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Establishing a Framework for the Functional Mammary Gland: From Endocrinology to Morphology

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Abstract

From its embryonic origins, the mammary gland in females undergoes a course of ductal development that supports the establishment of alveolar structures during pregnancy prior to the onset of lactogenesis. This development includes multiple stages of proliferation and morphogenesis that are largely directed by concurrent alterations in key hormones and growth factors across various reproductive states. Ductal elongation is directed by estrogen, growth hormone, insulin-like growth factor-I, and epidermal growth factor, whereas ductal branching and alveolar budding is influenced by additional factors such as progesterone, prolactin, and thyroid hormone. The response by the ductal epithelium to various hormones and growth factors is influenced by epithelial–stromal interactions that differ between species, possibly directing species-specific morphogenesis. Evolving technologies continue to provide the opportunity to further delineate the regulation of ductal development. Defining the hormonal control of ductal development should facilitate a better understanding of the mechanisms underlying mammary gland tumorigenesis.

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REFERENCES

  1. G. T. Beatson (1896). On treatment of inoperable carcinoma of the mammal; suggestions for a new method of treatment, with illustrative cases. Lancet 2:104–107, 162–165.

    Google Scholar 

  2. W. Imagawa, G. K. Bandyopadhyay, and S. Nandi (1990). Regulationof mammary epithelial cell growth in mice and rats. Endocr.Rev.11:494–523.

    PubMed  Google Scholar 

  3. B. I. Balinsky (1950). Onthe pre-natal growth of the mammarygland rudiment in the mouse. J.Anat.84:227–235.

    PubMed  Google Scholar 

  4. K. Kratochwil (1969). Organ specificity in mesenchymalinduction demonstrated in the embryonic development of themammary gland of the mouse. Dev.Biol.20:46–71.

    PubMed  Google Scholar 

  5. T. Sakakura (1987). Mammary embryogenesis. In M. C. Neville and C. W. Daniel (eds.),(hhh) The Mammary Gland. Plenum, New York, pp. 37–66.

    Google Scholar 

  6. K. Kimata, T. Sakakura, Y. Inaguma, M. Kato, and Y. Nishizuka (1985). Participation of two different mesenchymesin the developing mouse mammary gland: Synthesisof basement membrane components by fat pad precursor cells. J.Embryol.Exp.Morphol.89:243–257.

    PubMed  Google Scholar 

  7. T. Sakakura, Y. Sakagami, and Y. Nishizuka (1982). Dualorigin of mesenchymal tissues participating in mouse mam-marygland embryogenesis. Dev.Biol.91:202–207.

    PubMed  Google Scholar 

  8. C. H. Knight and M. Peaker (1982). Development of the mammary gland. J.Reprod.Fertil.65:521–536.

    PubMed  Google Scholar 

  9. A. Raynaud (1961). Morphogenesis of the mammary gland. In S. K. Kon and A. T. Cowie (eds.),(hhh) Milk: The Mammary Glandand Its Secretions. Academic Press, New York, pp. 3–46.

    Google Scholar 

  10. L. G. Sheffield (1988). Organization and growth of mammaryepithelia in the mammary gland fat pad. J.Dairy Sci.71:2855–2874.

    PubMed  Google Scholar 

  11. L. Martinet (1962). Embryologie de la mamelle chez le mouton. Ann.Biol.Anim.Biochim.Biophys.2:175–184.

    Google Scholar 

  12. J. Russo and I. H. Russo (1987). Development of the human mammary gland. In M. C. Neville and C. W. Daniel (eds.), The MammaryGland: Development, Regulation and Function. Plenum, New York, pp. 67–93.

    Google Scholar 

  13. A. G. Naccarato, P. Viacava, S. Vignati, G. Fanelli, A. G. Bonadi, G. Montruccoli, and G. Bevilacqua (2000). Biomorphological events in the development of the human female mammary gland from fetal age to puberty. Virchows Arch.436:431–438.

    PubMed  Google Scholar 

  14. G. Mayer and M. Klein (1961). Histology and cytology of the mammary gland. In S. K. Kon and A. T. Cowie (eds.),(hhh) Milk: The Mammary Gland and Its Secretions. Academic Press, New York, pp. 47–116.

    Google Scholar 

  15. R. M. Akers (1990). Lactational physiology: A ruminant animal perspective. Protoplasma 159:96–111.

    Google Scholar 

  16. R. C. Hovey, T. B. McFadden, and R. M. Akers (1999). Regulation of mammary gland growth and morphogenesis by the mammary fat pad: A species comparison. J.Mammary GlandBiol.Neoplasia 4:53–68.

    Google Scholar 

  17. R. C. Hovey, D. E. Auldist, D. D. S. Mackenzie, and T. B. McFadden (2000). Preparation of an epithelium-free mammary fat pad and subsequent mammogenesis in ewes. J.Anim.Sci.78:2177–2185.

    PubMed  Google Scholar 

  18. Y. N. Sinha and H. A. Tucker (1969). Mammary development and pituitary prolactin level of heifers from birth through puberty and during the estrous cycle. J.Dairy Sci.52:507–512.

    PubMed  Google Scholar 

  19. R. M. Akers, T. B. McFadden, S. Purup, M. Vestergaard, K. Sejrsen, and A. V. Capuco (2000). Local IGF-I axis in peripubertal ruminant mammary development. J.MammaryGland Biol.Neoplasia 5:43–51.

    Google Scholar 

  20. B. Heuberger, I. Fitzka, G. Wasner, and K. Kratochwil (1982). Induction of androgen receptor formation by epithelium-mesenchymeinteraction in embryonic mouse mammarygland. Proc.Natl.Acad.Sci.USA 79:2957–2961.

    PubMed  Google Scholar 

  21. K. Kratochwil (1982). The importance of epithelial-stromal interaction in mammary gland development. In M. A. Rich, J. C. Hager, and J. Taylor-Papadimitriou (eds.),(hhh) Breast Cancer: Origins, Detection, and Treatment. Martinus Nijhoff Publishing, Boston, pp. 1–12.

