Effects Of Zeranol Research Articles

The effects of zeranol and oestradiol implants on performance and nutrient digestibility of zero-grazed White Fulani cattle

Aim The aim of this study was to investigate the effects of two growth-promoting implants (zeranol and oestradiol-17β) on performance and feed digestibility of finishing White Fulani cattle in the feedlot. This was with a view to determining an alternative means of enhancing cattle performance without grazing the animals. Methods A 60-day feedlot trial was conducted using 27 stocker White Fulani bulls that were allotted randomly to three treatment groups (i.e. non-implanted, oestradiol-implanted and zeranol-implanted) in a completely randomised experimental design. Cattle were offered a compounded feedlot ration consisting of 14% crude protein ad libitum. The bulls were weighed initially and fortnightly thereafter for the duration of the study. Coefficients of dry matter and nutrients digestibility were determined using lignin as an internal marker. Data were analysed using the general linear model procedure of ANOVA and mean values were compared using Fisher’s least significant difference (l.s.d.0.05). Key results The average final liveweight, total weight gain, average daily gain (ADG) and average daily feed intake (ADFI) of implanted feedlot cattle were higher (P < 0.05) than for non-implanted cattle; and higher in oestradiol-implanted cattle compared with zeranol-implanted ones. The ADG was 29.16 and 20.48% higher, and the ADFI was 35.06 and 18.18% higher for oestradiol-implanted and zeranol-implanted feedlot cattle, respectively than for non-implanted cattle. Irrespective of the treatment, feed conversion ratio of experimental bulls remained below the range (4.5–7.5) established for feedlot beef cattle; an indication of better efficiency of feed utilisation by White Fulani cattle. The apparent digestibility of dry matter (59.76–64.31%) of the feedlot ration was in the order: non-implanted = oestradiol-implanted > zeranol-implanted while the apparent digestibility of crude protein (73.91–77.99%) was in the order: non-implanted > oestradiol-implanted = zeranol-implanted. Conclusions and implications The results of this study show that the use of an oestradiol implant in finishing zero-grazed White Fulani cattle was beneficial for improving growth performance. Both implanted and non-implanted cattle showed good coefficients of nutrient digestibility, indicating that the mode of action of the growth implants in enhancing performance characteristics does not depend on indices of digestibility.

Zeranol stimulates proliferation and aromatase activation in human breast preadipocytes.

Aromatase is a crucial enzyme for the biosynthesis of estrogens and is involved in the process of breast carcinogenesis. Concerns have been raised regarding the effects of environmental estrogens as potential regulators of aromatase expression in human breast cells. Zeranol is a non‑steroidal agent with potent estrogenic activity, which is widely used as a growth promoter for cattle in certain countries. The present study hypothesized that aromatase expression and activity may be elevated by low dose zeranol exposure, providing a source of estrogens that may stimulate cell proliferation. In the present study, primary cultured human breast preadipocytes were used as an invitro model. The effects of zeranol on cell proliferation were measured using the MTS assay, aromatase expression levels were determined by immunocytochemical staining and reverse transcription‑polymerase chain reaction, and aromatase enzyme activity and estrogen production were analyzed using corresponding assay kits. The results demonstrated that low dose zeranol (2‑50nM) was able to significantly promote cell proliferation, aromatase mRNA expression, aromatase activity and estrogen production in primary cultured human breast preadipocytes, thus suggesting that zeranol may act as an aromatase activator. The findings of the present study suggest that zeranol promotes breast cancer cell growth by stimulating aromatase activation and increasing estrogen biosynthesis in adipose tissue.

Effect of zeranol on expression of apoptotic and cell cycle proteins in murine placentae

