Skip to main content
Log in

Hormonal Control of Alveolar Development and Its Implications for Breast Carcinogenesis

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

During puberty and pregnancy, the breast undergoes major restructuring in order to produce a structure that can secrete and eject copious amounts of milk. By analogy to other branched organs such as the lung or the salivary gland, a large increase in surface area of the specialized epithelium is achieved through repeated ramifications of a system of ducts and alveoli arising from the nipple. In the breast, this process culminates in the appearance of thousands of alveoli or acini, saccular outpouchings from the ductal system. This paper focuses on this final stage of proliferation, the formation of alveolar structures and its control by systemic hormones.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  1. C. W. Daniel and G. B. Silberstein (1987). Postnatal development of the rodent mammary gland. In M. C. Neville and C. W. Daniel (eds.), The Mammary Gland, Plenum, New York, pp. 3–31.

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

  3. W. R. Lyons (1958). Hormonal synergism in mammary growth. Proc.R.Soc.Lond.Ser.B: 303–325.

  4. K. M. Scully, A. S. Gleiberman, Lindzey, D. B. Lubahn, K. S. Korach, and M. G. Rosenfeld (1997). Role of estrogen receptor-alphain the anterior pituitary gland. Mol.Endocrinol.11: 674–681.

    PubMed  Google Scholar 

  5. S. R. Ojeda (1996). Female reproductive function. In J. E. Griffin and S. R. Ojeda (eds.), Textbook of Endocrine Physiology, Oxford University Press, New York, Oxford, pp. 164–200.

    Google Scholar 

  6. Y. N. Ilkbahar, Thordarson, I. G. Camarillo, and F. Talamantes (1999). Differential expression of the growthhormone receptor and growth hormone-binding protein in ep-ithelia and stroma of the mouse mammary gland at various physiological stages. J.Endocrinol.161: 77–87.

    PubMed  Google Scholar 

  7. P. Cohen and R. G. Rosenfeld (1996). Growth regulation. In J. E. Griffin and S. R. Ojeda (eds.), Textbook of Endocrine Physiology, Oxford University Press, New York, Oxford, pp. 244–259.

    Google Scholar 

  8. P. D. Walden, Ruan, M.Feldman, and D. L. Kleinberg (1998). Evidence that the mammary fat pad mediates the action of growth hormone in mammary gland development. Endocrinology 139: 659–662.

    PubMed  Google Scholar 

  9. O. M. Conneely, D. M. Kettelberger, M. J. Tsai, W. T. Schrader, and B. W. O'Malley (1989). The chicken progesterone receptor A and B isoforms are products of an alternate translation initiation event. J.Biol.Chem.264: 14062–14064.

    PubMed  Google Scholar 

  10. C. Brisken, Park, 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.U.S.A.95: 5076–5081.

    PubMed  Google Scholar 

  11. R. C. Humphreys, Lydon, B. W. O'Malley, and J. M. Rosen(1997). Mammary gland development is mediated by both stromaland epithelial progesterone receptors. Mol.Endocrinol.11: 801–811.

    PubMed  Google Scholar 

  12. G. B. Silberstein, Van Horn, Shyamala, and C. W. Daniel (1996). Progesterone receptors in the mouse mammary duct: Distribution and developmental regulation. Cell Growth Differ.7: 945–952.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  14. J. Russo, Ao, 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 [In Process Citation]. Breast Cancer Res.Treat.53: 217–227.

    PubMed  Google Scholar 

  15. R. B. Clarke, Howell, C. S. Potten, and E. Anderson (1997). Dissociation between steroid receptor expression and cell pro-liferationin the human breast. Cancer Res.57: 4987–4991.

    PubMed  Google Scholar 

  16. B. Mulac-Jericevic, R. A. Mullinax, F. J. DeMayo, J. P. Lydon, and O. M.Conneely (2000). Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform. Science 289: 1751–1754.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  19. N. D. Horseman, Zhao, Montecino-Rodriguez, Tanaka, Nakashima, S. J. Engle, Smith, Markoff, and K. Dorshkind (1997). Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the prolactin gene. Embo.J.16: 6926–6935.

    PubMed  Google Scholar 

  20. C. J. Ormandy, Camus, Barra, Damotte, Lucas, Buteau, Edery, Brousse, Babinet, Binart, and P. A. Kelly (1997). Null mutation of the prolactin receptor gene pro-ducesmultiple reproductive defects in the mouse. Genes Dev.11: 167–178.

    PubMed  Google Scholar 

  21. N. Binart, Helloco, C. J. Ormandy, Barra, Clement-Lacroix,N. Baran, and P. A. Kelly (2000). Rescue of pre-implantatoryegg development and embryo implantation inprolactin receptor-deficient mice after progesterone administration. Endocrinology 141: 2691–2697.

