Journal Article

<i>In Vitro</i> and <i>in Vivo</i> Effects of 17β-Trenbolone: A Feedlot Effluent Contaminant

Vickie S. Wilson, Christy Lambright, Joe Ostby and L. E. Gray

in Toxicological Sciences

Volume 70, issue 2, pages 202-211
Published in print December 2002 | ISSN: 1096-6080
Published online December 2002 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/70.2.202
In Vitro and in Vivo Effects of 17β-Trenbolone: A Feedlot Effluent Contaminant

More Like This

Show all results sharing these subjects:

  • Medical Toxicology
  • Toxicology (Non-medical)

GO

Show Summary Details

Preview

Concern has arisen regarding the presence and persistence of trenbolone in the environment. Trenbolone acetate is an anabolic steroid used to promote growth in beef cattle. It is hydrolyzed to the active compound, 17β-trenbolone (TB), which is also one of the metabolites excreted by cattle. Reproductive alterations have been reported in fish living in waters receiving cattle feedlot effluent, and in vitro androgenic activity displayed by feedlot effluent samples has been related to these effects. In the current study, the androgenic potency of TB was examined both in vitro and in short-term in vivo assays. TB was a high affinity ligand for the androgen receptor (AR), with an IC50 of about 4 nM in rat ventral prostate cytosol and about 33 nM in cells transfected with the human AR when competed with 1 nM [3H]R1881. TB induced AR-dependent gene expression in MDA-kb2 cells with a potency equal to or greater than dihydrotestosterone. In immunocytochemistry experiments with the human AR, concentrations as low as 1 pM significantly induced androgen-dependent translocation of the AR into the cell nucleus. TB also displayed antiglucocorticoid activity in vitro, inhibiting dexamethasone-induced transcriptional activity, and reduced adrenal gland size in vivo. In the Hershberger assay (in vivo), TB was as potent as testosterone propionate in tissues that lack 5α-reductase but less effective at increasing weight of tissues with this enzyme. Such tissue specificity was anticipated because other C-19 norsteroidal androgens display a similar profile in this assay. Subcutaneous TB treatment was about 50- to 100-fold more effective in stimulating growth of androgen-dependent tissues than was oral treatment. In our in utero screening assay, maternal TB administration increased AGD and attenuated the display of nipples in female offspring in a dose-related manner, similar to the published effects of testosterone propionate. Previous studies have documented that these types of malformations in newborn and infant rats are not only permanent effects but are also highly correlated with serious reproductive malformations as adults. In summary, TB is a potent environmental androgen both in vitro and in vivo and, in contrast to other reports, can induce developmental abnormalities in the fetus.

Keywords: 17β-trenbolone; environmental androgen; feedlot contaminant; in vivo; in vitro; in utero screen

Journal Article.  8615 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.