Mycotoxins are chemicals produced by fungus and many of them are toxic to humans. Zeranol is a mycotoxin used to promote growth in cattle in North America; yet such a practice draws concern about the residual compound in meat in European countries. In the present study, the toxicity of zeranol was tested in a mouse model for reproduction. Pregnant ICR mice were given p.o. daily doses of zeranol at 0, 1, 10, 100mg/kg for 4 days (from E13.5 to E16.5). Increased rates of fetal resorption at late gestation (E17.5) and preterm birth (<E18.5) were observed in mice treated with zeranol. The apparent factors causing these perinatal conditions were subsequently investigated. Perturbation of cell death or proliferation-related proteins might deter the growth and maintenance of the placentae, and the subsequent fetal resorption and preterm birth. Placental tissue isolated from pregnant mice at E17.5 showed that the expressions of Cdk2 and 4, Cyclin D1 and Bcl-xL were reduced in zeranol-treatment groups. The downregulations might signify growth or maintenance failure in the placentae. Furthermore, reduction in the signaling proteins Erk-1/2 in the placentae could trigger the decrease in the cell cycle/apoptosis proteins. In addition, relaxin is associated with preterm labor. An increase in placental Relaxin-1 expression could also contribute to early delivery in this study. Result of the current study suggested that exposure to zeranol might introduce adverse effect in pregnancy.

Zeranol Induces Deleterious Effects on the Testes and the Prostate Gland of Mature Rats

Background. Endocrine disrupters have been shown to affect the male and female reproductive systems and to alter potential fertility. Objectives. This study was conducted to evaluate the effect of a continuous-release pellet containing 12 mg of zeranol for 30 days on the testes and the prostate gland of mature male rats. Results. Zeranol treatment induced significant decrease of the testes and the prostate gland weights which were associated with a remarkable atrophy of the testicular seminiferous tubules and prominent regression of the glandular compartment of the prostate gland. However, zeranol treatment increased the thickness of the periductal layer of stromal cells of the prostate gland from a thin layer that express intense immunostaining of SM-actin and mild vimentin to a thicker layer of cells that exhibited intense immunostaining for both SM-actin and vimentin. Conclusion. These findings suggest that zeranol-induced changes to the prostate gland could result from either a direct effect of zeranol on the prostate gland or an indirect effect by interfering with testosterone production through disruption of testicular function.

Abstract 3984: Effect of zeranol on beef skeletal muscle growth by differential image gel electrophoresis (DIGE)

Abstract Zeranol is a resorcylic acid lactone produced by fungi of the genus Fusarium that grows on corn, wheat, barley, oats and sorghum. As such Zeranol is a virtually unavoidable contaminant of crops used to feed animals that are consumed by humans. Zeranol has been shown to have a positive impact on muscle growth during the finishing phase of beef cattle production, was first approved and licensed for use as a growth promotant in cattle and sheep in the USA by FDA in 1969. However, the mechanism of this interaction is unknown but is likely related to changes in muscle specific proteins observable during the increased growth phase during finishing. To determine the affect of Zeranol on beef cattle muscle growth, we performed four DIGE experiments. We compared protein expression level changes between beef cattle treated with Zeranol and untreated beef cattle. On day zero, 10 cattle were implanted with 72 mg of Zeranol pellets, the other half (n = 10) were implanted with vehicle. The beef cattle were raised at the Ohio State University Department of Animal Sciences Beef Barn in accordance with industry standards for 120 days. At 60 days, half the implanted beef cattle and half of the control beef cattle were harvested and the remaining beef cattle were harvested at day 120. Muscle samples were analyzed by DIGE and bioinformatics Seven proteins associated with energy metabolism (creatine kinase, glycogen phosphorylase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglucomutase I, aconitase 2, enolase I, and triosephophate isomerase), 5 proteins with regulation of muscle contraction (slow skeletal muscle troponin T, calsequestrin I, myosin light chains 2 and 3, tropomyosin 3), 3 structural proteins (alpha actin, myosin binding protein C and kelch repeat and BTB domain), a protein associated with myotube formation, dihydrolipoamide dehydrogenase, and HSP70, a protein associated with meat quality, and albumin were identified. The differential regulation of these proteins indicates that muscle growth in cattle implanted with Z is due to fast skeletal muscle. (Supported by NIH grant R01 ES 015212). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3984.

Effect of zeranol or melengestrol acetate (MGA) on testicular and antler development and aggression in farmed fallow bucks.