    PubMed  Google Scholar 

  22. C. Bole-Feysot, Goffin, Edery, Binart, and P. A. Kelly(1998). Prolactin (PRL) and its receptor: Actions, signal trans-ductionpathways and phenotypes observed in PRL receptorknockout mice. Endocr.Rev.19: 225–268.

    PubMed  Google Scholar 

  23. C. Brisken, Kaur, T. E. Chavarria, Binart, R. L. Sutherland, R. A. Weinberg, P. A. Kelly, and C. J. Ormandy (1999). Prolactincontrols mammary gland development via direct and indirectmechanisms. Dev.Biol.210: 96–106.

    PubMed  Google Scholar 

  24. G. J. Lindeman, Wittlin, Lada, M. J. Naylor, Santamaria, J. G. Zhang, Starr, D. J. Hilton, W. S. Alexander, C. J. Ormandy, and J. Visvader (2001). SOCS1 deficiency resultsin accelerated mammary gland development and rescues lacta-tionin prolactin receptor-deficient mice. Genes Dev.15: 1631–1636.

    PubMed  Google Scholar 

  25. M. I. Gallego, Binart, G. W. Robinson, Okagaki, K. T. Coschigano, Perry, J. J. Kopchick, 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 

  26. Y. Zhou, B. C. Xu, H. G. Maheshwari, He, Reed, M. Lozykowski, Okada, Cataldo, Coschigamo, T. E. Wagner, Baumann, and J. J. Kopchick (1997). A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc.Natl.Acad.Sci.U.S.A.94: 13215–13220.

    PubMed  Google Scholar 

  27. T. A. Jarvinen, Pelto-Huikko, Holli, and J. Isola (2000). Estrogen receptor beta is coexpressed with ER alpha and PR and associated with nodal status, grade, and proliferation rate in breast cancer. Am.J.Pathol.156: 29–35.

    PubMed  Google Scholar 

  28. G. Pelletier and M. El-Alfy (2000). Immuno cytochemical localization of estrogen receptors alpha and beta in the human reproductive organs. J.Clin.Endocrinol.Metab.85: 4835–4840.

    PubMed  Google Scholar 

  29. S. Saji, E. V. Jensen, Nilsson, Rylander, Warner, and J. A. Gustafsson (2000). Estrogen receptors alpha and beta in the rodent mammary gland. Proc.Natl.Acad.Sci.U.S.A.97: 337–342.

    PubMed  Google Scholar 

  30. J. H. Krege, J. B. Hodgin, J. F. Couse, Enmark, Warner, J. F. Mahler, Sar, K. S. Korach, J. A. Gustafsson, and O. Smithies (1998). Generation and reproductive phenotypesof mice lacking estrogen receptor beta. Proc.Natl.Acad.Sci.U.S.A.95: 15677–15682.

    PubMed  Google Scholar 

  31. D. B. Lubahn, J. S. Moyer, T. S. Golding, J. F. Couse, K. S. Korach,and O. Smithies (1993). Alteration of reproductive function butnot prenatal sexual development after insertional disruption ofthe mouse estrogen receptor gene. Proc.Natl.Acad.Sci.U.S.A.90: 11162–11166.

    PubMed  Google Scholar 

  32. J. Lindzey, W. C. Wetsel, J. F. Couse, Stoker, Cooper, and K. S. Korach (1998). Effects of castration and chronic steroid treatments on hypothalamic gonadotropin-releasing hormone content and pituitary gonadotropins in male wild-type and estrogen receptor-alpha knockout mice. Endocrinology 139: 4092–4101.

    PubMed  Google Scholar 

  33. J. F. Couse, D. O. Bunch, Lindzey, D. W. Schomberg, and K. S. Korach (1999). Prevention of the polycystic ovarian phenotype and characterization of ovulatory capacity in the estrogen receptor-alpha knockout mouse. Endocrinology 140: 5855–5865.

    PubMed  Google Scholar 

  34. S. Z. Haslam and G. Shyamala (1979). Effect of oestradiolon progesterone receptors in normal mammary glands and its relationship with lactation. Biochem.J.182: 127–131.

    PubMed  Google Scholar 

  35. Y. Mizoguchi, J. Y. Kim, Enami, and S. Sakai (1997). The regulation of the prolactin receptor gene expression in the mammary gland of early pregnant mouse. Endocr.J.44: 53–58.

    PubMed  Google Scholar 

  36. W. P. Bocchinfuso, J. K. Lindzey, S. C. Hewitt, J. A. Clark, P. H. Myers, Cooper, and K. S. Korach (2000). Induction of mammarygland development in estrogen receptor-alpha knockout mice. Endocrinology 141: 2982–2994.

