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Toxicologic Pathology
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Invited Review

The Rat Mammary Gland: Morphologic Changes as an Indicator of Systemic Hormonal Perturbations Induced by Xenobiotics

Julia N. Lucas1
Daniel G. Rudmann2
Kelly M. Credille2
Armando R. Irizarry2
Augustine Peter1
Paul W. Snyder1

1 Purdue University Department of Pathobiology, College of Veterinary Medicine, West Lafayette, IN 47907, USA
2 Lilly Research Laboratories, Eli Lilly and Company, Greenfield Laboratories, Greenfield, IN 46140, USA

Correspondence: Address correspondence to: Daniel G. Rudmann, Lilly Research Laboratories, Eli Lilly and Company, Greenfield Laboratories, Greenfield, IN 46140, USA; e-mail:rudmanndg{at}lilly.com

The development and morphology of the rat mammary gland are dependent upon several hormones including estrogens, androgens, progesterone, growth hormone and prolactin. In toxicology studies, treatment with xenobiotics may alter these hormones resulting in changes in the morphology of reproductive tissues such as the mammary gland. In the rat, male and female mammary glands exhibit striking morphologic differences that can be altered secondary to hormonal perturbations. Recognizing these morphologic changes can help the pathologist predict potential xenobiotic-induced perturbations in the systemic hormonal milieu. This review examines the development of the rat mammary gland and the influence of sex hormones on the morphology of the adult male and female rat mammary gland. Specific case examples from the literature and data from our laboratory highlight the dynamic nature of the rat mammary gland in response to hormonal changes.

Key Words: Endocrine disrupters • reproductive system • mammary gland • toxicologic pathology • rat pathology • preclinical safety-assessment/risk management • xenobiotics

Abbreviations: TEB, terminal end bud • E, estrogen • E2, estradiol • IGF-I, insulin -like growth factor one • PRL, prolactin • T, testosterone • P4, progesterone • GH, growth hormone • EGF, epidermal growth factor • DHT, dihydrotestosterone • Er{alpha}, estrogen receptor alpha • Erβ, estrogen receptor beta • SERM, selective estrogen receptor modulator • LH, luteinizing hormone • FSH, follicular stimulating hormone • SD, Sprague-Dawley

Toxicologic Pathology, Vol. 35, No. 2, 199-207 (2007)
DOI: 10.1080/01926230601156260
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