Fifteen yearling fallow bucks were randomly assigned by BW to one of three treatment groups: control (C; n = 5), melengestrol acetate (MGA; n = 5), and zeranol (Z; n = 5), to evaluate effects on testicular development, aggressive behavior, antler growth, sexual activity, ADG, and BW. Zeranol-treated bucks received zeranol ear implants (36 mg) at 90-d intervals, and MGA-treated bucks received MGA in the ration (100 microg x animal(-1) x d(-1)). Bucks grazed ryegrass/Coastal bermudagrass pasture and were supplemented with 3:1 corn/soybean meal at 0.45 kg x animal(-1) x d(-1). Body weights, body condition scores (BCS), blood samples, and testis measurements were obtained at d 0 and at 14-d intervals for 229 d. As bucks reached hard antler (7/15 to 8/25), antlers were harvested and weighed, and ejaculates were collected at 14-d intervals. Aggression was evaluated using 10-min video sessions scoring body blows, avoidance, head pushes, and head bunts. Scrotal circumference (SC) and paired testis volume were affected by a day x treatment interaction (P < 0.01); testes of zeranol-treated bucks were smaller than those of control or MGA-treated bucks. First sperm in the ejaculate tended to be delayed (P < 0.10) in zeranol-treated bucks compared with control and MGA-treated bucks. Melengestrol acetate-treated bucks had a maximum sperm concentration in the ejaculate that was three times (P < 0.05) that of control bucks and nine times (P < 0.05) that of zeranol-treated bucks. Antler weight was the least (P < 0.01) for bucks receiving zeranol and greatest (P < 0.10) for MGA-treated bucks; intermediate values were recorded for the control bucks. Aggressive behavior was delayed (P < 0.05) for zeranol-treated bucks until treatment effects were overcome. Melengestrol acetate-treated bucks had decreased (P < 0.01) aggressive behavior compared with control bucks. Melengestrol acetate-treated bucks had increased (P < 0.05) serum testosterone concentrations compared with control and zeranol-treated bucks. Human chorionic gonadotropin-stimulated peak serum testosterone concentrations for zeranol-treated bucks were delayed (P < 0.01) compared with control and MGA-treated bucks. Although zeranol-treated bucks overcame treatment effects, they were never able to reach testicular measurements or sperm concentrations equal to those of the control or MGA-treated bucks. Zeranol and MGA treatments may have both positive and negative effects that can be utilized when producing slaughter bucks.

Effect of zeranol on fat deposition and carcass traits in beef heifers

Non-pregnant beef heifers implanted with zeranol at birth and at 100 and 200 d of age were fed a finishing ration for 78 d to slaughter at 21–22 mo of age. Rate of fat deposition, grade fat and marbling score were less (P &lt; 0.05) and carcass weight, rib-eye area and lean-meat yield were greater (P &lt; 0.05) for implanted heifers than for non-implanted heifers. Key words: Zeranol, ultrasound, fat deposition, carcass, beef heifer

Effects of zeranol and two dietary levels of calcium and phosphorus on performance, carcass and bone characteristics, and calcium status in growing lambs.

Seventy-two crossbred wether lambs (average initial weight, 25.1 kg) were used to determine the interaction between zeranol treatment and two dietary levels of Ca and P (.8 and .6% vs .4 and .3% Ca and P, respectively) in a 2 x 2 factorial arrangement on performance, carcass and bone characteristics, and serum concentrations of parathyroid hormone (PTH) and Ca. Lambs were implanted on d 0 and 56 with 12 mg of zeranol. Lambs had ad libitum access to feed for 105 d. On d 99, blood samples were collected. Implanted lambs had 12% greater (P less than .01) daily feed intake, 26% greater (P less than .10) ADG, and a 12% improvement in (P less than .10) feed efficiency compared with nonimplanted lambs. Zeranol-treated lambs had increased (P less than .05) bone cortical area, breaking load, and width of the metacarpal compared with nonimplanted lambs. Lambs fed the .8% Ca and .6% P diet had a higher (P less than .05) percentage of bone ash than lambs fed the .4% Ca and .3% P diet. However, there were no differences (P greater than .05) in the percentage of Ca, P, Mg, or Zn in metacarpal bones due either to higher dietary Ca and P or to implant treatments. Serum concentration of PTH was greater (P less than .10) in lambs fed .8% Ca and .6% P than in those receiving .4% Ca and .3% P. Serum concentrations of PTH and Ca pooled across treatments were greater (P less than .05) before feeding than at 1 h after feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Zeranol on Performance of Steers Grazing High- and Low-Endophyte Tall Fescue Pastures