    Google Scholar 

  22. H. D¨urnberger and K. Kratochwil (1980). Specificity of tissue interaction and origin of mesenchymal cells in the androgen response of the embryonic mammary gland. Cell 19:465–471.

    PubMed  Google Scholar 

  23. J. J. Wysolmerski, W. M. Philbrick, M. E. Dunbar, B. Lanske, H. Kronenberg, and A. E. Broadus (1998). Rescue of the parathyroid hormone-related protein knockout mouse demonstrates that parathyroid hormone-related protein is essential for mammary gland development. Development 125:1285–1294.

    PubMed  Google Scholar 

  24. J. Foley, P. Dann, J. Hong, J. Cosgrove, B. Dreyer, D. Rimm, M. Dunbar, W. Philbrick, and J. Wysolmerski (2001). Parathy-roidhormone-related protein maintains mammary epithelialfate and triggers nipple skin differentiation during embryonicbreast development. Development 128:513–525.

    PubMed  Google Scholar 

  25. J. J. Wysolmerski, S. Cormier, W. Philbrick, P. Dann, J.-P. Zhang, J. Roume, A.-L. Delezoide, and C. Silve (2001). Absence of functional type 1 parathyroid hormone(PTH)/PTH-related protein receptors in humans is associ-atedwith abnormal breast development and tooth impaction. J.Clin.Endocrinol.Metab.86:1788–1794.

    PubMed  Google Scholar 

  26. A. Raynaud (1955). Observations sur lles modifications provoquees par les hormones oestrogenes, du mode dedeveloppement des mamelons des foetus de Souris. C.R.Acad.Sci.240:674–676.

    Google Scholar 

  27. A. Raynaud (1950). Recherches experimentales sur le developpementde l'appareil genital et le fonctionementdes glandesendocrines des foetus de souriset de mulot. Arch.Anat.Microsc.Morphol.Exp.39:518–576.

    Google Scholar 

  28. J. F. Couse and K. S. Korach (1999). Estrogen receptor null mice: What have we learned and where will they lead us? Endocr.Rev.20:358–417.

    PubMed  Google Scholar 

  29. G. W. Robinson, A. B. C. Karpf, and Kratochwil (1999). Regulation of mammary gland development by tissue interaction. J.Mammary Gland Biol.Neoplasia 4:9–19.

    PubMed  Google Scholar 

  30. M. E. Dunbar and J. J. Wysolmerski (1999). Parathyroid hormone-related protein: A developmental regulatory molecule necessary for mammary gland development. J.Mammary Gland Biol.Neoplasia 4:21–34.

    PubMed  Google Scholar 

  31. C. S. Freeman and Y. J. Topper (1978). Progesterone is not essential to the differentiative potential of mammary epithelium in the male mouse. Endocrinology 103:186–192.

    PubMed  Google Scholar 

  32. J. A. Myers (1919). Studies on the mammary gland. IV. The histology of the mammary gland in male and femalealbino rats from birth to ten weeks of age. Am.J.Anat.25:395.

    Google Scholar 

  33. R. L. Ceriani (1970). Fetal mammary gland differentiation(hhh) invitro in response to hormones. II. Biochemical findings. Dev.Biol.21:530–546.

    PubMed  Google Scholar 

  34. G. R. Cunha, P. Young, K. Christov, R. Guzman, S. Nandi, F. Talamantes, and G. Thordarson (1995). Mammary phenotypic expression induced in epidermal cells by embryonic mammary mesenchyme. Acta Anat.(Basel).152:195–204.

    Google Scholar 

  35. R. C. Hovey, J. F. Trott, E. Ginsburg, A. Goldhar, M. M. Sasaki, S. J. Fountain, K. Sundararajan, and B. K. Vonderhaar (2001). Transcriptional and spatiotemporal regulation of prolactinreceptor mRNA and cooperativity with progesterone receptor function during ductal branch growth in the mammary gland. Dev.Dyn.222:354–367.

    PubMed  Google Scholar 

  36. M. J. Soares, T. N. Faria, K. F. Roby, and S. Deb (1991). Pregnancy and the prolactin family of hormones: Coordination of anterior pituitary, uterine, and placental expression. Endocr.Rev.12:402–423.

    PubMed  Google Scholar 

  37. M. Freemark, K. Kirk, C. Pihoker, M. Robertson, R. Shiu, and P. Driscoll (1993). Pregnancy lactogens in the rat conceptus and fetus: Circulating levels, distribution of binding, and expression of receptor messenger RNA. Endocrinology 133:1830–1842.

    PubMed  Google Scholar 

  38. L. Ogren and F. Talamantes (1988). Prolactins of pregnancyand their cellular source. Int.Rev.Cytol. 112:1–65.

    PubMed  Google Scholar 

  39. S. Z. Haslam and K. A. Nummy (1992). The ontogeny and cellular distribution of estrogen receptors in normal mouse mammary gland. J.Steroid Biochem.Mol.Biol.42:589–595.

    PubMed  Google Scholar 

  40. S. Z. Haslam (1988). Acquisition of estrogen-dependent progesterone receptors by normal mouse mammary gland. Ontogeny of mammary progesterone receptors. J.SteroidBiochem.31:9–13.

    Google Scholar 

  41. R. L. Maple, R. M. Akers, and K. Plaut (1998). Effects ofsteroid hormone treatment on mammary development in pre-pubertalheifers. Domest.Anim.Endocrinol.15:489–498.

    PubMed  Google Scholar 

  42. S. Ball, K. Polson, J. Emeny, W. Eyestone, and R. M. Akers(2000). Induced lactation in prepubertal holstein heifers. J.Dairy Sci.83:2459–2463.

    PubMed  Google Scholar 

  43. T. B. McFadden, R. M. Akers, and W. E. Beal (1988). Milk protein secretion by explants of prepubertal bull mammary tissue: Breed differences. J.Dairy Sci.71:2904–2914.

    PubMed  Google Scholar 

  44. S. I. Kaplan, M. M. Grumbach, and T. H. Shepard (1972). Theontogenesis of human fetal hormones. I. Growth hormone and insulin. J.Clin.Invest.51:3038–3093.

