized water as an adjunct to surgery. Of all 16 incompletely excised MCT in cats, there was no local recurrence following injection. Four mast cell tumors (2 cats) regressed after being injected in situ. In dogs with clinical stage-I MCT, local recurrence was detected in 50% (5/10), but with injection after incomplete excision, local MCT recurrence was significantly (P less than 0.05) less (6.6%, 1/15). Percentage recurrence was significantly (P less than 0.05) less and survival significantly greater when incompletely excised grade-II MCT were injected. Mean follow-up period after surgery in cats and dogs was 35 and 23.4 months, respectively.     

Characterization of the toxicity of the mycotoxins aflatoxin, ochratoxin, and T-2 toxin in game birds. II. Ringneck pheasant.

Ringneck pheasants were fed diets containing 1.25, 2.5, or 5 ppm aflatoxin; 1, 2, or 4 ppm ochratoxin A (OA); or 4, 8, or 16 ppm T-2 toxin. Severe toxin-induced mortality was seen during the first to third weeks with 2.50 and 5.00 ppm aflatoxin (92.5% and 97.5%, respectively), compared with the mortality in control pheasants fed no toxin (0%). Slight mortality (less than or equal to 5%) was seen with OA and T-2 toxin. Body weights were significantly decreased by the lowest level (1.25 ppm) of aflatoxin by 2 weeks of age, by the two highest levels of aflatoxin by 1 week of age, and by 16 ppm T-2 toxin by 1 week of age. The feed-conversion ratio was increased by 2.50 and 5.00 ppm aflatoxin compared with the feed-conversion ratio in controls, although high mortality may have influenced the results. Aflatoxin had no effect on liver weight, but OA increased kidney weight in 3-week-old pheasants. Mouth lesions were seen in some of the pheasants fed T-2 toxin.     

Anti-tumor evaluation of benzaldehyde in the dog and cat

Fourteen dogs and 11 cats with various malignant tumors were treated daily with benzaldehyde at a dosage rate of 10 mg/kg of body weight, orally, divided into 4 doses. Clinical signs of toxicosis were not observed. A partial response (greater than 50% regression) was observed in animals with an oral squamous cell carcinoma and an oral melanoma. A minimal response (less than 50% regression) was observed in animals with a sweat gland adenocarcinoma and a mast cell sarcoma. One dog with an oral melanoma had stabilization of tumor growth for 8 weeks. Seemingly, benzaldehyde has only minimal anti-tumor activity at the dose studied.     

Embryotoxic effects of prenatal T-2 toxin exposure in mice.

Pregnant CD-1 mice were administered T-2 toxin by gastric intubation on day 11 of gestation at dosages of 0, 0.75 and 1.5 mg/kg. The T-lymphocyte dependent antibody response against sheep red blood cells which was evaluated in the offspring at six weeks of age was not affected by T-2 toxin exposure. Individual birth and weaning weights were not influenced by T-2 toxin, but the litter size was reduced in the high dose group, without affecting the number of implantation sites per dam. The number of female offspring produced by dams exposed to 1.5 mg/kg T-2 toxin was less compared to other treatment groups, suggesting that the female fetus was more susceptible to embryolethal effects of prenatal T-2 toxin exposure. These results suggest that prenatal T-2 toxin exposure is unlikely to be a significant health problem with respect to primary humoral immunity. At the dosages given, T-2 toxin produced substantial embryotoxicity without alteration in antibody production. The embryolethal effects are a primary limiting factor which may preclude the expression of any immunoteratological manifestations associated with humoral immunity under natural field conditions.     

