In utero exposure to the environmental androgen trenbolone masculinizes female Sprague-Dawley rats.
Recently, the occurrence of environmental contaminants with androgenic activity has been described from pulp and paper mill effluents and beef feedlot discharges. A synthetic androgen associated with beef production is trenbolone acetate, which is used to promote growth in cattle. A primary metabolite, 17beta Trenbolone (TB), has been characterized as a potent androgen in both in vitro and in vivo studies with rats. The current study was designed to characterize the permanent morphological and functional consequences of prenatal TB exposure on female rats compared with those produced in an earlier study with testosterone propionate (TP). Female rat offspring were exposed to 0mg/day, 0.1mg/day, 0.5mg/day, 1.0mg/day, or 2.0mg/day TB on gestational days 14-19. The 0.5mg/day, 1.0mg/day, or 2.0mg/day TB groups displayed increases in neonatal anogenital distance (AGD) which persisted in the high dose group. Puberty was delayed in the high dose group and there were increased incidences of external genital malformations and the presence of male prostatic tissue in the 0.5mg/day, 1.0mg/day, or 2.0mg/day groups. These changes were associated with amniotic fluid concentrations of TB that compare favorably with concentrations known to be active in both in vitro systems and in fish.
Hotchkiss
A K
AK
Reproductive Toxicology Division, Endocrinology Branch, MD 72, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Furr
J
J
Makynen
E A
EA
Ankley
G T
GT
Gray
L E
LE
D000653:Amniotic Fluid / Q000737:chemistry; D045930:Anabolic Agents / Q000493:pharmacokinetics / Q000633:toxicity; D000728:Androgens / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D005260:Female; D008431:Maternal-Fetal Exchange; D009558:Nipples / Q000187:drug effects / Q000254:growth & development; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects*; D014204:Trenbolone Acetate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D014621:Vagina / Q000187:drug effects / Q000254:growth & development; D014770:Virilism / Q000139:chemically induced*
D045930:Anabolic Agents; D000728:Androgens; D014204:Trenbolone Acetate