    Google Scholar 

  45. J. W. Keeling, E. Ozer, G. King, and F. Walker (2000). Oestrogen receptor alpha in female fetal, infant, and child mammary tissue. J.Pathol.191:449–451.

    PubMed  Google Scholar 

  46. J. F. Wiesen, P. Young, Z. Werb, and G. R. Cunha (1999). Signaling through the stromal epidermal growth factor receptoris necessary for mammary ductal development. Development 126:335–344.

    PubMed  Google Scholar 

  47. P. P. Osin (1998). Breast development gives insights into breast disease. Histopathology 33:275–283.

    PubMed  Google Scholar 

  48. T. Mori, H. Nagasawa, and H. A. Bern (1979). Long-term effects of perinatal exposure to hormones on normal and neo-plastic mammary growth in rodents: A review. J.Environ.Pathol.Toxicol.3:191–205.

    PubMed  Google Scholar 

  49. M. Peaker (1991). Production of hormones by the mammary gland: Short review. Endocr.Regul.25:10–13.

    PubMed  Google Scholar 

  50. E. Ginsburg and B. K. Vonderhaar (1995). Prolactin synthesis and secretion by human breast cancer cells. Cancer Res.55:2591–2595.

    PubMed  Google Scholar 

  51. J. A. Mol, E. van Garderen, G. R. Autteman, and A. Rijnberk(1996). New in sights in the molecular mechanism of progestin-induced proliferation of mouse epithelium: Induction of the local biosynthesis of growth hormone (GH) in the mammary glands of dogs, cats and humans. J.Steroid Biochem.Mol.Biol.57:67–71.

    PubMed  Google Scholar 

  52. L. Hilakivi-Clarke, R. Clarke, and M. E. Lippman (1994). Perinatal factors increase breast cancer risk. Breast Cancer Res.Treat.31:273–284.

    PubMed  Google Scholar 

  53. D. Trichopoulos (1990). Hypothesis: Does breast cancer originate in utero?(hhh) Lancet 355:939–940.

    Google Scholar 

  54. A. Ekbom, D. Trichopoulos, H. O. Adami, C. C. Hsieh, and S. J. Lan (1992). Evidence of prenatal influences on breast cancer risk. Lancet 340:1015–1018.

    PubMed  Google Scholar 

  55. A. Ekbom, E. Thurfjell, C. C. Hsieh, D. Trichopoulos, and H. O. Adami (1995). Perinatal characteristics and adult mammographic patterns. Int.J.Cancer 61:177–180.

    PubMed  Google Scholar 

  56. T. C. Rothschild, E. S. Boylan, R. E. Calhoon, and B. K. Vonderhaar (1987). Transplacental effects of diethylstilbestrolon mammary development and tumorigenesis in female ACIrats. Cancer Res.47:4508–4516.

    PubMed  Google Scholar 

  57. A. T. Cowie (1949). The relative growth of mammary glands in normal, gonadectomized and adrenalectomized rats. J.Endocrinol 6:145-157.

    PubMed  Google Scholar 

  58. C. S. Atwood, R. C. Hovey, J. P. Glover, G. Chepko, E. Ginsburg, W. G. Robison, and B. K. Vonderhaar (2000). Pro-gesteroneinduces side-branching of the ductal epitheliumin the mammary glands of peripubertal mice. J.Endocrinol.167:39–52.

    PubMed  Google Scholar 

  59. Y. N. Sinha and H. A. Tucker (1966). Mammary gland growthof rats between 10 and 100 days of age. Am.J.Physiol.210:601–605.

    PubMed  Google Scholar 

  60. J. F. Nelson, K. Karelus, L. S. Felicio, and T. E. Johnson (1990). Genetic influences on the timing of puberty in mice. Biol.Reprod.42:649–655.

    PubMed  Google Scholar 

  61. D. S. Flux (1954). Growth of the mammary duct system in intact and ovariectomized mice of the chitrain. J.Endocrinol.11:223–237.

    PubMed  Google Scholar 

  62. C. W. Daniel and G. Silberstein (1987). Postnatal developmentof the rodent mammary gland. In M. C. Neville and C. W. Daniel (eds.),(hhh) The Mammary Gland: Development, Regulation, and Function. Plenum, New York, pp. 3–36.

    Google Scholar 

  63. N. Zeps, J. M. Bentel, J. M. Papadimitriou, M. F. D'Antuono, and H. J. Dawkins (1998). Estrogen receptor-negative epithelial cells in mouse mammary gland development and growth. Differentiation 62:221–226.

    PubMed  Google Scholar 

  64. R. C. Humphreys (1999). Programmed cell death in the terminalend bud. J.Mammary Gland Biol.Neoplasia 4:213–220.

    PubMed  Google Scholar 

  65. I. H. Russo and J. Russo (1998). Role of hormones in mammary cancer initiation and progression. J.Mammary GlandBiol.Neoplasia 3:49–61.

    Google Scholar 

  66. L. J. Faulkin Jr. and K. B. DeOme(1960). Regulation of growt hand spacing of gland elements in the mammary fat pad of theC3H mouse. J.Natl.Cancer Inst.24:953–963.

    PubMed  Google Scholar 

  67. S. Ellis, F. G. Edwards, and R. M. Akers (1995). Morphologicaland histological analysis of the prepuberal ovine mammarygland. J.Dairy Sci.78(Suppl. 1):202.

    Google Scholar 

  68. T. L. Woodward, W. E. Beal, and R. M. Akers (1993). Cell interactions in initiation of mammary epithelial cell proliferation by oestradiol and progesterone in prepubertal heifers. J.Endocrinol.136:149–157.

    PubMed  Google Scholar 

  69. S. Ellis, S. Purup, K. Sejrsen, and R. M. Akers (2000). Growth and morphogenesis of epithelial cell organoids from peripheral and medial parenchyma of prepubertal heifers. J.DairySci.83:952–961.