Characterization of the toxicity of the mycotoxins aflatoxin, ochratoxin, and T-2 toxin in game birds. I. Chukar partridge

Chukar partridges were fed diets containing 1.25, 2.5, or 5 ppm aflatoxin; 1, 2, or 4 ppm ochratoxin A (OA); or 4, 8, or 16 ppm T-2 toxin. Toxin-induced mortality was seen during the third week with 4 ppm OA (12.5%) and 16 ppm T-2 toxin (15%), compared with the mortality in control chukars fed no toxin (2.5%). Body weights were significantly decreased by the highest level of aflatoxin at 3 weeks of age, by the highest level of OA by 2 weeks of age, and by 8 and 16 ppm T-2 toxin by 1 week of age. Aflatoxin did not affect liver weight and OA did not increase kidney weight in 3-week-old chukars. There was a slight decrease in kidney weight in chukars fed 4 ppm OA; however, the decrease was related to the decrease in body weight produced by the toxin. Mouth lesions were seen at all levels of T-2 toxin fed.     

Hormonal changes in sows after induced porcine parvovirus infection in early pregnancy

Hormonal changes, lesions, and virus isolation studies were determined in sows after uterine artery inoculation with porcine parvovirus [( PPV], strain NADL-8) in early pregnancy. Two sows were given PPV on days 14 or 16 and were euthanatized and necropsied on day 35 after twice daily plasma collection for hormone measurement. Parvovirus was given to 4 sows on day 14 and to 4 sows on day 21 with 5 times daily plasma samples collected for 1 week. Sows were examined on days 21 and 28, respectively. Four control sows in each group on days 14 and 21 were given a placebo injection and were similarly studied. All embryos in all but 1 sow given PPV were in various stages of resorption at necropsy. Normal embryos were present in all control sows. Estrone sulfate values increased logarithmically, progesterone values remained stable, and concentrations of 13, 14-dihydro-15-keto-prostaglandin (PG) F2 alpha (PGFM), a PGF2 alpha metabolite, were less than 200 ng/ml for sows given a placebo. In contrast, sows with resorbing embryos did not have an increase in estrone sulfate values. A decrease in plasma progesterone values occurred in 9 of 10 sows inoculated with PPV; this decrease was accompanied by greater than or equal to 1 marked increase in PGFM concentrations. Quantitative assessment of the uterus revealed significantly greater cytoplasmic density in endometrial and glandular cell (P less than 0.01), a greater glandular epithelium height (P less than 0.05), and twice the number of glands (P less than 0.05) in control sows, compared with values in sows inoculated with PPV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathologic, hematologic, and serologic changes in rabbits given T-2 mycotoxin orally and exposed to aerosols of Aspergillus fumigatus conidia

The influence of immunosuppression by T-2 mycotoxin on the fungal disease aspergillosis was investigated in rabbits. Four groups of rabbits (groups 1A, 1B, 3A, and 3B) were given 0.5 mg of T-2 toxin/kg of body weight/day, PO; in addition, rabbits of groups 3A and 3B were exposed to aerosols of Aspergillus fumigatus conidia from days 7 through 16. Rabbits of groups 2A and 2B were exposed to A fumigatus aerosols, but were not given T-2 toxin, and rabbits of group 0 served as controls. Two rabbits of group 1A, 1 rabbit of group 1B, and 1 rabbit of group 3A died before scheduled necropsy. Rabbits of groups 1A, 2A, and 3A were killed and necropsied on day 17, and the remaining rabbits (groups 0, 1B, 2B, and 3B) were killed and necropsied on day 28. Changes caused by T-2 toxin included leukopenia, marginal anemia, and increased number of and morphologic changes in nucleated erythrocytes by day 21, followed by a regenerative hematologic response. Serum alkaline phosphatase and sorbitol dehydrogenase activities and antibody response to A fumigatus (as measured by an indirect hemagglutination test) were decreased by T-2 toxin ingestion. Rabbits with aspergillosis had leukocytosis, increased PCV, and increased antibody response to A fumigatus. Histologic lesions consisting of centrilobular hepatocellular swelling, portal and periportal fibrosis, and lymphocyte necrosis and/or depletion within secondary lymphoid tissue were observed in most rabbits treated with T-2 toxin. Normal defense mechanisms against A fumigatus infection were compromised by T-2 treatment, as evidenced by the severity and extent of lung lesions, greater number of hyphal elements observed, and greater number of colonies of A fumigatus isolated from rabbits of groups 3A and 3B. There were no significant changes in group-0 rabbits.     

