Effects of Neonatal Exposure to Diethylstilbestrol, Tamoxifen, and Toremifene on the BALB/c Mouse Mammary Gland

• Published in: Biology of reproduction Vol. 72; no. 2; pp. 423 - 435
• Main Authors: HOVEY, Russell C, ASAI-SATO, Mikiko, WARRI, Anni, TERRY-KOROMA, Barbara, COLYN, Nira, GINSBURG, Erika, VONDERHAAR, Barbara K
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01.02.2005
• Subjects: Aging - physiology; Animals; Animals, Newborn - physiology; Biological and medical sciences; Blotting, Western; Diethylstilbestrol - pharmacology; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Estrogen Antagonists - pharmacology; Estrogens, Non-Steroidal - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Genitalia, Female - drug effects; Genitalia, Female - growth & development; Hormones - blood; Immunohistochemistry; In Situ Hybridization; Lactation - drug effects; Mammary Glands, Animal - drug effects; Mammary Glands, Animal - growth & development; Medical sciences; Mice; Mice, Inbred BALB C; Organ Culture Techniques; Ovariectomy; Pharmacology. Drug treatments; RNA - biosynthesis; RNA - genetics; RNA - isolation & purification; Tamoxifen - pharmacology; Toremifene - pharmacology; Toxicity: urogenital system; Vertebrates: reproduction; Agonist; Neonatal; Antiestrogen; Estrogen; Rodentia; Antihormone; Ovarian hormone; Vertebrata; Reproduction; Mammalia; Mouse; Animal; Toremifene; Diethylstilbestrol; Mammary gland; Sex steroid hormone; Non steroid compound; Hormonal receptor
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.104.029769

In this study, we compared the long-term effects of neonatal exposure to diethylstilbestrol (DES, 0.0125–50 μg), tamoxifen (TAM, 0.0125–50 μg), and toremifene (TOR, 53 μg) on mammary gland development and differentiation. Allometric growth of the mammary ducts was stimulated by neonatal DES exposure (12.5 μg) and impaired by exposure to TAM (25 μg). Neonatal treatment with high doses of DES resulted in mammary ducts that displayed extensive dilatation and precocious lactogenesis in postpubertal, nulliparous females. Initiation of this precocious differentiation coincided with the absence of corpora lutea, increased levels of serum prolactin (PRL), and the induction of Prl mRNA expression within the mammary glands. Neonatal exposure to 1.25 μg TAM increased alveolar development in postpubertal, nulliparous females similar to that recorded in females treated with low doses of DES. Lower doses of TAM did not affect alveolar development, whereas branching morphogenesis and alveolar development were impaired by higher doses. Increased alveolar development in females exposed to 1.25 μg TAM was associated with elevated serum progesterone (P) and increased alveolar development in response to exogenous P. Taken together, our findings demonstrate that neonatal exposure to both DES and TAM exerts long-lasting effects on the proliferation and differentiation of the mammary glands in female BALB/c, primarily as the result of endocrine disruption Abstract Neonatal exposure to diethylstilbestrol or tamoxifen has dose-dependent effects on mammary function