Hormonal Regulation of Mammary Differentiation and Milk Secretion

Abstract

The endocrine system coordinates development of the mammary gland with reproductive development and the demand of the offspring for milk. Three categories of hormones are involved. The levels of the reproductive hormones, estrogen, progesterone, placental lactogen, prolactin, and oxytocin, change during reproductive development or function and act directly on the mammary gland to bring about developmental changes or coordinate milk delivery to the offspring. Metabolic hormones, whose main role is to regulate metabolic responses to nutrient intake or stress, often have direct effects on the mammary gland as well. The important hormones in this regard are growth hormone, corticosteroids, thyroid hormone, and insulin. A third category of hormones has recently been recognized, mammary hormones. It currently includes growth hormone, prolactin, PTHrP, and leptin. Because a full-term pregnancy in early life is associated with a reduction in breast carcinogenesis, an understanding of the mechanisms by which these hormones bring about secretory differentiation may offer clues to the prevention of breast cancer.

This is a preview of subscription content, access via your institution.

REFERENCES

  1. 1.

    R. C. Hovey, J. Trott, and B. K. Vonderhaar (2002). Establishing a framework for the functional mammary gland: From endocrinology to morphology. J.Mammary Gland Biol.Neoplasia 7:17–38.

    PubMed  Google Scholar 

  2. 2.

    A. T. Cowie, I. A. Forsyth, and I. C. Hart (1980). Hormonalcontrol of lactation. Monogr.Endocrinol. 1–275.

  3. 3.

    Y. J. Topper and C. S. Freeman (1980). Multiple hormone interactions in the developmental biology of the mammary gland. Physiol.Rev.60:1049–1106.

    PubMed  Google Scholar 

  4. 4.

    J. A. Mol, I. Lantinga-van Leeuwen, E. van Garderen, and A. Rijnberk (2000). Progestin-induced mammary growth hormone(GH) production. Adv.Exp.Med.Biol.480:71–76.

    PubMed  Google Scholar 

  5. 5.

    K. Lippuner, H. J. Zehnder, J. P. Casez, R. Takkinen, and P. Jaeger (1996). PTH-related protein is released intothe mother's bloodstream during lactation: Evidence for beneficial effects on maternal calcium-phosphate metabolism. J.Bone Miner.Res.11:1394–1399.

    PubMed  Google Scholar 

  6. 6.

    B. Woodside, A. Abizaid, and C. Walker (2000). Changes in leptin levels during lactation: Implications for lactational hyperphagia and anovulation. Horm.Behav.37:353–365.

    PubMed  Google Scholar 

  7. 7.

    C. V. Clevenger and T. L. Plank (1997). Prolactin as an au-tocrine/paracrine factor in breast tissue. J.Mammary GlandBiol.Neoplasia 2:59–68.

    Google Scholar 

  8. 8.

    P. Ramamoorthy, R. Sticca, T. E. Wagner, and W. Y. Chen(2001). In vitro studies of a prolactin antagonist, hPRL-G129Rin human breast cancer cells. Int.J.Oncol.18:25–32.

    PubMed  Google Scholar 

  9. 9.

    B. K. Vonderhaar (1999). Prolactin involvement in breastcancer. Endocr.Relat.Cancer 6:389–404.

    PubMed  Google Scholar 

  10. 10.

    J. L. Kelsey and M. D. Gammon (1990). Epidemiology ofbreast cancer. Epidemiol.Rev.12:228–249.

    PubMed  Google Scholar 

  11. 11.

    D. Medina and G. H. Smith (1999). Chemical carcinogen-induced tumorigenesis in parous, involuted mouse mammary glands. J.Natl.Cancer Inst.91:967–969.

    PubMed  Google Scholar 

  12. 12.

    G. Thordarson, K. Van Horn, R. C. Guzman, S. Nandi, and F. Talamantes (2001). Parous rats regain high susceptibility to chemically induced mammary cancer after treatment with various mammotropic hormones. Carcinogenesis 22:1027–1033.

    PubMed  Google Scholar 

  13. 13.

    L. Sivaraman, S. G. Hilsenbeck, L. Zhong, J. Gay, O. M. Conneely, D. Medina, and B. W. O'Malley (2001). Early exposure of the rat mammary gland to estrogen and progesterone blocks co-localization of estrogen receptor expression and proliferation. J.Endocrinol.171:75–83.

    PubMed  Google Scholar 

  14. 14.

