Skip to main content
SpringerLink
Log in

Mammary Gland

  • Chapter
Estrogens and Antiestrogens II

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 135 / 2))

  • 684 Accesses

Abstract

Estrogen is a growth hormone in target tissues such as breast, endometrium, vagina and bone, and has major effects on liver function. It has long been known from experimental studies that estrogen is important for the development and growth of the breast during fetal life, puberty and pregnancy. However, estrogen alone cannot exert a full effect on breast cell growth. In different animal models and in in vitro breast cell cultures, estrogen stimulates ductal development, while progesterone is necessary for the development of acini cells in the alveoli. Neither estrogen nor progesterone alone or in combination is sufficient for normal proliferation and differentiation of the mammary gland. This requires a number of other hormones, such as insulin, cortisol, thyroxin, prolactin and growth hormone (GH) (Russo et al. 1990; DICKSON and LIPPMAN 1995). However, basic knowledge of the effects of estrogen and progestogen on normal breast epithelium and on the regulation of proliferation is still lacking. Estrogen is generally accepted as a promoter of breast epithelial cells both in vitro and in vivo and is also involved in the development and growth of breast cancer (COLDITZ et al. 1993; PIKE et al. 1993). However, there is not yet full consensus regarding the effects of progesterone/ progestogens alone or in combination with estrogen on the breast. All over the world, women have made highly justified demands for information about exogenous hormonal treatment and individual risk assessments.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Anderson TJ, Ferguson DJ, Raab GM(1982)Cell turnover in the “resting” human breast: influence of parity, contraceptive pill, age and laterality. Br J Cancer 46:376–382

    Article  PubMed  CAS  Google Scholar 

  • Anderson TJ, Battersby S, King RJB, McPherson K., Going 11(1989)Oral contraceptive use influences breast cell proliferation. Hum PathoI20:1139–1141

    Article  Google Scholar 

  • Aronica SM, Katzenellenbogen BS(1993)Stimulation of estrogen receptor mediated transcription and alteration in the phosphorylation state of the rat uterine estrogen receptor by estrogen, cyclic adenosine monophosphate and insulin-like growth factor-I. Mol Endocrinol 7:743–752

    Article  PubMed  CAS  Google Scholar 

  • Badwe RA, Gregory WM, Chaudary MA, Richards MA, Bentley AE, Rubens RD, Fentiman IS(1991)Timing of surgery during menstrual cycle and survival of premenopausal women with operable breast cancer. Lancet 337:1261–1264

    Article  PubMed  CAS  Google Scholar 

  • Bates SE, Davidson NE, Valverius EM, Freter CE, Dickson RB, Tam JP, Kudlow JE, Lippman ME, Salomon DS(1988)Expression of transforming growth factor alpha and its mRNA in human breast cancer: its regulation by estrogen and its possible functional significance. Mol Endocrinol 2:543–555

    Article  PubMed  CAS  Google Scholar 

  • Battersby S, Robertson BJ, Anderson TJ, King RJB, McPherson K(1992)Influence of menstrual cycle, parity and oral contraceptive use on steroid hormone receptors in normal breast. Br J Cancer 65:601–607

    Article  PubMed  CAS  Google Scholar 

  • Butterworth BE, Goldsworthy TL(1991)The role of cell proliferation in multistage carcinogenesis. Proc Soc Exp Bioi Med 198:683–687

    CAS  Google Scholar 

  • Carlstrom K(1984)Influence of intratumoural estradiol biosynthesis on estrogen receptors. Recent Results Cancer Res 91:145–149

    Article  PubMed  CAS  Google Scholar 

  • Chang KJ, Lee TTY, Linares-Cruz G, Fournier S, de Lignieres B(1995)Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril 63:785–791

    PubMed  CAS  Google Scholar 

  • Clarke CL, Sutherland RL(1990)Progestin regulation of cellular proliferation. Endocr Rev 11:266–-301

    Article  PubMed  CAS  Google Scholar 

  • Cline JM, SOderqvist G, von Schoultz E, Skoog L, von Schoultz B(1996)Effects of hormone replacement therapy on the mammary gland of surgically postmenopausal macaques. Am J Obstet GynecoI174:93–100

    Article  Google Scholar 

  • Cohen SM, Purtilo DT, Ellwein LB(1991)Pivotal role of increased cell proliferation in human carcinogenesis. Mod PathoI4:371–382

