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

Citation
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
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGICAL SCIENCES
ISSN journal
1096-6080 → ACNP
Volume
62
Issue
1
Year of publication
2001
Pages
46 - 53
Database
ISI
SICI code
1096-6080(200107)62:1<46:IUALTW>2.0.ZU;2-U
Abstract
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.