    Google Scholar 

  70. C. Wallace (1953). Observations on mammary developmentin calves and lambs. J.Agr.Sci.43:413–421.

    Google Scholar 

  71. R. R. Anderson (1975). Mammary gland growth in sheep. J.Anim.Sci.41:118–123.

    PubMed  Google Scholar 

  72. I. D. Johnsson and I. C. Hart (1985). Pre-pubertal mammo genesis in the sheep. 1. The effects of level of nutrition on growth and mammary development in female lambs. Anim.Prod.41:323–332.

    Google Scholar 

  73. K. Sejrsen and S. Purup (1997). Influence of prepubertal feed-inglevel on milk yield potential of dairy heifers: A review. J.Anim.Sci.75:828–835.

    PubMed  Google Scholar 

  74. A. Dabelow (1941). Der Entfaltungsmechanismus derMamma. II. Die postnatale entwicklung der menschlichenmilchdruse und ihre korrelationen. Morphol.J.85:361–416.

    Google Scholar 

  75. S. Nandi (1958). Endocrine control of mammary gland development and function in the C3H/HeCrgl mouse. J.Natl.Cancer Inst.21:1039–1063.

    PubMed  Google Scholar 

  76. S. Z. Haslam (1988). Local versus systemically mediatedeffects of estrogen on normal mammary epithelial cell deoxyribonucleicacid synthesis. Endocrinology 122:860–867.

    PubMed  Google Scholar 

  77. J. L. Fendrick, A. M. Raafat, and S. Z. Haslam (1998). Mammary gland growth and development from the postnatal period to postmenopause: Ovarian steroid receptor ontogenyand regulation in the mouse. J.Mammary Gland Biol.Neo-plasia 3:7–22.

    Google Scholar 

  78. G. Shyamala and A. Ferenczy (1984). Mammary fat pad maybe a potential site for initiation of estrogen action in normalmouse mammary glands. Endocrinology 115:1078–1081.

    PubMed  Google Scholar 

  79. G. R. Cunha, P. Young, Y. K. Hom, P. S. Cooke, J. A. Taylor, and D. B. Lubahn (1997). Elucidation of a role for stromalsteroid hormone receptors in mammary gland growth and development using tissue recombinants. J.Mammary GlandBiol.Neoplasia 2:393–402.

    Google Scholar 

  80. M. I. Gallego, N. Binart, G. W. Robinson, R. Okagaki, K. T. Coschigano, J. Perry, J. J. Kopchick, T. Oka, P. A. Kelly, and L. Hennighausen (2001). Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects. Dev.Biol.229:163–175.

    PubMed  Google Scholar 

  81. D. L. Kleinberg (1997). Early mammary development: Growth hormone and IGF-1.(hhh) J.Mammary Gland Biol.Neoplasia 2:49–57.

    PubMed  Google Scholar 

  82. M. Feldman, W. Ruan, I. Tappin, R. Wieczorek, and D. L. Kleinberg (1999). The effect of GH on estrogen receptor expression in the rat mammary gland. J.Endocrinol.163:515–522.

    PubMed  Google Scholar 

  83. T. L. Wood, M. M. Richert, M. A. Stull, and M. A. Allar (2000). The insulin-like growth factors (IGFs) and IGF binding proteins in postnatal development of murine mammary glands. J.Mammary Gland Biol.Neoplasia 5:31–42.

    PubMed  Google Scholar 

  84. D. L. Hadsell and S. G. Bonnette (2000). IGFand insulin action in the mammary gland: Lessons from transgenic and knockout models. J.Mammary Gland Biol.Neoplasia 5:19–30.

    PubMed  Google Scholar 

  85. J. P. Lydon, F. J. DeMayo, O. M. Conneely, and B. W. O'Malley(1996). Reproductive phenotypes of the progesterone receptor null mutant mouse. J.Steroid Biochem.Mol.Biol.56:67–77.

    PubMed  Google Scholar 

  86. C. J. Ormandy, N. Binart, and P. A. Kelly (1997). Mammary gland development in prolactin receptor knockout mice. J.Mammary Gland Biol.Neoplasia 2:355–364.

    PubMed  Google Scholar 

  87. C. Brisken, S. Kaur, T. Chavarria, N. Binart, R. L. Sutherland, R. A. Weinberg, P. A. Kelly, and C. J. Ormandy (1999). Prolactin controls mammary gland development via direct and indirect mechanisms. Dev.Biol.210:96–106.

    PubMed  Google Scholar 

  88. C. Brisken, S. Park, T. Vass, J. P. Lydon, B. W. O'Malley, and R. A. Weinberg (1998). A paracrine role for the epithelial progesterone receptor in mammary gland development. Proc.Natl.Acad.Sci.USA 95:5076–5081.

    PubMed  Google Scholar 

  89. R. P. DiAugustine, R. G. Richards, and J. Sebastian (1997). EGF-related peptides and their receptors in mammary glanddevelopment. J.Mammary Gland Biol.Neoplasia 2:109–117.

    PubMed  Google Scholar 

  90. S. Z. Haslam, L. J. Counterman, and K. A. Nummy (1993). Effects of epidermal growth factor, estrogen, and progestin onDNA synthesis in mammary cells(hhh) in vivo are determined by the developmental state of the gland. J.Cell.Physiol.155:72–78.

    PubMed  Google Scholar 

  91. S. Coleman, G. B. Silberstein, and C. W. Daniel (1988). Ductalmorphogenesis in the mouse mammary gland: Evidence supporting a role for epidermal growth factor. Dev.Biol.127:304–315.

    PubMed  Google Scholar 

  92. B. K. Vonderhaar (1987). Local effects of EGF, alpha-TGF, and EGF-like growth factors on lobuloalveolar development of the mouse mammary gland(hhh) in vivo. J.Cell.Physiol.132:581–584.

    PubMed  Google Scholar 

  93. S. M. Snedeker, C. F. Brown, and R. P. Di Augustine (1991). Expression and functional properties of transforming growthfactor a and epidermal growth factor during mouse mammary gland ductal morphogenesis. Proc.Natl.Acad.Sci.USA 88:276–280.

    PubMed  Google Scholar 

  94. L. G. Sheffield and C. W. Welsch (1987). Influence of subman dibular salivary glands on hormone responsiveness of mouse mammary glands. Proc.Soc.Exp.Biol.Med.186:368–377.