    C. Brisken (2002). Hormonal control of alveolar development and its implications for breast carcinogenesis. J.MammaryGland Biol.Neoplasia 7:49–66.

    Google Scholar 

  15. 15.

    P. E. Hartmann (1973). Changes in the composition and yield of the mammary secretion of cows during the initiation of lactation. J.Endocr.59:231–247.

    PubMed  Google Scholar 

  16. 16.

    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 

  17. 17.

    R. H. Martin, M.R. Glass, C. Chapman, G. D. Wilson, and K. L. Woods (1980). Human alpha-lactalbumin and hormonal factorsin pregnancy and lactation. Clin.Endocrinol.13:223–230.

    Google Scholar 

  18. 18.

    M. C. Neville, J. Morton, and S. Umemora (2001). Lactogenesis: The transition from pregnancy to lactation. Pediatr.Clin.North Am.48:35–52.

    PubMed  Google Scholar 

  19. 19.

    H. H. Traurig (1967). Cell proliferation in the mammary gland during late pregnancy and lactation. Anat.Rec.157:489–504.

    Google Scholar 

  20. 20.

    N. Normanno and F. Ciardiello (1997). EGF-related peptidesin the pathophysiology of the mammary gland. J.MammaryGland Biol.Neoplasia 2:143–151.

    Google Scholar 

  21. 21.

    K. L. Troyer and D. C. Lee (2001). Regulation of mouse mammary gland development and tumorigenesis by the ERBB signaling network. J.Mammary Gland Biol.Neoplasia 6:7–21.

    PubMed  Google Scholar 

  22. 22.

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

    PubMed  Google Scholar 

  23. 23.

    J. W. Pollard (2001). Tumour-stromal interactions: Transforming growth factor-beta isoforms and hepatocyte growthfactor/scatter factor in mammary gland ductal morphogenesis. Breast Cancer Res.3:230–237.

    PubMed  Google Scholar 

  24. 24.

    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 mammaryglands. J.Mammary Gland Biol.Neoplasia 5:31–42.

    PubMed  Google Scholar 

  25. 25.

    T. B. McFadden, R. M. Akers, and G. W. Kazmer (1987). Alpha-lactalbumin in bovine serum: Relationships with ud-derdevelopment and function. J.Dairy Sci.70:259–264.

    PubMed  Google Scholar 

  26. 26.

    B. K. Vonderhaar and S. E. Ziska (1989). Hormonal regulationof milk protein gene expression. Ann.Rev.Physiol.51:641–652.

    Google Scholar 

  27. 27.

    R. P. Deis and C. Delouis (1983). Lactogenesis induced byovariectomy in pregnant rats and its regulation by oestrogenand progesterone. J.Steroid Biochem.18:687–690.

    PubMed  Google Scholar 

  28. 28.

    Y. Mizoguchi, J. Y. Kim, T. Sasaki, T. Hama, M. Sasaki, J. Enami, and S. Sakai (1996). Acute expression of the PRLreceptor gene after ovariectomy in midpregnant mouse mam-marygland. Endocrine.J.43:537–544.

    Google Scholar 

  29. 29.

    Y. Mizoguchi, H. Yamaguchi, F. Aoki, J. Enami, and S. Sakai(1997). Corticosterone is required for the prolactin receptorgene expression in the late pregnant mouse mammary gland. Mol.Cell Endocrinol.132:177–183.

    PubMed  Google Scholar 

  30. 30.

    S. Nishikawa, R. C. Moore, N. Nonomura, and T. Oka (1994). Progesterone and EGF inhibit mouse mammary gland pro-lactinreceptor and ¯-casein gene expression. Am.J.Physiol.267:C1467–C1472.

    PubMed  Google Scholar 

  31. 31.

    D. D. Nguyen, A. F. Parlow, and M. C. Neville (2001). Hor-monalregulation of tight junction closure in the mouse mam-maryepithelium during the transition from pregnancy to lactation. J.Endocrinol.170:347–356.

    PubMed  Google Scholar 

  32. 32.

    M. E. Freeman, B. Kanyicska, A. Lerant, and G. Nagy (2000). Prolactin: Structure, function and regulation of secretion. Physiol.Rev.80:1523–1631.

    PubMed  Google Scholar 

  33. 33.

    Z. B. Andrews, I. C. Kokay, and D. R. Grattan (2001). Dissociation of prolactin secretion from tuberoinfundibulardopamine activity in late pregnant rats. Endocrinology 142:2719–2724.

