Fate of radioactive melengestrol acetate in the bovine

Krzeminski, Leo F.; Cox, Byron L.; Gosline, Ronald E.

doi:10.1021/jf00104a041

Cited by 21 publications

(10 citation statements)

References 2 publications

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“…Past research in which radioactive testosterone was administered to cross-bred steers, and radioactive MGA administered to heifers demonstrated, in each case, that most of the label is excreted in the feces [Gassner et al, 1960;Krzeminski et al, 1981]. Therefore, pooled samples from pretreated and treated MGA fecal extracts were analyzed by HPLC.…”

Section: Mgamentioning

confidence: 99%

Aggression control in a bachelor herd of fringe‐eared oryx (Oryx gazella callotis), with melengestrol acetate: Behavioral and endocrine observations

et al. 2001

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Aggression control is becoming an important component in the management of animals in captivity, but rigorous quantification of aggressive behavior has heretofore been lacking. This study was done to assess the ability of melengestrol acetate (MGA) given with feed (1.54 mg/kg) to control aggression in a bachelor group of fringe-eared oryx (Oryx gazella callotis). Systematic behavioral observations were conducted and fecal androgen content was measured for 42 and 90 days, respectively, before treatment, and during the 42 days of treatment. There was a significant reduction in concentrations of fecal androgen from 153 ± 6.0 to 95 ± 4.5 ng/g (T 66 = 7, P < 0.0001). This reduction in androgen excretion was apparent after the first week of treatment. There was measurable MGA excreted in the feces during treatment. Although treatment did not arrest all aggressive behaviors among animals, the decline in androgens and increase in MGA was accompanied by a significant reduction in several measures of agonistic behavior. Posturing, aggressive contact, pursuit, and submission occurred significantly less frequently after treatment, and there was also a reduction in fighting-intention movements. Thus, both ritualized and nonritualized aspects of aggression were affected. Reductions in hormones and aggressive behaviors coincided temporally, suggestive of a potential causal relationship. Consistent with this hypothesis is a strong positive correlation between fecal androgen and total aggressive acts. This effect was not the result of a single behavioral element but occurred across several categories of agonistic behavior. Zoo Biol 20:375-388, 2001. INTRODUCTIONIn male ungulates, it has been suggested that there is a causal link between aggressive behavior and androgens [Bouissou, 1983]. A synthetic progestogen, melengestrol acetate (MGA), originally developed as an orally active contraceptive [Kirk et al., 1962], has been reported to decrease aggression in three ungulate species. Silastic implants containing MGA reduced intraspecific aggression in bachelor herds of scimitar-horned oryx, Oryx dammah [Blumer et al., 1992]. Male muntjacs (Muntiacus reevesi) fed MGA had significantly decreased sperm numbers, and anecdotal reports of behavior indicated reduced aggression [Stover et al., 1987]. Orally administered MGA reduced aggression during the early rut in farmed fallow bucks (Dama dama) [Wilson et al., 2000]. None of these studies, however, systematically quantified aggression before and after MGA administration, leaving the question of efficacy unresolved.The fringe-eared oryx (Oryx gazella callotis), an east African subspecies of the gemsbok (Oryx gazella), is a horselike antelope that lives in the harsh arid environments of east Africa. This species has no particular breeding season. Most frequently, territorial males breed females in their postpartum estrus. Herds of bachelor males are seldom found [Price, 1986;Wacher, 1988]. In captivity, however, it is sometimes necessary to hold males in all-male groups. Elevated aggres...