    PubMed  Google Scholar 

  95. S. Colemanand C. W. Daniel (1990). Inhibition of mousemam-maryductal morphogenesis and down-regulation of the EGF receptor by epidermal growth factor. Dev.Biol.137:425–433.

    PubMed  Google Scholar 

  96. K. L. Troyer and D. C. Lee (2001). Regulation of mouse mam-marygland development and tumorigenesis by the ERBBsignaling network. J.Mammary Gland Biol.Neoplasia 6:7–21.

    PubMed  Google Scholar 

  97. J. V. Soriano, M. S. Pepper, L. Orci, and R. Montesano (1998). Roles of hepatocyte growth factor/scatter factor and transforming growth factor-beta 1 in mammary gland ductal morphogenesis. J.Mammary Gland Biol.Neoplasia 3:133–150.

    PubMed  Google Scholar 

  98. C. W. Daniel, S. Robinson, and G. Silberstein (1996). The roleof TGF-¯ in patterning and growth of the mammary ductaltree. J.Mammary Gland Biol.Neoplasia 1:331–341.

    PubMed  Google Scholar 

  99. S. Purup, K. Sejrsen, J. Foldager, and R. M. Akers (1993). Effect of exogenous bovine growth hormone and ovariectomyon prepubertal mammary growth, serum hormones andacute in-vitro proliferative response of mammary explantsfrom Holstein heifers. J.Endocrinol.139:19–26.

    PubMed  Google Scholar 

  100. S. Ellis, T. B. McFadden, and R. M. Akers (1998). Prepubertalovine mammary development is unaffected by ovariectomy. Domest.Anim.Endocrinol.15:217–225.

    PubMed  Google Scholar 

  101. A. V. Capuco, R. M. Akers, S. E. Ellis, and D. L. Wood (2000). Mammary growth in Holstein calves: Bromodeoxyuridine incorporation and steroid receptor localization. J.Dairy Sci.83(Suppl. 1):17.

    Google Scholar 

  102. R. C. Hovey, H. W. Davey, D. D. S. Mackenzie, and T. B. McFadden (1998). Ontogeny and epithelialstromal interactions regulate IGF expression in the ovine mammary gland. Mol.Cell.Endocrinol.136:139–144.

    PubMed  Google Scholar 

  103. S. D. Berry, T. B. McFadden, R. E. Pearson, and R. M. Akers(2001). A local increase in the mammary IGF-I: IGFBP-3 ratiomediates the mammogenic effects of estrogen and growth hormone. Domest.Anim.Endocrinol.21:39–53.

    PubMed  Google Scholar 

  104. M. D. Koff and K. Plaut (1995). Expression of transforming growth factor-alpha-like messenger ribonucleic acid transcripts in the bovine mammary gland. J.Dairy Sci.79:1903–1908.

    Google Scholar 

  105. F. Sinowatz, D. Schams, A. Plath, and S. Kolle (2000). Expression and localization of growth factors during mammary gland development. Adv.Exp.Med.Biol.480:19–25.

    PubMed  Google Scholar 

  106. M. O. Thorner, J. Round, A. Jones, D. Fahmy, G. V. Groom,S. Butcher, and K. Thompson (1977). Serum prolactin andoestradiol levels at different stages of puberty. Clin.Endocrinol.(Oxf).7:463–468.

    Google Scholar 

  107. P. A. Lee, T. Xenakis, J. Winer, and S. Matsenbaugh (1976). Puberty in girls: Correlation of serum levels of gonadotropins, prolactin, androgens, estrogens, and progestins with physicalchanges. J.Clin.Endocrinol.Metab.43:775–784.

    PubMed  Google Scholar 

  108. C. Ankarberg-Lindgren, M. Elfving, K. A. Wikland, and E. Norjavaara (2001). Nocturnal application of transdermalestradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls. J.Clin.Endocrinol.Metab.86:3039–3044.

    PubMed  Google Scholar 

  109. A. Pertzelean, L. Yalon, R. Kauli, and Z. Laron (1982). A comparative study of the effect of oestrogen substitution therapy on breast development in girls with hypo-and hyperg-onadotrophichypogonadism. Clin.Endocrinol.(Oxf).16:359–368.

    Google Scholar 

  110. J. Russo, Y. F. Hu, I. D. C. G. Silva, and I. H. Russo (2001). Cancer risk related to mammary gland structure and development. Microsc.Res.Tech.52:204–223.

    PubMed  Google Scholar 

  111. S. A. Bartow (1998). Use of the autopsy to study ontogeny and expression of the estrogen receptor gene in human breast. J.Mammary Gland Biol.Neoplasia 3:37–48.

    PubMed  Google Scholar 

  112. E. Anderson, R. B. Clarke, and A. Howell (1998). Estrogen responsiveness and control of normal human breast proliferation. J.Mammary Gland Biol.Neoplasia 3:23–35.

    PubMed  Google Scholar 

  113. J. Russo, X. Ao, C. Grill, and I. H. Russo (1999). Pattern of distribution of cells positive for estrogen receptor alpha and progesterone receptor in relation to proliferating cells in the mammary gland. Breast Cancer Res.Treat.53:217–227.

    PubMed  Google Scholar 

  114. S. R. Rose, G. Municchi, K. M. Barnes, G. A. Kamp, M. M. Uriarte, J. L. Ross, F. Cassorla, and G. B. Cutler Jr. (1991). Spontaneous growth hormone secretion increases during puberty in normal girls and boys. J.Clin.Endocrinol.Metab.73:428–435.

    PubMed  Google Scholar 

  115. K. J. Cullen, A. Allison, I. Martire, M. Ellis, and C. Singer(1992). Insulin-like growth factor expression in breast cancer epithelium and stroma. Breast Cancer Res.Treat.22:21–29.

    PubMed  Google Scholar 

  116. N. Kawai, S. Kanzaki, S. Takano-Watou, C. Tada, Y. Yamanaka, T. Miyata, M. Oka, and Y. Seino (1999). Serum free insulin-like growth factor I (IGF-I), total IGF-I, and IGF-binding protein-3 concentrations in normal children and children with growth hormone deficiency. J.Clin.Endocrinol.Metab.84:82–89.

