Chronic exposure to anabolic steroids induces the muscle expression of oxytocin and a more than fiftyfold increase in circulating oxytocin in cattle

Abstract

Chronic exposure to anabolic steroids induces the muscle expression of oxytocin and a more than fiftyfold increase in circulating oxytocin in cattle. Physiol Genomics 43: 467-478, 2011. First published February 15, 2011 doi:10.1152/physiolgenomics.00226.2010.-Molecular mechanisms in skeletal muscle associated with anabolic steroid treatment of cattle are unclear and we aimed to characterize transcriptional changes. Cattle were chronically exposed (68 Ϯ 20 days) to a steroid hormone implant containing 200 mg trenbolone acetate and 20 mg estradiol (Revalor-H). Biopsy samples from 48 cattle (half treated) from longissimus dorsi (LD) muscle under local anesthesia were collected. Gene expression levels were profiled by microarray, covering 16,944 unique bovine genes: 121 genes were differentially expressed (DE) due to the implant (99.99% posterior probability of not being false positives). Among DE genes, a decrease in expression of a number of fat metabolism-associated genes, likely reflecting the lipid storage activity of intramuscular adipocytes, was observed. The expression of IGF1 and genes related to the extracellular matrix, slow twitch fibers, and cell cycle (including SOX8, a satellite cell marker) was increased in the treated muscle. Unexpectedly, a very large 21-(microarray) to 97 (real time quantitative PCR)-fold higher expression of the mRNA encoding the neuropeptide hormone oxytocin was observed in treated muscle. We also observed an ϳ50-fold higher level of circulating oxytocin in the plasma of treated animals at the time of biopsy. Using a coexpression network strategy OXTR was identified as more likely than IGF1R to be a major mediator of the muscle response to Revalor-H. A re-investigation of in vivo cattle LD muscle samples during early to mid-fetal development identified a Ͼ128-fold increased expression of OXT, coincident with myofiber differentiation and fusion. We propose that oxytocin may be involved in mediating the anabolic effects of Revalor-H treatment.

Toxicogenomic markers for corticosteroid treatment in beef cattle: Integrated analysis of transcriptomic data

“…The same microarray platform and labeling scheme (singlecolor) was used across all experiments, although microarray slide and labeling kit batches as well as lab operators varied. When microarray data using the same platform, but a scanner at a different resolution in a different lab (De Jager et al, 2011) were included, batch correction was much less reliable (data not shown). Therefore, different scanning protocols and inter-laboratory variation might be a limitation for robust meta-analysis.…”

“…The advent of "omics" technologies (genomics, transcriptomics, proteomics, metabolomics) now offers interesting perspectives to discover reliable and quantifiable markers, which however still await for full implementation in routine analysis. Transcriptome analysis using DNA-microarrays has been recently explored as a screening method to reveal the biological effects of different anabolic compounds and thus support the existing tools to combat the use of these substances in beef cattle (Cannizzo et al, 2013;Carraro et al, 2009;De Jager et al, 2011;Pegolo et al, 2012;Rijk et al, 2010).…”

Local Overexpression of V1a-Vasopressin Receptor Enhances Regeneration in Tumor Necrosis Factor-Induced Muscle Atrophy

“…Interestingly, several authors have shown that exercise, a physiological hypertrophic cue, significantly increases circulating AVP, both in humans and in other mammals, thus posing the theoretical basis for the physiological regulation of muscle hypertrophy by neurohypophyseal hormones [49, 66–69]. De Jager et al recently reported that treatment of cattle with anabolic steroids unexpectedly led to a high expression of mRNA encoding oxytocin in muscle, accompanied by a high level of circulating oxytocin in the plasma [70], suggesting that OT is involved in mediating the anabolic effects of the treatment.…”

17β-estradiol upregulates oxytocin and the oxytocin receptor in C2C12 myotubes

“…Previous studies described the effect of 17 β -estradiol (E2) on the gene expression levels in skeletal muscle of veal calves. In particular, De Jager et al (2011) and Divari et al (2013) demonstrated a strong increase in the expression of the oxytocin ( Oxt ) precursor and oxytocin receptor ( Oxtr ) genes in the skeletal muscle of E2-treated veal calves and an intense raise of the plasmatic concentration of circulating oxytocin peptide (OXT). The high serum OXT concentration was likely due to the estrogen influence on OXT production within the supraoptic and paraventricular nuclei of the hypothalamus and/or its release from the posterior pituitary into the blood stream (Chung, McCabe & Pfaff, 1991; Nomura et al, 2002).…”

“…The high serum OXT concentration was likely due to the estrogen influence on OXT production within the supraoptic and paraventricular nuclei of the hypothalamus and/or its release from the posterior pituitary into the blood stream (Chung, McCabe & Pfaff, 1991; Nomura et al, 2002). Moreover, Oxt precursor gene is increased in bovine skeletal muscle in the late stages of foetal development (De Jager et al, 2011), suggesting that OXT could have a role in muscle growth during both foetal and postnatal development in animals (De Jager et al, 2011; Divari et al, 2013) and that E2 can have a regulatory effect on OXT production in skeletal muscle.…”