Early Mammary Development: Growth Hormone and IGF-1

  • David L. Kleinberg


The first step in pubertal mammary development is the appearance of terminal end buds arising from pleuropotent stem cells present in the immature ductal tree of the prepubertal animal. Work from this laboratory indicates that growth hormone is the pituitary hormone responsible for terminal end bud development. Growth hormone likely acts through the production of IGF-1.3 This minireview focuses on the hormonal control of early mammary development with special emphasis on the roles of growth hormone and IGF-1.

Pleuropotent stem cells pubertal mammary development terminal end bud lactogenesis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 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: Development, Regulation, and Function, Plenum Press, New York, pp. 1–36.Google Scholar
  2. 2.
    I. H. Russo, J. Medado, and J. Russo (1989). Endocrine influences on the mammary gland. In T. C. Jones, U. Mohr, and R. D. Hunt (eds.), Integument and Mammary Glands, Springer-Verlag, Berlin, pp. 252–265.Google Scholar
  3. 3.
    J. Russo and I. H. Russo (1978). DNA-labelling index and structure of the mammary gland as determinants of its susceptibility to carcinogenesis. J. Natl. Cancer Inst. 61:1451.Google Scholar
  4. 4.
    R. P. Reece, C. W. Turner, and R. T. Hill (1936). Mammary gland development in the hypophysectomized albino rat. Proc. Soc. Exp. Biol. Med. 34:204–217.Google Scholar
  5. 5.
    W. U. Gardner and A. White (1941). Mammary growth in hypophysectomized male mice receiving estrogen prolactin. Proc. Soc. Exp. Biol. Med. 48:590–592.Google Scholar
  6. 6.
    A. A. Lewis, E. T. Gomez, and C. W. Turner (1942). Mammary gland development with mammogen I in the castrated and the hypophysectomized rat. Endocrinology 30:37–47.Google Scholar
  7. 7.
    A. E. Wilhelmi (1995). Comparative biochemistry of growth hormone from ox, pig, horse, and sheep pituitaries. In R. W. Smith, O. H. Gaebler, and C. N. H. Long (eds.), Henry Ford Hospital International Symposium on the Hypophyseal Growth Hormone: Nature and Actions, McGraw Hill, New York, pp. 59–69.Google Scholar
  8. 8.
    M. S. Raben (1959). Human growth hormone. Rec. Prog. Horm. Res. 15:71–114.Google Scholar
  9. 9.
    W. R. Lyons, R. E. Johnson, R. D. Cole et al. (1959). Mammary growth and lactation in male rats. In R. W. Smith, O. H. Gaebler, and C. N. H. Long (eds.), The Hypophyseal Growth Hormone, Nature and Actions, McGraw Hill, New York, pp. 461–472.Google Scholar
  10. 10.
    W. R. Lyons, C. H. Li, and R. E. Johnson (1958). The hormonal control of mammary growth and lactation. Rec. Prog. Horm. Res. 14:219–248.Google Scholar
  11. 11.
    W. R. Lyons (1993). Hormonal synergism in mammary growth. Proc. Royal Soc. (London) 149:303–325.Google Scholar
  12. 12.
    S. Nandi (1958). Endocrine control of mammary-gland development and function in the C3 11/HE Crgl mouse. J. Natl. Cancer Inst. 21(6):1039–1062.Google Scholar
  13. 13.
    D. L. Kleinberg, W. Niemann, E. Flamm, P. Cooper, G. Babitsky, and Q. Valensi (1985). Primate mammary development: Effects of hypophysectomy, prolactin inhibition and growth hormone administration. J. Clin. Invest. 75:1943–1950.Google Scholar
  14. 14.
    W. L. J. Lowe (1991). Biological actions of insulin-like growth factors. In D. LeRoith (eds.), Insulin-Like Growth Factors: Molecular and Cellular Aspects (Vol. 3), CRC Press, Boca Raton, pp. 49–86.Google Scholar
  15. 15.
    D. L. Kleinberg, W. F. Ruan, V. Catanese, C. B. Newman, and M. Feldman (1990). Non-lactogenic effects of growth hormone on growth and insulin-like growth factor-I messenger ribonucleic acid of rat mammary gland. Endocrinology 126:3274–3276.Google Scholar
  16. 16.
    M. Feldman, W. Ruan, B. C. Cunningham, J. A. Wells, and D. L. Kleinberg (1993). Evidence that the growth hormone receptor mediates differentiation and development of the mammary gland. Endocrinology 133:1602–1608.Google Scholar
  17. 17.