    PubMed  Google Scholar 

  34. 34.

    D. J. Mellor, D. J. Flint, R. G. Vernon, and I. A. Forsyth (1987). Relationships between plasma hormone concentrations, udder development and the production of early mammary secretions in twin-bearing ewes on different planes of nutrition. Quart.J.Exp.Physiol.72:345–356.

    Google Scholar 

  35. 35.

    R. De Hertogh, K. Thomas, Y. Bietlot, I. Vanderheyden, and J. Ferin (1975). Plasma levels of unconjugated estrone, estra-dioland estriol and of HCS throughout pregnancy in normalwomen. J.Clin.Endocrinol.Metab.40:93–101.

    PubMed  Google Scholar 

  36. 36.

    D. Tulchinsky, C. J. Hobel, E. Yeager, and J. R. Marshall(1972). Plasma estrone, estradiol, progesterone and 17-hydroxyprogesterone in human pregnancy. 1. Normal pregnancy. Am.J.Obstet.Gynecol.112:1095–1100.

    PubMed  Google Scholar 

  37. 37.

    L. A. Rigg, A. Lein, and S. S. Yen (1977). Pattern of increasein circulating prolactin levels during human gestation. Am.J.Obstet.Gynecol.129:454–456.

    PubMed  Google Scholar 

  38. 38.

    B. R. Carr, C. R. Parker Jr., J. D. Madden, P. C. MacDonald, and J. C. Porter (1981). Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. Am.J.Obstet.Gynecol.139:416–422.

    PubMed  Google Scholar 

  39. 39.

    M. C. Neville (1983). Regulation of mammary developmentand lactation. In M. C. Neville and M. R. Neifert (eds.), Lactation: Physiology, Nutrition and Breast-feeding, PlenumPress, New York, pp. 103–140.

    Google Scholar 

  40. 40.

    R. H. Martin and R. E. Oakey (1982). The role of antena-taloestrogen in post-partum human lactogenesis: Evidencefrom oestrogen-deficient pregnancies. Clin.Endocrinol.17:403–408.

    Google Scholar 

  41. 41.

    J. K. Kulski, P. E. Hartmann, J. D. Martin, and M. Smith(1978). Effects of bromocriptine mesylate on the composi-tionof the mammary secretion in non-breast-feeding women. Obstet.Gynecol.52:38–42.

    PubMed  Google Scholar 

  42. 42.

    I. A. Forsyth and P. D. Lee (1993). Bromocriptine treatment ofperiparturient goats: Long-term suppression of prolactin andlack of effect on lactation. J.Dairy Res.60:307–317.

    PubMed  Google Scholar 

  43. 43.

    D. Schams (1972). Prolactin levels in bovine blood, influenced by milking manipulation, genital stimulation and oxytocin administration with specific consideration of the seasonal variations. Acta Endocrinol.71:684–696.

    PubMed  Google Scholar 

  44. 44.

    C. C. K. Tay, A. F. Glasier, and A. S. McNeilly (1996). Twentyfour hour patterns of prolactin secretion during lactation andthe relationship to suckling and the resumption of fertility in breast-feeding women. Hum.Reprod.11:950–955.

    PubMed  Google Scholar 

  45. 45.

    D. J. Flint and R. G. Vernon (1998). Effects of food restric-tionon the responses of the mammary gland and adiposetissue to prolactin and growth hormone in the lactating rat. J.Endocrinol.156:299–305.

    PubMed  Google Scholar 

  46. 46.

    L. J. Benedek-Jaszmann and V. Sternthal (1976). Late suppres-sionof lactation with bromocryptine. Practitioner 216:450.

    PubMed  Google Scholar 

  47. 47.

    H. Nagasawa and R. Yanai (1978). Mammary gland pro-lactinreceptor and pituitary prolactin secretion in lactatingmice with different lactational performance. Acta Endocrinol.88:94–98.

    PubMed  Google Scholar 

  48. 48.

    D. J. Flint and C. H. Knight (1997). Interactions of prolactinand growth hormone in the regulation of mamary gland function and epithelial cell survival. J.Mammary Gland Biol.Neoplasia 2:41–48.

    PubMed  Google Scholar 

  49. 49.

    K. L. Schwertfeger, M. M. Richer, and S. M. Anderson (2001). Mammary gland involution is delayed by activated Akt intransgenic mice. Mol.Endocrinol.15:867–881.