    PubMed  Google Scholar 

  117. G. Silberstein and C. W. Daniel (1982). Glycosaminoglycans in the basal lamina and extra cellular matrix of the developing mouse mammary gland. Dev.Biol.90:215–222.

    PubMed  Google Scholar 

  118. C. W. Daniel, J. J. Berger, P. Strickland, and R. Garcia(1984). Similar growth pattern of mouse mammary epithelium cultivated in collagen matrix(hhh) in vivo and(hhh) in vitro. Dev.Biol.104:57–64.

    PubMed  Google Scholar 

  119. H. C. Mertani, T. Garcia-Caballero, A. Lambert, F. Gerard, C. Palayer, J. M. Boutin, B. K. Vonderhaar, M. J. Waters, P. E. Lobie, and G. Morel (1998). Cellular expression of growth hormone and prolactin receptors in human breast disorders. Int.J.Cancer 79:202–211.

    PubMed  Google Scholar 

  120. R. C. Hovey, H. W. Davey, B. K. Vonderhaar, D. D. Mackenzie, and T. B. McFadden (2001). Paracrine action of keratinocyte growth factor (KGF) during ruminant mammo genesis. Mol.Cell.Endocrinol.181:47–56.

    PubMed  Google Scholar 

  121. L. G. Nequin, J. Alvarez, and N. B. Schwartz (1979). Measurement of serum steroid and gonadotropin levels and uterine and ovarian variables throughout 4 day and 5 day estrouscycles in the rat. Biol.Reprod.20:659–670.

    PubMed  Google Scholar 

  122. B. K. Vonderhaar (1988). Regulation of development of thenormal mammary gland by hormones and growth factors. In M. E. Lippman and R. B. Dickson (eds.),(hhh) Breast Cancer: Cellular and Molecular Biology. Kluwer Academic Publishers, Boston, pp. 251–266.

    Google Scholar 

  123. A. Lochter (1998). Plasticity of mammaryepithelia during normal development and neoplastic progression. Biochem.CellBiol.76:997–1008.

    Google Scholar 

  124. J. M. Williams and C. W. Daniel (1983). Mammary ductal elongation, differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev.Biol.97:274–290.

    PubMed  Google Scholar 

  125. M. M. Richert, K. L. Schwertfeger, J. W. Ryder, and S. M. Anderson (2000). An atlas of mouse mammary gland development. J.Mammary Gland Biol.Neoplasia 5:227–241.

    PubMed  Google Scholar 

  126. G. W. Robinson, R. A. McKnight, G. H. Smith, and L. Hennighausen (1995). Mammary epithelial cells undergo secretory differentiation in cycling virgins but require pregnancy for the establishment of terminal differentiation. Development 121:2079–2090.

    PubMed  Google Scholar 

  127. P. Schedin, T. Mitrenga, and M. Kaeck (2000). Estrous cycle regulation of mammary epithelial cell proliferation, differentiation and death in the Sprague-Dawley rat: A model for investigating the role of estrous cycling in mammarycarcinogenesis. J.Mammary Gland Biol.Neoplasia 5:211–225.

    PubMed  Google Scholar 

  128. C. W. Turner and A. E. Gomez (1933). The normal devel-opmentof the mammary gland of the male and female albinomouse. Univ.Mo., Columbia Coll.Agric., Agric.Exp.Stn., Res.Bull.182:1–43.

    Google Scholar 

  129. K. P. Hummel, F. L. Richardson, and E. Fekete (1975). Anatomy. In E. L. Green (ed.),(hhh) Biology of the LaboratoryMouse. Dover Publications, New York, pp. 247–307.

    Google Scholar 

  130. J. E. Fata, V. Chaudhary, and R. Khokha (2001). Cellularturnover in the mammary gland is correlated with systemic levels of progesterone and not 17ß-estradiol during the estrouscycle. Biol.Reprod.65:680–688.

    PubMed  Google Scholar 

  131. H. A. Cole (1934). The mammary gland of the mouse, during the oestrous cycle, pregnancy and lactation. Proc.R. Soc.Lond.B. Biol.Sci.114:136–161.

    Google Scholar 

  132. A.-C. Andres and R. Strange (1999). Apoptosis in the estrous and menstrual cycles. J.MammaryGland Biol.Neoplasia 4:221–228.

    Google Scholar 

  133. R. Dulbecco, M. Henahan, and B. Armstrong (1982). Cell types and morphogenesis in the mammary gland. Proc.Natl.Acad.Sci.USA 79:7346–7350.

    PubMed  Google Scholar 

  134. Y. N. Sinha and H. A. Tucker (1969). Relationship of pituitary prolactin and LH to mammary and uterine growth of pubertal rats during the estrous cycle. Proc.Soc.Exp.Biol.Med.131:908–913.

    PubMed  Google Scholar 

  135. R. E. Grahame and F. D. Bertalanffy (1972). Cell division in normal and neoplastic mammary gland tissue in the rat. Anat.Rec.174:1–8.

    PubMed  Google Scholar 

  136. J. Foldager and K. Sejrsen (1987). Mammary gland development and milk production in dairy cows in relation to feeding and hormone manipulation during rearing. In(hhh) Cattle Produc-tionResearch: Danish Status and Perspectives. Landhushold-ningsselkabetsForlag, Copenhagen, pp. 102–116.

    Google Scholar 

  137. P. Monaghan, N. P. Perusinghe, P. Cowen, and B. A. Gusterson(1990). Peripubertal human breast development. Anat.Rec.226:501–508.

    PubMed  Google Scholar 

  138. H. Vorherr (1974). Development of the female breast. In H. Vorherr (ed.),(hhh) The Breast. Academic Press, New York, pp. 1–18.

    Google Scholar 

  139. P. M. Vogel, N. G. Georgiade, B. F. Fetter, F. S. Vogel, and K. S. McCarty Jr. (1981). The correlation of histologic changes in the human breast with the menstrual cycle. Am.J.Pathol.104:23–34.