    W. Ruan, C. B. Newman, and D. L. Kleinberg (1992). Intact and aminoterminally shortened forms of insulin-like growth factor 1 induce mammary gland differentiation and development. Proc. Natl. Acad. Sci. U.S.A. 89:10872–10876.Google Scholar
  18. 18.
    W. Ruan, V. Catanese, R. Wieczorek, M. Feldman, D. L. Kleinberg (1995). Estradiol enhances the stimulatory effect of insulin-like growth factor (IGF-1) on mammary development and growth hormone-induced IGF-1 messenger ribonucleic acid. Endocrinology 136:1296–1302.Google Scholar
  19. 19.
    R. P. C. Shiu and H. G. Friesen (1974). Properties of a prolactin receptor from the rabbit mammary gland. Biochem. J. 140:301–311.Google Scholar
  20. 20.
    R. P. C. Shiu and H. G. Friesen (1980). Mechanisms of action of prolactin in the control of mammary gland function. Ann. Rev. Physiol. 42:83–96.Google Scholar
  21. 21.
    D. R. Glimm, V. E. Baracos, and J. J. Kennelly (1990). Molecular evidence for the presence of growth hormone receptors in the bovine mammary gland. J. Endocrinol. 126:R5–R8.Google Scholar
  22. 22.
    D. W. Leung, S. A. Spencer, R. G. Hammonds, C. Collins, W. J. Henzel, R. Barnard, M. J. Waters, and W. J. Wood (1987). Growth hormone receptor and serum binding protein: purification, cloning, and expression. Nature 330:537–543.Google Scholar
  23. 23.
    S. D. Hauser, M. F. McGrath, R. J. Collier, and G. G. Krivi (1990). Cloning and in vivo expression of bovine growth hormone receptor mRNA. Mol. Cell Endocrinol. 72:187–200.Google Scholar
  24. 24.
    H. Jammes, P. Gaye, L. Belair, and J. Djiane (1991). Identification and characterization of growth hormone receptor mRNA in the mammary gland. Mol. Cell Endocrinol. 75:27–35.Google Scholar
  25. 25.
    D. T. Lincoln, M. J. Waters, W. Breipohl, F. Sinowatz, and P. E. Lobie (1990). Growth hormone receptors expression in the proliferating rat mammary gland. Acta Histochemica Suppl. Band XL:S47–S49.Google Scholar
  26. 26.
    M. Feldman, W. Ruan, and D. L. Kleinberg (1993). Measurement of growth hormone receptor in rat mammary gland. [Abstract] Program 75th Annual Meeting of the Endocrine Society 469A.Google Scholar
  27. 27.
    A. Nilsson, J. Isgaard, A. Lindahl, A. Dahlstrom, A. Skottner, and O. G. P. Isaksson (1986). Regulation by growth hormone of number of chondrocytes containing IGF-1 in rat growth plate. Science 233:571–574.Google Scholar
  28. 28.
    N. L. Schlecter, S. M. Russell, E. M. Spencer, and C. S. Nicell (1986). Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilege in vivo is mediated by local production of somatunedin. Proc. Natl. Acad. Sci. U.S.A. 83:7932–7934.Google Scholar
  29. 29.
    L. J. Murphy, G. I. Bell, and H. G. Friesen (1987). Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat. Endocrinology 120:1279–1282.Google Scholar
  30. 30.
    C. Carlsson-Skwirut, M. Lake, M. Hartmanis, K. Hall, and V. R. Ara (1989). A comparison of the biological activity of the recombinant intact and truncated insulin-like growth factor 1 (IGF-1). Biochim. Biophys. Acta 1011:192–197.Google Scholar
  31. 31.
    M. F. McGrath, R. J. Collier, D. R. Clemmons, W. H. Busby, C. A. Sweeney, and G. G. Krivi (1991). The direct in vitro effect of insulin-like growth factors (IGFs) on normal bovine mammary cell proliferation and production of IGF binding proteins. Endocrinology 129:671–678.Google Scholar
  32. 32.
    D. L. Hadsell, N. M. Greenberg, J. M. Fligger, C. R. Baumrucker, C. R., and J. M. Rosen (1993). Targeted expression of des(1–3) human insulin-like growth factor 1 (IGF-1) in transgenic mice influences mammary gland development and IGF-binding protein expression. Endocrinology 136:(in press).Google Scholar
  33. 33.
    S. Neuenschwander, A. Schwartz, T. L. Wood, C. T. J. Roberts, L. Henninghausen, and D. LeRoith (1996). Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model. J. Clin. Invest. 97:2225–2232.Google Scholar

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • David L. Kleinberg
    • 1
  1. 1.Department of MedicineNew York University Medical Center, and Department of Veterans Affairs Medical CenterNew York

Personalised recommendations