    PubMed  Google Scholar 

  50. 50.

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

    PubMed  Google Scholar 

  51. 51.

    S. Cassy, M. Charlier, L. Belair, M. Guillomot, G. Charron, B. Bloch, and J. Djiane (1998). Developmental expression andlocalization of the prolactin receptor (PRL-R) gene in ewemammary gland during pregnancy and lactation: Estimationof the ratio of the two forms of PRL-R messenger ribonucleicacid. Biol.Reprod.58:1290–1296.

    PubMed  Google Scholar 

  52. 52.

    Z. Z. Hu, J. Meng, and M. L. Dufau (2001). Isolation andcharacterization of two novel forms of the human prolactinreceptor generated by alternative splicing of a newly identifiedexon 11. J.Biol.Chem.276:41086–41094.

    PubMed  Google Scholar 

  53. 53.

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

    PubMed  Google Scholar 

  54. 54.

    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 epi-dermalgrowth factor activate Stat5 in different compartmentsof mammary tissue and exert different and overlapping developmental effects. Dev.Biol.229:163–175.

    PubMed  Google Scholar 

  55. 55.

    X. Liu, G. W. Robinson, K. U. Wagner, L. Garrett, A. Wynshaw-Boris, and L. Hennighausen (1997). Stat5a ismandatory for adult mammary gland development and lactogenesis. Genes Devel.11:179–186.

    PubMed  Google Scholar 

  56. 56.

    M. N. Emane, C. Delouis, P. A. Kelly, and J. Djiane (1986). Evolution of prolactin and placental lactogen receptorsin ewes during pregnancy and lactation. Endocrinology 118:695–700.

    PubMed  Google Scholar 

  57. 57.

    I. A. Forsyth (1994). Comparative aspects of placental lactogens: Structure and function. Exp.Clin.Endocrinol.102:244–251.

    PubMed  Google Scholar 

  58. 58.

    F. Talamantes and L. Ogren (1988). The placenta as an en-docrineorgan: Polypeptides. In E. Knobil and J. D. Neill (eds.),The Physiology of Reproduction, Raven Press, New York, pp. 2093–2144.

    Google Scholar 

  59. 59.

    P. Gaede, D. Trolle, and H. Pedersen (1978). Extremely lowplacental lactogen hormone (hPL) values in an otherwise un-eventlfulpregnancy preceding delivery of a normal baby. ActaObstet.Gynecol.Scand.57:203–209.

    Google Scholar 

  60. 60.

    P. V. Nielson, H. Pederson, and E. Kampmann (1979). Ab-senceof placental lactogen in an otherwise uneventful pregnancy. Am.J.Obstet.Gynecol.135:322–330.

    PubMed  Google Scholar 

  61. 61.

    A. Herman, C. Bignon, N. Daniel, J. Grosclaude, A. Gertler,and J. Djiane (2000). Functional heterodimerization of pro-lactinand growth hormone receptors by ovine placental lactogen. J.Biol.Chem.275:6295–6301.

    PubMed  Google Scholar 

  62. 62.

    R. W. Caron, G. A. Jahn, and R. P. Deis (1994). Lactogenicactions of different growth hormone preparations in pregnant and lactating rats. J.Endocrinol.142:535–545.

    PubMed  Google Scholar 

  63. 63.

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

    PubMed  Google Scholar 

  64. 64.

    E. L. Gregoraszczuk, T. Milewicz, J. Kolodziejczyk, J. Krzysiek, A. Basta, K. Sztefko, S. Kurek, and J. Stachura(2001). Progesterone-induced secretion of growth hormone, insulin-like growth factor I and prolactin by human breastcancer explants. Gynecol.Endocrinol.15:251–258.

    PubMed  Google Scholar 

  65. 65.

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

    PubMed  Google Scholar 

  66. 66.

    D. L. Rimoin, G. B. Holzman, T. J. Merimee, D. Rabinowitz, A. C. Barnes, J. E. Tyson, and V. A. McKusick (1968). Lac-tationin the absence of human growth hormone. J.Clin.Endocrinol.Metab.28:1183–1188.

    PubMed  Google Scholar 

  67. 67.

    A. L. Rosenbloom, J. Guevara-Aguirre, R. G. Rosenfeld, and U. Francke (1999). Growth hormone receptor deficiency in Ecuador. J.Clin.Endo.Metab.84:4436–4443.