    PubMed  Google Scholar 

  140. T. A. Longacre and S. A. Bartow (1986). A correlative mor-phologicstudy of human breast and endometrium in the menstrual cycle. Am.J.Surg.Pathol.10:382–393.

    PubMed  Google Scholar 

  141. J. E. Ferguson, A. M. Schor, A. Howell, and M. W. J. Ferguson (1992). Changes in the extra cellular matrix of the normal human breast during the menstrual cycle. Cell TissueRes.268:167–177.

    Google Scholar 

  142. C. S. Potten, R. J. Watson, G. T. Williams, S. Tickle, S. A. Roberts, M. Harris, and A. Howell (1988). The effect of age and menstrual cycle upon proliferative activity of the normal human breast. Br.J.Cancer 58:163–170.

    PubMed  Google Scholar 

  143. T. J. Anderson, D. J. P. Ferguson, and G. M. Raab (1982). Cell turnover in the “resting” human breast: Influence of parity, contraceptive pill, age and laterality. Br.J.Cancer 46:376–382.

    PubMed  Google Scholar 

  144. D. K. Walmer, M. A. Wrona, C. L. Hughes, and K. G. Nelson (1992). Lactoferrin expression in the mouse reproductive tract during the natural estrous cycle: Correlation with circulating estradiol and progesterone. Endocrinology 131:1458–1466.

    PubMed  Google Scholar 

  145. D. D. DeLeon, M. B. Zelinski-Wooten, and M. S. Barkely(1990). Hormonal basis of variation in oestrous cyclicity inselected strains of mice. J.Reprod.Fertil.89:117–126.

    PubMed  Google Scholar 

  146. M. E. Lieberman, A. Barnea, S. Bauminger, A. Tsafriri, W. P. Collins, and H. R. Lindner (1975). LH effect on the pattern of steroidogenesis in cultured graafian follicles of the rat: Dependence on macromolecular synthesis. Endocrinology 96:1533–1542.

    PubMed  Google Scholar 

  147. R. L. Butcher, W. E. Collins, and N. W. Fugo (1974). Plasma concentration of LH, FSH, prolactin, progesterone and estradiol-17ß throughout the 4-day estrous cycle of therat. Endocrinology 94:1704–1708.

    PubMed  Google Scholar 

  148. P. S. Kalra and S. P. Kalra (1977). Temporal changes in thehypothalamic and serum luteinizing hormone-releasing hormone(LH-RH) levels and the circulating ovarian steroids during the rat oestrous cycle. Acta Endocrinol.(Copenhagen).85:449–455.

    Google Scholar 

  149. F. Bresciani (1968). Topography of DNA synthesis in the mammary gland of the C3H mouse and its control by ovarian hormones: An auto radio graphic study. Cell Tissue Kinet.1:51–63.

    Google Scholar 

  150. S. Z. Haslam (1989). The ontogeny of mouse mammary gland responsiveness to ovarian steroid hormones. Endocrinology 125:2766–2772.

    PubMed  Google Scholar 

  151. S. Z. Haslam (1988). Progesterone effects on deoxyribonucleicacid synthesis in normal mouse mammary glands. Endocrinology 122:464–470.

    PubMed  Google Scholar 

  152. H. Nagasawa and R. Yanai (1971). Increased mammary gland response to pituitary mammotropic hormones by estrogen in rats. Endocrinol.Jpn.18:53–56.

    Google Scholar 

  153. J. P. Lydon, F. J. DeMayo, C. R. Funk, S. K. Mani, A. R. Hughes, C. A. Montgomery Jr., G. Shyamala, O. M.Conneely, and B. W. O'Malley (1995). Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev.9:2266–2278.

    PubMed  Google Scholar 

  154. T. N. Seagroves, J. P. Lydon, R. C. Hovey, B. K. Vonderhaar, and J. M. Rosen (2000). C/EBPß (CCAAT/enhancer binding protein) controls cell fate determination during mammary gland development. Mol.Endocrinol.14:359–368.

    PubMed  Google Scholar 

  155. C. Brisken, A. Heineman, T. Chavarria, B. Elenbaas, J. Tan, S. K. Dey, J. A. McMahon, A. P. McMahon, and R. A Weinberg (2000). Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling. Genes Dev.14:650–654.

    PubMed  Google Scholar 

  156. N. Zeps, J. M. Bentel, J. M. Papadimitriou, and H. J. S. Dawkins (1999). Murine progesterone receptor expression in proliferating mammaryepithelial cells during normal pubertal development and adult estrous cycle: Association with ER®and ERß status. J.Histochem.Cytochem.47:1323–1330.

    PubMed  Google Scholar 

  157. G. Shyamala, X. Yang, G. Silberstein, M. H. Barcellos-Hoff, and E. Dale (1998). Transgenic mice carrying an imbalance in the native ratio of A to B forms of progesterone receptor exhibit developmental abnormalities in mammary glands. Proc.Natl.Acad.Sci.USA 95:696–701.

    PubMed  Google Scholar 

  158. G. Shyamala, X. Yang, R. D. Cardiff, and E. Dale (2000). Impact of progesterone receptor on cell-fate decisions during mammary gland development. Proc.Natl.Acad.Sci.USA 97:3044–3049.

    PubMed  Google Scholar 

  159. N. D. Horseman (1999). Prolactin and mammary gland development. J.Mammary Gland Biol.Neoplasia 4:79–88.

    PubMed  Google Scholar 

  160. B. K. Vonderhaar and A. E. Greco (1979). Lobuloalveolar development of mouse mammary glands is regulated by thyroid hormones. Endocrinology 104:409–418.

    PubMed  Google Scholar 

  161. D. V. Singh and H. A. Bern (1969). Interaction between prolactin and thyroxine in mouse mammary gland lobuloalveolar development(hhh) in vitro. J.Endocrinol.45:579–583.

    PubMed  Google Scholar 

  162. B. K. Vonderhaar (1982). Effect of thyroid hormones on mammary tumor induction and growth. In B. S. Leung (ed.),(hhh) Hormonal Regulation of Experimental Mammary Tumors.Vol.II: Peptides and Other Hormones. Eden Press, Montreal, Canada, pp. 138–154.