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Section: Mgamentioning

confidence: 99%

Aggression control in a bachelor herd of fringe‐eared oryx (Oryx gazella callotis), with melengestrol acetate: Behavioral and endocrine observations

et al. 2001

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“…MGA metabolism in cattle remains unclear: according to one study reported by employees of an MGA sponsor, the percentage of total residue accounted for by MGA was 29 % in the liver and kidney, 48 % in muscle, and 84 % in fat [62]. A number of metabolites were detected but not identified.…”

Section: Melengestrol Acetatementioning

confidence: 99%

Hormone Use in Food Animal Production: Assessing Potential Dietary Exposures and Breast Cancer Risk

Nachman

Smith

2015

Curr Envir Health Rpt

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In recent years, increasing attention has been paid to the role of hormones in breast cancer etiology, following reports that heightened levels of endogenous hormones and exposure to exogenous hormones and other endocrinedisrupting chemicals through food and the environment are associated with increased breast cancer risk. Seven hormone drugs (testosterone propionate, trenbolone acetate, estradiol, zeranol, progesterone, melengestrol acetate, and bovine somatotropin) are approved by the U.S. Food and Drug Administration for use in food animals. There is concern that these drugs or their biologically active metabolites may accumulate in edible tissues, potentially increasing the risk of exposure for consumers. To date, the potential for human exposure to residues of these compounds in animal products, as well as the risks that may result from this exposure, is poorly understood. In this paper, we discuss the existing scientific evidence examining the toxicological significance of exposure to hormones used in food animal production in relation to breast cancer risk. Through a discussion of U.S. federal regulatory programs and the primary literature, we interpret the state of surveillance for residues of hormone drugs in animal products and discuss trends in meat consumption in relation to the potential for hormone exposure. Given the lack of chronic bioassays of oral toxicity of the seven hormone compounds in the public literature and the limitations of existing residue surveillance programs, it is not currently possible to provide a quantitative characterization of risks that result from the use of hormonal drugs in food animal production, complicating our understanding of the role of dietary hormone exposure in the population burden of breast cancer.

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“…Studies on the fate of MGA in cattle were conducted by Krzeminski et al (8) using radioactive MGA labeled with tritium in the 6methyl group or with 14 C in the 6-methyl and 16-methylene group. Moreover, the disposition of a single dose of MGA (radiolabelled with 14 C in the 6-methyl group) in women was reported in an abstract by Cooper et al (9).…”

Section: Melengestrol Acetatementioning

confidence: 99%

Genotoxic potential of xenobiotic growth promoters and their metabolites

Metzler

Pfeiffer

2001

APMIS

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potential of xenobiotic growth promoters and their metabolites. APMIS 2001;109:89-95.This paper reviews data reported in the literature as well as recent and unpublished studies from our laboratory on the metabolism and genotoxicity of the xenobiotic growth promoters 17b-trenbolone, melengestrol acetate and zeranol. In our metabolic study, the oxidative in vitro metabolites generated by hepatic microsomes from rats, bovine and humans were analyzed by HPLC and GC/MS. 17b-Trenbolone gave rise to at least 13 monohydroxylated products, whereas 12 mono-and dihydroxylated metabolites were obtained with melengestrol acetate and at least 5 with zeranol. The genotoxic potential of the parent compounds was studied using the following endpoints: induction of HPRT mutations in cultured V79 cells and of lacI mutations in E. coli; induction of micronuclei in V79 cells; and formation of DNA adducts in cultured primary rat hepatocytes. Negative results were obtained in most of these assay systems. Only the micronucleus induction was marginally positive with 17btrenbolone and zeranol at near-cytotoxic concentrations. Commercial melengestrol acetate was found to contain an impurity causing apoptosis in V79 cells. The genotoxic potential of the numerous oxidative metabolites of the xenobiotic growth promoters remains to be studied.

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Fate of radioactive melengestrol acetate in the bovine

Cited by 21 publications

References 2 publications

Aggression control in a bachelor herd of fringe‐eared oryx (Oryx gazella callotis), with melengestrol acetate: Behavioral and endocrine observations

Aggression control in a bachelor herd of fringe‐eared oryx (Oryx gazella callotis), with melengestrol acetate: Behavioral and endocrine observations

Hormone Use in Food Animal Production: Assessing Potential Dietary Exposures and Breast Cancer Risk

Genotoxic potential of xenobiotic growth promoters and their metabolites

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