Assessing the mammary gland of nonhuman primates: effects of endogenous hormones and exogenous hormonal agents and growth factors

Abstract

This review provides a summary of the normal biology, development, and morphology of the breast in nonhuman primates (macaques), and of the major published work addressing hormonally-induced changes in the breast of these animals. The mammary glands of macaques are anatomically, developmentally, and physiologically similar to the human breast, with similar expression of sex steroid receptors (estrogen receptors alpha and beta, progesterone receptor A and B, androgen receptors), estrogen dependent markers, and steroid metabolizing enzymes. Genetic similarity between human beings and macaques is high, varying from 95-99% depending on the sequence evaluated. Macaques develop hyperplastic and cancerous lesions of the breast spontaneously, which are similar in type and prevalence to those of human beings. They have a reproductive physiology typical of anthropoid primates, including a distinct menarche and menopause, and a 28-day menstrual cycle. These similarities give unique value to the macaque model for evaluation of the effectiveness and safety of hormonal agents. Such agents considered in this review include estrogens and progestogens, combined therapies such as oral contraceptives and post-menopausal hormone therapies, androgens, selective estrogen receptor modulators, phytoestrogens, prolactin, somatotropin, epidermal growth factor, and other novel agents with hormonal or growth factor-like activity. This review also includes a consideration of selected background changes and typical strategies and markers used for evaluation of experimentally-induced changes, including biopsy-based strategies designed to control for inter-individual variability and minimize numbers of animals used.