    Google Scholar 

  68. 68.

    D. E. Bauman and R. G. Vernon (1993). Effects of exoge-nousbovine somatotropin on lactation. Annu.Rev.Nutr.13:437–461.

    PubMed  Google Scholar 

  69. 69.

    D. J. Flint and M. Gardner (1994). Evidence that growthhormone stimulates milk synthesis by direct action on themammary gland and that prolactin exerts effects on milk se-cretionby maintenance of mammary deoxyribonucleic acidcontent and tight junction status. Endocrinology 135:1119–1124.

    PubMed  Google Scholar 

  70. 70.

    K. M. Darcy, S. F. Shoemaker, P.-P. H. Lee, B. A. Ganis, and M. M. Ip (1995). Hydrocortisone and progesterone regulation of the proliferation, morphogenesis, and functional differentiation of normal rat mammary epithelial cells in three dimensional primary culture. J.Cell.Physiol.163:365–379.

    PubMed  Google Scholar 

  71. 71.

    S. Z. Haslam and G. Shyamala (1980). Progesterone receptorsin normal mammary gland: Receptor modulations in relation to differentiation. J.Cell Biol.86:730–737.

    PubMed  Google Scholar 

  72. 72.

    M. C. Neville and C. T. Walsh (1996). Effects of drugs on milk secretion and composition. In P. N. Bennett (ed.), Drugs andHuman Lactation, Elsevier, Amsterdam, pp. 15–45.

    Google Scholar 

  73. 73.

    F. Athie, K. C. Bachman, H. H. Head, M. J. Hayen, and C. J. Wilcox (1996). Estrogen administered at final milk removalaccelerates involution of bovine mammary gland. J.Dairy Sci.79:220–226.

    PubMed  Google Scholar 

  74. 74.

    H. S. Jin, S. Umemora, T. Iwasaka, and R. Y. Osamura (2000). Alterations of myoepithelial cells in the rat mammary glandduring pregnancy, lactation and involution, and after estradioltreatment. Pathol.Int.50:384–391.

    PubMed  Google Scholar 

  75. 75.

    Z. Feng, A. Marti, B. Jehn, H. J. Altermatt, G. Chicaiza, and R. Jaggi (1995). Glucocorticoid and progesterone inhibit in-volutionand programmed cell death in the mouse mammarygland. J.Cell Biol.131:1095–1103.

    PubMed  Google Scholar 

  76. 76.

    N. F. Butte, J. M. Hopkinson, J. K. Moon, N. Mehta, and E. O. Smith (1999). Adjustments in energy expenditure andsubstrate utilization during late pregnancy and lactation. Am.J.Clin.Nutr.69:299–307.

    PubMed  Google Scholar 

  77. 77.

    K. L. Blaxter, E. P. Reineke, E. S. Crampton, and W. E. Petersen (1949). The role of thyroidal materials and of syn-theticgoitrogens in animal production and an appraisal of their practical use. J.Anim.Sci.8:307–352.

    Google Scholar 

  78. 78.

    A. V. Capuco, S. Kahl, L. J. Jack, J. O. Bishop, and H. Wallace(1999). Prolactin and growth hormone stimulation of lactationin mice requires thyroid hormones. Proc.Soc.Exp.Biol.Med.221:345–351.

    PubMed  Google Scholar 

  79. 79.

    S. E. Ziska, M. Bhattacharjee, R. L. Herber, P. K. Qasba, and B. K. Vonderhaar (1988). Thyroid hormone regulation ofalpha-lactalbumin: Differential glycosylation and messengerribonucleic acid synthesis in mouse mammary glands. Endocrinology 123:2242–2248.

    PubMed  Google Scholar 

  80. 80.

    Y. Iwatani, N. Amino, O. Tanizawa, H. Mori, M. Kawashima,Y. Yabu, and K. Miyai (1987). Decrease of free thyroxin inserum of lactating women. Clin.Chem.33:1217–1219.

    PubMed  Google Scholar 

  81. 81.

    G. A. van Haasteren, H. van Toor, W. Klootwijk, B. Handler,E. Linkels, P. van der Schoot, J. van Ophemert, F. H. DeJong,T. J. Visser, and W. J. de Greef (1996). Studies on the role ofTRHand corticosterone in the regulation of prolactin and thy-rotrophinsecretion during lactation. J.Endocrinol.148:325–336.

    PubMed  Google Scholar 

  82. 82.