    PubMed  Google Scholar 

  37. R. A. Huseby, M. J. Soares, and F. Talamantes (1985). Ectopic pituitary grafts in mice: Hormone levels, effects on fertility, and the development of adenomyosis uteri, prolactinomas, and mammary carcinomas. Endocrinology 116: 1440–1448.

    PubMed  Google Scholar 

  38. G. R. Cunha, 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 develop mentusing tissue recombinants. J.Mammary Gland.Biol.Neoplasia 2: 393–402.

    PubMed  Google Scholar 

  39. T. J. Cole, J. A. Blendy, A. P. Monaghan, Krieglstein, Schmid, Aguzzi, Fantuzzi, Hummler, Unsicker, and G. Schutz (1995). Targeted disruption of the glucocorti-coidreceptor gene blocks adrenergic chromaffin cell devel-opmentand severely retards lung maturation. Genes Dev.9: 1608–1621.

    PubMed  Google Scholar 

  40. X. Liu, G. W. Robinson, K. U. Wagner, Garrett, Wynshaw-Boris, and L. Hennighausen (1997). Stat5a is mandatory for adult mammary gland development and lacto genesis. GenesDev.11: 179–186.

    Google Scholar 

  41. D. Jackson, Bresnick, Rosewell, Crafton, Poulsom, Stamp, and C. Dickson (1997). Fibroblast growth factor receptor signalling has a role in lobuloalveolar development of the mammary gland. J.Cell.Sci.110: 1261–1268.

    PubMed  Google Scholar 

  42. D. L. Lacey, Timms, H. L. Tan, M. J. Kelley, C. R. Dunstan,T. Burgess, Elliott, Colombero, Elliott, Scully, Hsu, Sullivan, Hawkins, Davy, Capparelli, Eli, Y. X. Qian, Kaufman, Sarosi, Shalhoub, Senaldi,J. Guo, Delaney, and W. J. Boyle (1998). Osteoprotegerinligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93: 165–176.

    PubMed  Google Scholar 

  43. J. E. Fata, Y. Y. Kong, Li, Sasaki, Irie-Sasaki, R. A. Moorehead, Elliott, Scully, E. B. Voura, D. L. Lacey, W. J. Boyle, Khokha, and J. M. Penninger (2000). The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell 103: 41–50.

    PubMed  Google Scholar 

  44. M. A. Thiede (1989). The mRNA encoding a parathyroid hormone-like peptide is produced in mammary tissue in re-sponseto elevations in serum prolactin. Mol.Endocrinol.3: 1443–1447.

    PubMed  Google Scholar 

  45. 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 

  46. J. Russo and I. H. Russo (1987). Development of the humanmammary gland. In M. C. Neville and C. W. Daniel (eds.), TheMammary Gland, Plenum, New York, pp. 67–93.

    Google Scholar 

  47. S. R. Wellings and H. M. Jensen (1973). On the origin and progression of ductal carcinoma in the human breast. J.Natl.Cancer Inst.50: 1111–1118.

    PubMed  Google Scholar 

  48. J. R. Harris, M. E. Lippman, Veronesi, and W. Willett (1992). Breast cancer (1). N.Engl.J.Med.327: 319–328.

    PubMed  Google Scholar 

  49. J. S. Meyer (1977). Cell proliferation in normal human breastducts, fibroadenomas, and other ductal hyperplasias measuredby nuclear labeling with tritiated thymidine. Effects of menstrual phase, age, and oral contraceptive hormones. Hum.Pathol.8: 67–81.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  51. R. C. Moon (1969). Relationship between previous reproductive history and chemically induced mammary cancer in rats. Int.J.Cancer 4: 312–317.

    PubMed  Google Scholar 

  52. D. Medina, L. E. Peterson, Moraes, and J. Gay (2001). Short-term exposure to estrogen and progesterone induces partial protection against N-nitroso-N-methylurea-induced mammary tumori genesis in Wistar-Furth rats. Cancer Lett.169: 1–6.

    PubMed  Google Scholar 

  53. J. P. Lydon, F. J. DeMayo, C. R. Funk, S. K. Mani, A. R. Hughes, C. A. Montgomery Jr., Shyamala, O. M. Conneely, and B. W. O'Malley (1995). Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev.15: 2266–2278.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brisken, C. Hormonal Control of Alveolar Development and Its Implications for Breast Carcinogenesis. J Mammary Gland Biol Neoplasia 7, 39–48 (2002). https://doi.org/10.1023/A:1015718406329

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015718406329

Navigation