Effect of T-2 toxin on resistance to systemic Salmonella typhimurium infection of newly hatched chickens

Newly hatched chickens were treated with the trichothecene mycotoxin, T-2 toxin, during the first day of life. Control chickens were treated with other agents known to cause immunosuppression--cyclosporine, cyclophosphamide, and aflatoxin. Chickens were infected on day 6 (5 days after treatment with T-2 toxin) by intraperitoneal inoculation with Salmonella typhimurium. Blood samples were collected from treated chickens (noninfected) and used to assess the responsiveness of blood lymphocytes to T-cell or B-cell mitogens, phytohemagglutinin, or lipopolysaccharide, respectively. The T-2 toxin had a profound negative effect on the ability of the chickens to resist salmonellosis, as measured by survival. However, the toxin effect in reducing phytohemagglutinin- and lipopolysaccharide-stimulated mitogenesis, though significant (P greater than 0.05), was not severe. Our data indicate a direct effect of T-2 toxin on native resistance to systemic salmonellosis, which was not accompanied by marked alteration in T- or B-cell responses to mitogenic stimulation.     

Experimental inoculation of day-old ducks with Brachyspira pilosicoli and B. alvinipulli

Two groups of one-day-old Peking ducklings (Groups I and II, 12 birds/group) were inoculated orally with Brachyspira pilosicoli and two groups with B. alvinipulli (Groups III and IV, 12 birds/group). T-2 toxin was added to the feed of Groups II and IV in a dose of 1 mg/kg of feed. Groups V and VI served as uninfected control groups (ducks of Group VI received T-2 toxin). The body weight gain of the ducks was measured and clinical signs were monitored continuously. The birds were sacrificed and necropsied on days 7, 14, 21, and 28 post infection (PI). The liver, spleen, kidney, thymus, bursa of Fabricius, ileum, caecum and colon were examined histologically. Culturing of Brachyspira spp. and immunohistochemistry were performed from the sampled parts of the intestines as well. No gross pathological or histological lesions that could be associated with B. pilosicoli or B. alvinipulli were detectable in the intestinal mucous membrane including the colonised intestinal glands. Mortality did not occur during the experimental period. Decrease in body weight gain was significant in the T-2-toxin-treated groups, and it was slight (not significant) in the Brachyspira-infected groups. Crust on the beaks, necrosis, crusting and ulceration in the mucous membrane of the oral cavity and on the skin of the feet, atrophy of the thymus and bursa of Fabricius due to the effect of T-2 toxin, accompanied by lymphocyte depletion, were observed. These lesions were most prominent on days 14 and 21 PI but were seen on day 28 PI as well. Immunohistochemical detection and reisolation of B. pilosicoli and B. alvinipulli were successful on days 7, 14, 21 and 28 days from different segments of the intestine of certain birds, but no significant difference was observed in the colonisation rate between the T-2-toxin-treated and the untreated groups.     