Steers grazing high- and low-endophyte-infected tall fescue pastures were either not implanted or implanted with 36 or 72mg of zeranol. Zeranol had a greater effect on improving gains of steers grazing high-endophyte tall fescue pastures than on those grazing low-endophyte pastures. Steers implanted with zeranol had lower (P<.05) rectal temperature than nonimplanted steers at d 32. Steers implanted with 72mg of zeranol had lower serum prolactin (P<.05) levels at 32 d than either the control or steers implanted with 36mg zeranol. These findings suggest that zeranol can reduce some of the detrimental effects of endophyte fungus on gains of steers grazing tall fescue pastures during the fall months.

Effect of postweaning implantation of zeranol and dietary energy level on growth and reproductive performance of replacement beef heifers

Eighty-one heifer calves weaned at an average age of 6 mo were used to study the effect of postweaning zeranol implantation, on the growth and reproductive performance of heifers fed to grow slowly on three dietary energy levels. Forty heifers were implanted with 36 mg of zeranol at 30 d and again at 120 d postweaning. The remaining heifers were used as ummplanted controls. Within the implanted and control groups, heifers were subdivided into three groups and fed either a low, medium or high energy diet, which provided approximately 105, 130 and 160%, respectively, of NRC maintenance energy requirement, until 1 yr of age. The heifers were then turned out to pasture with hay supplementation. Heifers were exposed to bulls for 35 d at approximately 14 mo of age. Zeranol had no significant effect on growth. The effect of zeranol on the reproductive traits studied was not significant, although the trend was that the zeranol implanted heifers had lower calf crop born (52.3 vs. 63.6%) and lower incidence of calving difficulty (18.5 vs. 32.1%) than control heifers. The level of energy in the diet had a significant (P &lt; 0.01) effect on growth of the heifers, with those on the high energy diet having the highest mean growth rate, but no significant effect on reproductive performance. Key words: Zeranol, dietary energy, growth, reproduction, heifers

Oral zeranol shortens the prolonged bleeding time of uremic rats

Intravenous conjugated estrogens reduce the prolonged bleeding time in uremic patients and in a rat model of uremia. However, estrogens have major side effects related to their hormonal activity. We investigated whether a beta-resorcylic acid lactone, zeranol (a compound with close spatial similarity to estrogens but with a weak estrogenic activity), improves primary hemostasis in uremic rats and whether the effect is mediated by estrogen receptors. The results showed that single oral administration of zeranol significantly (P less than 0.01) shortened the bleeding time of uremic rats, 20 mg/kg being the minimum effective dose. This effect was long-lasting (72 hours). The dose of 30 mg/kg zeranol reproduced the pattern observed after 20 mg/kg but bleeding time values were still significantly (P less than 0.01) shortened 96 hours after the administration. No changes in hematocrit, platelet and leukocyte count, and serum creatinine were detected after zeranol administration. When uremic rats were pre-treated orally with two estrogen receptor antagonists, tamoxifen and clomiphene (3 mg/kg), zeranol did not shorten the bleeding time, thus suggesting that the hemostatic effect of zeranol was due to an estrogen receptor-mediated mechanisms. These results might have important future implications for the management of uremic bleeding in humans.

The effects of zeranol, an anabolic agent, on the serum immunoglobulins of rabbits immunized with B.19 brucellosis vaccine.

Rabbits were immunized with strain 19 antibrucella vaccine and repeatedly administered zeranol subcutaneously (total dose 10 mg in 28 days). The antibody response was followed up for 14 weeks. The following effects were observed: a) an increase in serum proteins during the period of zeranol treatment; b) increases of the agglutinating and, later, of the complement fixing activity, probably caused by an enhanced antibody avidity; c) an increased production and persistence of IgM (19 S).

Effects of zeranol on in vitro growth hormone release by lamb and rat pituitary cells.

