In utero and lactational treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs mammary gland differentiation but does not block the response to exogenous estrogen in the postpubertal female rat
Bc. Lewis et al., In utero and lactational treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs mammary gland differentiation but does not block the response to exogenous estrogen in the postpubertal female rat, TOXICOL SCI, 62(1), 2001, pp. 46-53
These experiments tested whether in utero and lactational exposure to 2,3,7
,8-tetrachlorodibenzo-p-dioxin (TCDD) alters mammary gland differentiation,
estrogen receptor alpha (ER alpha) expression levels, or the response to e
strogen in the female postpubertal rat mammary gland. Pregnant Holtzman rat
s were administered a single oral dose of 1 mug/kg TCDD or vehicle on gesta
tion-day 15, Exposed and non-exposed female offspring were weaned on postna
tal day 21 and ovariectomized at 9 weeks of age. Two weeks later, both TCDD
and control animals were divided into 3 groups, receiving treatment with p
lacebo, 0.025, or 0.1 mg 17 beta -estradiol pellet implants. After 48 h, ma
mmary tissue was removed for analysis following euthanasia. TCDD-exposed ma
mmary glands demonstrated impaired differentiation as measured by the distr
ibution of terminal ductal structures and increased expression levels of ER
alpha, The response to exogenous estrogen was tested in TCDD-exposed anima
ls and compared to control nonexposed animals. Estrogen stimulation of the
TCDD-exposed glands induced progesterone receptor expression and mammary gl
and differentiation as measured by a shift in distribution from terminal en
d buds and terminal ducts to Types I and II lobules, Control glands were be
tter differentiated at baseline and did not exhibit any significant changes
in the distribution of terminal ductal structures following estrogen stimu
lation. The increase in progesterone receptor-expression levels by exogenou
s estrogen in control glands was similar to the TCDD-exposed glands. These
experiments demonstrate that in utero and lactational exposures to TCDD imp
air mammary gland differentiation but that TCDD-exposed mammary glands reta
in the ability to differentiate in response to estrogen.