Effects of treatment of growing swine with aflatoxin and T-2 toxin

Effects of dietary aflatoxin (AF) and T-2 toxin, singly and in combination, were evaluated in growing crossbred (Yorkshire x Landrace x Hampshire) pigs. The experimental design consisted of 4 treatment groups of 6 barrows each fed diets containing 0 mg of AF and T-2/kg of feed (controls; group 1), 2.5 mg of AF/kg of feed (group 2), 10 mg of T-2/kg of feed (group 3), or 2.5 mg of AF plus 10 mg of T-2/kg of feed (AF + T-2; group 4) ad libitum for 28 days (7 to 11 weeks of age). Production performance, and serum biochemical, and hematologic evaluations were made weekly. Body weight and body weight gain were depressed by all toxin treatments, but the effect of AF and T-2 toxin in combination was less than additive. Liver and kidney weights, as a percentage of body weight, were increased by AF treatment, and heart weight, as a percentage of body weight, was increased by T-2 treatment. Treatment with T-2 toxin induced necrotizing contact dermatitis on the snout, buccal commissures, and prepuce. Consumption of AF resulted in increased serum activities of alkaline phosphatase, aspartate transaminase, cholinesterase, and gamma-glutamyltransferase, and decreased serum concentrations of urea nitrogen, cholesterol, albumin, total protein, calcium, potassium, magnesium, and phosphorus. Consumption of T-2 toxin resulted in increased serum triglyceride concentration and decreased serum iron concentration. Treatment with AF induced lower serum unsaturated iron-binding capacity and high RBC count, PCV, hemoglobin concentration, WBC count, and prothrombin time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscovy ducklings, a particularly sensitive avian bioassay for T-2 toxin and diacetoxyscirpenol

Day-old domesticated Muscovy ducklings (Cairina moshata) were given the trichothecene mycotoxins T-2 toxin or diacetoxyscirpenol at 0.25, 0.5, or 1 micrograms/g of feed for 7 days. All concentrations of both toxins caused characteristic dose-related lesions on the roof of the oral cavity of the birds. Muscovy ducklings showed these signs in a shorter time (less than 16 hours in some cases) and at a lower feed concentration of these trichothecenes than did other avian species in similar studies.     

Infectivity to hosts of the endogenous stages of chicken and murine Cryptosporidium.

Five groups of 4 mice each were inoculated with 10(6) Cryptosporidium muris oocysts. They were necropsied on days 2, 4, 6, 8 and 10. The stomach mucosa from each group were made into 10% suspension in physiological saline and were orally inoculated to 2 mice each. Recipients given suspension from infected mice on day 6, 8 and 10 shed oocysts from 6, 9 and 6, respectively. Similarly, White Leghorn received 10(6) Cryptosporidium sp. oocysts were killed daily between 1 and 6 days. Recipients given bursa of Fabricius or caecum of donor birds on days 4, 5 and 6 shed oocysts. The endogenous stages of murine and chicken Cryptosporidium were able to infect the appropriate host.     

Effects of thyrotropin-releasing hormone and a thyrotropin releasing hormone analog on growth and selected plasma hormones in lambs

An 8-wk growth trial was conducted to assess the effects of continuous infusion of thyrotropin-releasing hormone (TRH) and an active TRH analog less than Aad-His-Pro-NH2 (the less than Aad is L-pyro-alpha-aminoadipic acid) on growth trial performance, carcass composition and hormone profiles of growing lambs. Both drugs were infused at 600 micrograms X lamb -1 X d -1 with 16 lambs/treatment. Both TRH and less than Aad-His-Pro-NH2 decreased average daily gain (ADG; P less than .01) and increased feed conversion (FC; P less than .01) compared with saline infused controls. Average daily feed intake was not altered. Carcasses of lambs given TRH or less than Aad-His-Pro-NH2 contained fewer kilograms of moisture (P less than .05) and appeared to contain fewer kilograms of protein. Thyrotropin-releasing hormone and less than Aad-His-Pro-NH2 increased thyroid gland weights (P less than .05), but pituitary gland weights were not different. Plasma thyrotropin (TSH) concentrations were increased by both drugs compared with control lambs, peaking at 4 to 7 d after initiating infusion. However, by 14 d, TSH concentrations returned to control levels. Triiodothyronine (T3) and thyroxine (T4) were elevated by both drugs over the entire 8-wk trial, with peak levels reached at 10 d and maintained for the duration of the study. Both TRH and less than Aad-His-Pro-NH2 increased prolactin over the entire period. Growth hormone levels were not altered by either drug. The effects of less than Aad-His-Pro-NH2 infusion on growth trial performance, carcass composition and hormone profiles of growing lambs were very similar to TRH. The negative effects of TRH and less than Aad-His-Pro-NH2 infusion on ADG, FC and carcass protein appear to be the result of elevated T3 and T4 levels.