    L. J. Jack, S. Kahl, D. L. St Germain, and A. V. Capuco (1994). Tissue distribution and regulation of 50-deiodinase processesin lactating rats. J.Endocrinol.142:205–215.

    PubMed  Google Scholar 

  83. 83.

    L. Navarro, A. Landa, C. Valverde-R, and C. Aceves (1999). Mammary gland type I iodthyronine deiodinase is encoded bya short messenger ribonucleic acid. Endocrinology 138:4248–4254.

    Google Scholar 

  84. 84.

    L. Quevedo-Corona, M. Franco-Colin, M. Caudillo-Romero,J. Pacheco-Rosado, S. Zamudio-Hernandez, and R. Racotta(2000). 3,5,30-Triiodothyronine administered to rat dams dur-inglactation increases milk yield and triglyceride concentra-tionand hastens pups growth. Life Sci.66:2013–2121.

    PubMed  Google Scholar 

  85. 85.

    S. R. Davis, R. J. Collier, J. P. McManamara, H. H. Head,and W. Sussman (1988). Effects of thyroxine and growth hor-monetreatment of dairy cows on milk yield, cardiac outputand mammary blood flow. J.Anim.Sci.66:70–79.

    PubMed  Google Scholar 

  86. 86.

    F. Peters, J. Schulze-Tollert, and W. Schuth (1991). Thyrotrophin-releasing hormone—A lactation-promotingagent? Br.J.Obstet.Gynecol.98:880–885.

    Google Scholar 

  87. 87.

    S. Y. Kyriakou and N. J. Kuhn (1973). Lactogenesis in the diabetic rat. J.Endocrinol.59:199–200.

    PubMed  Google Scholar 

  88. 88.

    K. Hove (1978). Maintenance of lactose secretion during acute insulin deficiency in lactating goats. Acta Physiol.Scand.103:173–179.

    PubMed  Google Scholar 

  89. 89.

    M. C. Neville and M. F. Picciano (1997). Regulation of milklipid synthesis and composition. Ann.Rev.Nutr.17:159–184.

    Google Scholar 

  90. 90.

    R. A. DeFronzo, J. D. Tobin, and R. Andres (1979). The glu-coseclamp technique. Amethod for quantifying insulin secre-tionand resistance. Am.J.Physiol.237:E214–E223.

    PubMed  Google Scholar 

  91. 91.

    J. M. Griinari, M. A. McGuire, D. A. Dwyer, D. E. Bauman, D. M. Barbano, and W. E. House (1997). The role of insulin inthe regulation of milk protein synthesis in dairy cows. J.DairySci.80:2361–2371.

    Google Scholar 

  92. 92.

    M. C. Neville, V. Sawicki, and W. W. Hay Jr. (1993). Effect offasting, elevated plasma glucose and plasma insulin concentration son milk secretion in women. J.Endocrinol.139:165–173.

    PubMed  Google Scholar 

  93. 93.

    W. R. Crowley and W. E. Armstrong (1992). Neurochemi-calregulation of oxytocin secretion in lactation. Endocr.Rev.13:33–65.

    PubMed  Google Scholar 

  94. 94.

    W. S. Young III, E. Shepard, J. Amico, L. Hennighausen, K. U. Wagner, M. E. LaMarca, C. McKinney, and E. I. Ginns (1996). Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition. J.Neuroendocrinol.8:847–853.

    PubMed  Google Scholar 

  95. 95.

    G. Gimpl and F. Fahrenholz (2001). The oxytocin receptor system: Structure, function and regulation. Physiol.Rev 81:629–683.

    PubMed  Google Scholar 

  96. 96.

    R. M.Akers and A. M.Lefcourt (1982). Milking-and suckling-inducedsecretion of oxytocin and prolactin in parturient dairycows. Horm.Behav.16:87–93.

    PubMed  Google Scholar 

  97. 97.

    A. S. McNeilly, I. C. Robinson, M. J. Houston, and P. W. Howie(1983). Release of oxytocin and prolactin in response to suck-ling. Br.Med.J.Clin.Res.286:257–259.

    Google Scholar 

  98. 98.

    M. S. Soloff, M. Alexandrova, and M. J. Fernstrom (1979). Oxytocin receptors: Triggers for parturition and lactation? Science 204:1313–1315.

    PubMed  Google Scholar 

  99. 99.