    Google Scholar 

  163. A. J. Hackett and H. D. Hafs (1969). Pituitary and hypothalamic endocrine changes during the bovine estrous cycle. J.Anim.Sci.28:531–536.

    PubMed  Google Scholar 

  164. H. D. Hafs and D. T. Armstrong (1968). Corpus luteum growth and progesterone synthesis during the bovine estrous cycle. J.Anim.Sci.27:134–141.

    PubMed  Google Scholar 

  165. D. Schams, I. Rüsse, E. Schallenberger, S. Prokopp, and J. S. D. Chan (1984). The role of steroid hormones, prolactin and placental lactogen on mammary gland development in ewes and heifers. J.Endocrinol.102:121–130.

    PubMed  Google Scholar 

  166. W. J. Fulkerson, G. H. McDowell, and L. R. Fell (1975). Artificial induction of lactation in ewes: The role of prolactin. Aust.J.Biol.Sci.28:525–530.

    PubMed  Google Scholar 

  167. D. Schams (1976). Hormonal control of lactation. In (hhh) Breast-Feedingand The Mother.Ciba Foundation Symposium. Elsevier/Excerpta Medica, New York, pp. 27–48.

    Google Scholar 

  168. S. C. Sud, H. A. Tucker, and J. Meites (1968). Estrogen-progesterone requirements for udder development in ovariectomized heifers. J.Dairy Sci.51:210–214.

    PubMed  Google Scholar 

  169. L. G. Sheffield and I. S. Yuh (1988). Influence of epidermal growth factor on growth of bovine mammary tissue in athymicnude mice. Domest.Anim.Endocrinol.5:141–147.

    PubMed  Google Scholar 

  170. C. Markopoulos, U. Berger, P. Wilson, J.-C. Gazet, and R. C. Coombes(1988). Oestrogen receptor content of normal breastcells and breast carcinomas throughout the menstrual cycle. Br.Med.J. 296:1349–1351.

    Google Scholar 

  171. G. Söderqvist, B. von Schoultz, E. Tani, and L. Skoog (1993). Estrogen and progesterone receptor content in breast epithelial cells from healthy women during the menstrual cycle. Am.J.Obstet.Gynecol.163:874–879.

    Google Scholar 

  172. E. Isaksson, E. von Schoultz, V. Odlind, G. Söderqvist, G. Csemiczky, K. Carlstrom, L. Skoog, and B. von Schoultz (2001). Effects of oral contraceptives on breast epithelial proliferation. Breast Cancer Res.Treat.65:163–169.

    PubMed  Google Scholar 

  173. D. R. Mishell Jr. (1971). Serum gonadotropin and steroid patterns during the normal menstrual cycle. Am.J.Obstet.Gy-necol.111:60–65.

    Google Scholar 

  174. J. Uehara, A. C. Nazario, G. Rodrigues de Lima, M. J. Simoes,Y. Juliano, and L. H. Gebrim (1998). Effects of tamoxifen on the breast in the luteal phase of the menstrual cycle. Int.J.Gynaecol.Obstet.62:77–82.

    PubMed  Google Scholar 

  175. I. J. Laidlaw, R. B. Clarke, A. Howell, W. M. C. Owen, C. S. Potten, and E. Anderson (1995). Proliferation of normal human breast tissue implanted in athymic nude mice is stimulated by estrogen and not progesterone. Endocrinology 136:164–171.

    PubMed  Google Scholar 

  176. M. J. McManus and C. W. Welsch (1984). The effect of estrogen, progesterone, thyroxine, and human placental lactogenon DNA synthesis of human breast ductal epithelium mainta in edin athymic nude mice. Cancer 54:1920–1927.

    PubMed  Google Scholar 

  177. B. von Schoultz, G. Söderqvist, M. Cline, E. von Schoultz, and L. Skoog (1996). Hormonal regulation of the normal breast. Maturitas 23(Suppl.):S23–S25.

    PubMed  Google Scholar 

  178. L. J. Hofseth, A. M. Raafat, J. R. Osuch, D. R. Pathak, C. A. Slomski, and S. Z. Haslam (1999). Hormone replacement therapy with estrogen or estrogen plus medroxyprogesterone acetate is associated with increased epithelial proliferation in the normal postmenopausal breast. J.Clin.Endocrinol.Metab.84:4559–4565.

    PubMed  Google Scholar 

  179. P. Mauvais-Jarvis, F. Kuttenn, and A. Gompel (1986). Antiestrogen action of progesterone in breast tissue. Breast CancerRes.Treat.8:179–187.

    Google Scholar 

  180. C. A. Adejuwon (1991). An analysis of the prolactin surge. Int.J.Gynaecol.Obstet.35:247–253.

    PubMed  Google Scholar 

  181. M. J. McManus and C. W. Welsch (1981). Hormone induced ductal DNA synthesis of human breast tissues mainta in edin the athymic nude mouse. Cancer Res.41:3300–3305.

    PubMed  Google Scholar 

  182. B. K. Vonderhaar (1999). Prolactin involvement in breast cancer. Endocr.-Relat.Cancer 6:389–404.

    PubMed  Google Scholar 

  183. T. Kamalati, B. Niranjan, J. Yant, and L. Buluwela (1999). HGF/SF in mammary epithelial growth and morphogenesis: (hhh) In vitroand (hhh) in vivo models. J.MammaryGland Biol.Neoplasia 4:69–77.

    Google Scholar 

  184. D. G. Fernig, J. A. Smith, and P. S. Rudland (1991). Relationship of growth factors and differentiation in normal and neoplastic development of the mammary gland. Cancer Treat.Res.53:47–78.

    PubMed  Google Scholar 

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  1. Molecular and Cellular Endocrinology Section, Basic Research Laboratory, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland

    Russell C. Hovey, Josephine F. Trott & Barbara K. Vonderhaar

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Hovey, R.C., Trott, J.F. & Vonderhaar, B.K. Establishing a Framework for the Functional Mammary Gland: From Endocrinology to Morphology. J Mammary Gland Biol Neoplasia 7, 17–38 (2002). https://doi.org/10.1023/A:1015766322258

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