A series of experiments was conducted to evaluate the effect of zeranol on release and synthesis of growth hormone (GH) by anterior pituitary cells established in either static or continuous flow cultures. Young adult male rats, slaughter-age lambs and juvenile lambs were used as sources of pituitary cells. In static primary cell cultures, no consistent effect of zeranol at 10(-7), 10(-9) or 10(-11) M was demonstrated by either rat or ovine cells. Rat pituitaries established in perifusion culture chambers showed no repeatable response to zeranol. Dissociated cells from lambs established in perifusion culture, however, had significant increases in release of GH in response to 37% of zeranol pulse exposures. When dissociated cells from juvenile lamb pituitaries were used, up to 10-fold increases in GH release consistently were measured within minutes of exposure to zeranol.

Effects of zeranol on protein turnover in L6 myotubes

Protein synthesis and degradation were measured in cultures of L6 myotubes to determine the direct anabolic activity of zeranol on muscle. Zeranol, dexamethasone, insulin and zeranol-dexamethasone combination, at various concentrations from 10 −8 to 10 −6M, were added to cultures at either 18 hr prior to or at the beginning of a 6 hr synthesis or degradation measuring period. Protein synthesis was measured by determining the incorporation of radioactivity into trichloraoacetic acid precipitable cell protein following incubation with [ 3H] leucine. Protein synthesis was expressed as cpm incorporated in 6 hr per mg protein. Protein degradation was measured by a pulse-chase procedure using [ 3H] leucine. Protein degradation was expressed as the percent labeled protein degraded in 6 hr. Results from the study indicate that zeranol did not stimulate protein synthesis or inhibit proteolysis (P>.01). Stimulation of proteolysis observed with 10 −8M dexamethasone was 13% and 18% (P<.01) at the 6 hr and 24 hr incubation period, respectively. Dexamethasone-stimulated protein degradation was not altered appreciably by zeranol. In contrast, 10 −6M insulin significantly (P<.01) stimulated protein synthesis (16%) and inhibited protein degradation (15%). These results suggest that the anabolic action of zeranol does not occur by directly regulating muscle protein synthesis or degradation, or by altering the glucocorticoid-induced catabolic response in muscle.

Effects of Zeranol and Trenbolone Acetate on Testis Function, Live Weight Gain and Carcass Traits of Bulls

The ability of zeranol and trenbolone acetate (trenbolone) to alter testis function, weight gain and carcass traits of young bulls was studied. In Exp. 1, the effects of age at initial zeranol implantation was determined. After a 235-d experimental period, sequential implantation (56-d intervals) beginning at 100 or 150 d of age had reduced testis growth (P less than .01), sperm production (P less than .01) and serum testosterone concentration in response to gonadotropin releasing hormone (GnRH; P less than .01). The 200-d age group was partially suppressed, while the 250-d age group was not affected. Body weights were similar to controls in all groups. In Exp. 2, bulls previously implanted with zeranol at 175 and 231 d of age received single implants of zeranol, trenbolone or trenbolone plus zeranol at approximately 300 d of age. At slaughter (135 d later), body weight and carcass characteristics in all treatments were similar to controls. However, trenbolone reduced sperm production (P less than .05), zeranol reduced sperm production and testes weight (P less than .05), but trenbolone plus zeranol was similar to controls. Mean testosterone response to GnRH was suppressed in all implant groups on d 65 (P less than .01), but only in trenbolone or trenbolone plus zeranol groups on d 112 (P less than .05). Results indicate that zeranol suppresses spermatogenesis and testosterone production if implanted before approximately 200 d of age. Reduction of endogenous testosterone without alteration of weight gain or carcass characteristics may be of benefit if behavioral or masculinity traits of bulls are altered. Also, it appears that no benefit is derived from implanting bulls with both trenbolone and zeranol.

The effect of zeranol and testosterone on Merino wethers exposed to highly oestrogenic subterranean clover pasture.

