Expression profiling of skeletal muscle in young bulls treated with steroidal growth promoters

Abstract

Dexamethasone (Dex), alone or in association with estrogens, is often illegally administered per os at very low dosage as a growth promoter in beef cattle, with effects that are opposite to the muscle wasting and atrophy induced by repeated administration at therapeutic dosages. In vitro and in vivo studies have investigated the catabolic effects of Dex at therapeutic doses on skeletal muscle, demonstrating an increase in the expression of GDF8 (myostatin) gene, a well-known negative regulator of skeletal muscle mass, in a dose-dependent way. This suggested a direct role of myostatin in Dex-induced muscle wasting. In the present study, an oligonucleotide microarray platform was used to compare expression profiles of beef cattle muscle in animals treated with either Dex or Dex plus 17-β estradiol (Estr) administered at subtherapeutic dosage, against untreated controls. Data analysis demonstrates that the expression profiles were strongly affected by Dex treatment with hundreds of genes upregulated with relevant fold-change, whereas seven genes were downregulated including the myostatin gene. On the contrary, the number of differentially regulated genes was lower in response to the addition of Estr to the Dex treatment. Differentially regulated genes were analyzed to describe the effects of these treatments on muscle physiology, highlighting the importance of specific pathways (e.g., Wnt or cytokine signaling) and cellular processes (e.g., cell shape and motility). Finally, the observed differences in the expression profile will allow the development of indirect bio-markers to detect illegal Dex treatments in beef cattle using quantitative RT-PCR.

A Histologic Study on Growth Promoter Target Organs of Slaughtered Beef in Molise Region (Italy)

“…For this reason, in addition to the traditional chemical analysis, which can give unsatisfactory results [25], other auxiliary diagnostic approaches to detect illegally treated animals are based on anatomo-histopathological examination of target organs [1]. Recently, biotechnological approaches [4,33] to the research of biomarkers, mainly with biomolecular methods, have been suggested [8,13,17,39].…”

Scientific Opinion on the public health hazards to be covered by inspection of meat (bovine animals)

“…betamethasone, dexamethasone, methylprednisolone and prednisolone, are approved for use as VMPs in bovine animals and, therefore, have associated withdrawal periods and MRLs. In addition to their therapeutic uses, corticosteroids, when used at low dosages, are reported to increase appetite, weight gain and feed efficiency, as well as skeletal muscle mass and carcass characteristics (Courtheyn et al, 2002;Tarantola et al, 2004;Carraro et al, 2009). Table 7 shows the data for non-compliant results for corticosteroids in bovine samples in the NRCP for the period 2005-2010.…”

Scientific Opinion on the public health hazards to be covered by inspection of meat (solipeds)

“…Only one of the corticosteroids, dexamethasone is approved for use as a VMP in solipeds and, therefore, has associated withdrawal periods and MRLs. In addition to their therapeutic uses, corticosteroids, when used at low dosages, are reported to increase appetite, weight gain and feed efficiency, as well as skeletal muscle mass and carcass characteristics (Courtheyn et al, 2002;Tarantola et al, 2004;Carraro et al, 2009). Testing of samples for corticosteroids was undertaken by most MSs under group B2f-Other pharmacologically active substances, but a number of countries tested for corticosteroids under group A3-Steroids as this 43 Council Directive 96/22/EC of 29 April 1996 concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of beta-agonists, and repealing Directives 81/602/EEC, 88/146/EEC and 88/299/EEC.…”

“…Only one of the corticosteroids, dexamethasone is approved for use as a VMP in solipeds and, therefore, has associated withdrawal periods and MRLs. In addition to their therapeutic uses, corticosteroids, when used at low dosages, are reported to increase appetite, weight gain and feed efficiency, as well as skeletal muscle mass and carcass characteristics (Courtheyn et al, 2002; Tarantola et al, 2004;Carraro et al, 2009 Considering that, while corticosteroids may be effective for growth promotion in solipeds, the results for the NRCP 2005-2010 do not indicate that there is widespread use of these substances as illicit growth promoters. Therefore, corticosteroids currently are ranked as being of low potential concern.…”