Increase of oxytocin-induced oscillatory contractions by 4-hydroxy- 2',4',6'-trichlorobiphenyl is fstrogen receptor mediated

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that are associated with decreased gestation length in women as well as other mammals. Many lightly chlorinated PCBs are hydroxylated in vivo. The PCB congener 4-hydroxy-2',4',6'-trichlorobiphenyl (4-OH-TCB) has a high affinity for estrogen receptors and exerts a uterotropic effect in vivo. This study tested the hypothesis that 4-OH-TCB increases the contractile response of midgestation uteri to oxytocin by an estrogen receptor-mediated mechanism. After in vitro treatments with 4-OH-TCB or estradiol-17β for 20 h or 42 h, uterine explants from midgestation rats were mounted in standard muscle baths for measurement of isometric contractions. A 20-h exposure to either 4-OH-TCB (0.1, 1, or 10 μM) or estradiol-17β (10 nM) failed to alter the contractile response to cumulative additions of oxytocin (10^-10 to 10^-7 M). However, a 42-h exposure to either 1 μM 4-OH-TCB or 10 nM estradiol-17β significantly elevated the contractile response to oxytocin, which was abolished by cotreatment with the estrogen receptor antagonist tamoxifen (30 nM). These data support the hypothesis that the stimulatory actions of estradiol-17β and 4-OH-TCB on oxytocin-induced oscillatory contractions are mediated by estrogen receptors. Under the conditions of this experiment, more than 20 h of treatment is required to elicit the estrogen- dependent responses.