Groups of Merino wethers treated with 2 doses of zeranol (6 mg and 12 mg), or testosterone cyclopentyl propionate (150 mg) and untreated controls were grazed at 2 sites, one an oestrogenic subterranean clover (Trifolium subterraneum) pasture and the other a low oestrogen medic (Medicago truncatula) pasture. The influence of oestrogenic subterranean clover on these treatments was assessed by measuring changes in teat length, bulbourethral gland weight and pathology, bodyweight, carcase weight, dressing percentage and greasy and clean fleece weights. Teat lengths were increased by all treatments except 6 mg of zeranol where increases were not significant, and although increased by exposure to oestrogenic pasture this effect were not additive. Bulbourethral gland weights were increased by both of the zeranol treatments and by oestrogenic pasture, and these effects appeared to be additive. Differences observed histologically indicated that testosterone protected whereas zeranol exacerbated the influence of oestrogen. The bodyweights of all treated groups were heavier than the controls, but carcase weights were not significantly different. However an effect was seen in the group given the 6 mg dose of zeranol on the low oestrogen site, where the dressing percentage was significantly lower than in the control and testosterone treated groups. Differences in greasy and clean fleece weights were not significant except that the washing yield of the testosterone-treated group was significantly lower at the low oestrogen site.

The effects of zeranol on performance and carcass characteristics of young bulls

Kirk and Cooper (1983) reported two experiments in which the growth performance and carcass conformation of intensively fed dairy-bred bulls was improved by sequential implantation with Zeranol®. Two further studies have been conducted in which there has been repeat implantation of Zeranol® and detailed carcass dissection to measure precisely the effects on carcass quality.In trial A, 16 Holstein bull calves were purchased from pedigree breeders and weaned at eight weeks of age, when they were divided into two groups of eight, balanced by weight. From 8 to 12 weeks they were given commercial rearing pellets followed by a. commercial pencil and hay was given ad libitum. From 12 weeks onwards a cereal mix was offered ad libitum, formulated to give 13 MJ/kg dry matter, 160 g/kg crude protein. Hay was withdrawn from 14 weeks of age. At eight weeks of age, half the animals were implanted with 36 mg Zeranol® (Ralgro, Crown Chemical Company, Kent), and re-implanted a further three times every 70 days. Five blood samples were taken from all animals over a 15h period at about 8, 14, 33 and 43 weeks of age.

Effect of zeranol on bull muscle fibre composition

Two trials are reported in which bulls were implanted with zeranol and slaughtered at 18 months. There was no significant change in carcass weight due to zeranol in either trial. Samples of the longissimus dorsi (LD) and splenius (Sp) were cross-cryosectioned, stained for myofibrillar ATPase and examined by conventional light microscopy. The stain resolved three fibre types: I, slow contracting with an oxidative metabolism, IIA, fast-oxidative-glycolytic and IIB, fast-glycolytic. In the LD from treated bulls, the occurrence of IIB fibres was increased, apparently at the expense of IIA fibres, as the occurrence of I fibres was unchanged. These occurrence changes parallelled previously reported effects of castration. Changes in Sp were less dramatic. In one trial IIB fibres were absent from all Sp muscles, but, in the other, some of the Sp muscles from treated animals contained these fibres whereas they were absent from the Sp of the control group. If the changes in fibre type occurrence due to zeranol extend to skeletal muscles other than LD and Sp, there is likely to be a subtle change in the musculature's metabolism. Fibre areas were largely unaffected by zeranol. In this respect zeranol did not mimic castration.

EFFECTS OF ZERANOL ON WEIGHT GAIN, BONE GROWTH AND OTHER CARCASS TRAITS IN STEERS AND BULLS

The effects of zeranol were studied in 24 steers and 24 bulls starting at an average weight of 200 kg for a trial period of 183 days. Bulls grew faster than steers (P = 0.07) and zeranol-treated cattle showed higher average daily gain than controls (P &lt; 0.05); there was no significant interaction between gender and treatment. Castration increased carcass fatness (P &lt; 0.01) and decreased dressing percent (P &lt; 0.01), rib-eye area (P &lt; 0.01), shank muscle (P &lt; 0.01) and shank muscle:bone ratio (P &lt; 0.01). Implantation with zeranol had no effect on these traits. The weights of the radio-ulna, metacarpal and metatarsal bones were not significantly affected by gender or treatment. Growth at the distal end of the radius during the last 2 mo of the experiment was significantly less in treated cattle than in controls (P &lt; 0.01) and in steers than in bulls (P &lt; 0.01). Zeranol resulted in larger pelvic openings (P &lt; 0.01) in bulls and steers and reduced libido (P &lt; 0.05) in treated bulls. Key words: Cattle, zeranol, bone growth, castration, carcass traits, sexual development

Letters to the editor

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