    A. Sapino, L. Macri, L. Tonda, and G. Bussolati (1993). Oxy-tocinenhances myoepithelial cell differentiation and prolifer-ationin the mouse mammary gland. Endocrinology 133:838–842.

    PubMed  Google Scholar 

  100. 100.

    J. A. Amico, A. Thomas, R. S. Crowley, and L. A. Burmeister(1998). Concentrations of leptin in the serum of pregnant,lactating, and cycling rats and of leptin messenger ribonucleicacid in rat placental tissue. Life Sci.63:1387–1395.

    PubMed  Google Scholar 

  101. 101.

    H. J. Kalkwarf (1999). Hormonal and dietary regulation of changes in bone density during lactation and after weaning in women. J.Mammary Gland Biol.Neoplasia 4:319–329.

    PubMed  Google Scholar 

  102. 102.

    P. Martyn and I. A. Hansen (1981). Initiation of lipogenic en-zymeactivities in rat mammary glands. Biochem.J.198:187–192.

    PubMed  Google Scholar 

  103. 103.

    R. W. Mellenberger and D. E. Bauman (1974). Metabolicadaptations during lactogenesis: Fatty acid synthesis in rab-bitmammary tissue during pregnancy and lactation. Biochem.J 138:373–379.

    PubMed  Google Scholar 

  104. 104.

    M. Peaker and C. J. Wilde (1996). Feedback control of milksecretion from milk. J.Mammary Gland Biol.Neoplasia 1:307–315.

    PubMed  Google Scholar 

  105. 105.

    R. D. Burgoyne and C. J. Wilde (1994). Control of secre-toryfunction in mammary epithelial cells. Cell.Signal.6:607–616.

    PubMed  Google Scholar 

  106. 106.

    K. A. Hammond, K. C. Lloyd, and J. Diamond (1996). Is mam-maryoutput capacity limiting to lactational performance inmice. J.Exp.Biol.199:337–349.

    PubMed  Google Scholar 

  107. 107.

    A. W. Bell and D. E. Bauman (1997). Adaptations of glu-cosemetabolism during pregnancy and lactation. J.MammaryGland Biol.Neoplasia 2:265–278.

    Google Scholar 

  108. 108.

    M. C. Neville (1995). Volume and caloric density of human milk. In R. G. Jensen (ed.), Handbook of Milk Composition, Academic Press, San Diego, pp. 101–113.

    Google Scholar 

  109. 109.

    C. J. Wilde, C. H. Knight, and D. J. Flint (1999). Controlof milk secretion and apoptosis during mammary involution. J.Mammary Gland Biol.Neoplasia 4:129–136.

    PubMed  Google Scholar 

  110. 110.

    A. Marti, Z. W. Feng, H. J. Altermatt, and R. Jaggi (1997). Milk accumulation triggers apoptosis of mammary epithelialcells. Eur.J.Cell Biol.73:158–165.

    PubMed  Google Scholar 

  111. 111.

    E. Tonner, G. J. Allan, and D. J. Flint (2000). Hormonal controlof plasmin and tissue-type plasminogen activator activity in ratmilk during involution of the mammary gland. J.Endocrinol.167:265–273.

    PubMed  Google Scholar 

  112. 112.

    I. H. Russo, M. Koszalka, and J. Russo (1990). Humanchorionic gonadotropin and rat mammary cancer prevention. J.Natl.Cancer Inst.82:1286–1289.

    PubMed  Google Scholar 

  113. 113.

    L. Sivaraman, O. M. Conneely, D. Medina, and B. W. O'Malley(2001). p53 is a potential mediator of pregnancy and hormone-inducedresistance to mammary carcinogenesis. Proc.Natl.Acad.Sci.U.S.A.98:12379–12384.

    PubMed  Google Scholar 

  114. 114.

    H. P. Gardner, S. I. Ha, C. Reynolds, and L. A. Chodosh (2000). The caM kinase, Pnck, is spatially and temporally regulatedduring murine mammary gland development and may identify an epithelial cell subtype involved in breast cancer. Cancer Res.60:5571–5577.

    PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Neville, M.C., McFadden, T.B. & Forsyth, I. Hormonal Regulation of Mammary Differentiation and Milk Secretion. J Mammary Gland Biol Neoplasia 7, 49–66 (2002). https://doi.org/10.1023/A:1015770423167

Download citation

  • lactogenesis
  • endocrine regulation
  • prolactin
  • placental lactogen
  • progesterone
  • breast cancer risk