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Toxicologic Pathology
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Articles

The Mammary Glands of Macaques

J. Mark Cline1 and Charles E. Wood1

1 Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

Correspondence: J. Mark Cline, DVM, PhD, DACVP, Professor of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040, USA. Phone: (336) 716-1564; fax: (336) 716-1515; e-mail:jmcline{at}wfubmc.edu.

This review describes the normal biology and physiology of the mammary gland in macaques, including the typical histologic appearance across the life span (development, reproductive maturity, lactation, and senescence). The molecular events regulating breast morphogenesis are described, as well as systemic and local hormonal regulators of mammary gland proliferation, differentiation, and function. Similarities and differences to the human breast are described. Regulatory events are illuminated by discussion of genetically modified mouse models. Tissue response markers, including immunohistochemical markers of proliferation and other hormonally induced changes and studies to date, regarding the effects of exogenous hormones, are briefly summarized. In general, estrogens stimulate progesterone receptor expression and proliferation in the mammary gland, and combinations of estrogens and progestogens cause greater proliferation than estrogens alone. Evaluation of novel chemical agents in macaques requires careful evaluation of age and hormonal context to avoid the confounding effects of mammary gland development, past reproductive history, and other influences on mammary gland morphology. The expression of proliferation markers and progesterone receptors may be used as biomarkers to measure chemically induced hormonal effects.

Competing Interests: This article was sponsored by Covance Inc. and Schering-Plough. The authors did not declare any other competing interests.

Key Words: primate pathology • mammary gland • estrogen • progesterone • proliferation • receptors • development

Abbreviations: CEE, conjugated equine estrogens • GH, growth hormone • IGF, insulin-like growth factor • MPA, medroxyprogesterone acetate • NMGA, nomegestrol acetate • NETA, norethindrone acetate • Laso, lasofoxifene • Tam, tamoxifen • Ral, raloxifene • SERM 393 and 379, investigative selective estrogen receptor modulators

Toxicologic Pathology, Vol. 36, No. 7 Suppl, 130S-141S (2008)
DOI: 10.1177/0192623308327411
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