    Google Scholar 

  • Colditz GA, Egan KM, Stampfer MJ(1993)Hormone replacement therapy and risk of breast cancer: results from epidemiologic studies. Am J Obstet Gynecol 168:1473–1480

    PubMed  CAS  Google Scholar 

  • Colditz GA, Hankinson SE, Hunter DJ, Willett WC, Manson JE, Stampfer MJ, Hennekens C, Rosner B, Speizer FE(1995)The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 332:1589-1593

    Google Scholar 

  • Collaborative Group on Hormonal Factors in Breast Cancer(1997)Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52705 women with breast cancer and 108411 women without breast cancer. Lancet 350:1047–1059

    Google Scholar 

  • de Boever J, Verheugen C, Van Maele G, Vandekerckhove D (1983)Steroid concentrations in serum, glandular breast tissue, and breast cyst fluid of control and progesterone treated patients. In: Angeli A (ed) Endocrinology of cystic breast disease. Raven Press, New York, pp 93–99

    Google Scholar 

  • Dickson RB, Lippman ME(1995)Growth factors in breast cancer. Endocr Rev 16:559–589

    PubMed  CAS  Google Scholar 

  • Dickson RB, Huff KK, Spencer EM, Lippman ME(1986)Induction of epidermal growth factor-related polypeptides by 17f3-estradiol in MCF-7 human breast cancer cells. Endocrinology 118:138–142

    Article  PubMed  CAS  Google Scholar 

  • DuPont WD, Page DL(1985)Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 312:146–151

    Article  PubMed  CAS  Google Scholar 

  • Eriksen EF(1986)Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease. Endocr Rev 7:379–408

    Article  PubMed  CAS  Google Scholar 

  • Evan G (1995)The integrated control of cell proliferation and programmed cell death (apoptosis) by oncogenes (abstract). International symposium on the molecular biology of breast cancer, Lillehammer, Norway

    Google Scholar 

  • Gambrell RD (1988)Studies of endometrial and breast disease with hormone replacement therapy. In: Studd JWW, Whitehead MI (eds) The menopause. Blackwell, Oxford, England, pp 247–261Goldfine

    Google Scholar 

  • ID, Papa V, Vigneri R, Siiteri P, Rosenthal S(1992)Progestin regulation of insulin and insulin-like growth factor 1 receptors in cultured human breast cancer cells. Breast Cancer Res Treat 22:69–79

    Article  PubMed  CAS  Google Scholar 

  • Gompel A, Malet C, Spritzer P, Lalardrie JP, Kuttenn F, Mauvais-Jarvis P(1986) Progestin effect on cell proliferation and 17 f3-hydroxysteroid dehydrogenase activity in normal human breast cells in culture. J Clin Endocrinol Metab 63:1174–1180

    Article  PubMed  CAS  Google Scholar 

  • Harris JR, Lippman ME, Morrow M, Hellman S (1996) Diseases of the breast. Lippincott-Raven, Philadelphia

    Google Scholar 

  • Hutchinson TA, Polansky SM, Feinstein AR(1979)Post-menopausal estrogens protect against fractures of hip and distal radius. A case-control study. Lancet 2:705–709

    CAS  Google Scholar 

  • Key TJ, Pike MC(1988)The dose-effect relationship between “unopposed” estrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk. Br J Cancer 57:205–212

    Article  PubMed  CAS  Google Scholar 

  • Kiel DP, Felson DT, Anderson JJ, Wilson PW, Moskowitz MA(1987)Hip fractures and the use of estrogens in postmenopausal women. N Engl J Med 317:1169–1174

    Article  PubMed  CAS  Google Scholar 

  • King RJB, Wang DY, Daley RJ, Darbre PD(1989)Approaches to studying the role of growth factors in the progression of breast tumors from the steroid sensitive to the insensitive state. J Steroid Biochem 34:133–138

    Article  PubMed  CAS  Google Scholar 

  • Knabbe C, Lippman ME, Wakefield LM, Flanders KC, Kasid A, Derynck R, Dickson RB(1987)Evidence that TGF f3is a hormonally regulated negative growth factor in human breast cancer. Cell 48:417–428

    Article  PubMed  CAS  Google Scholar 

  • Knabbe C, Zugmaier G, Schmahl M, Dietel M, Lippman ME, Dickson RB(1991)Induction of transforming growth factor beta by the antiestrogens droloxifen, tamoxifen, and toremifen in MCF-7 cells. Am J Clin OncoI14:S15-S20

    Article  Google Scholar 

  • Kyprianu N, English H, Davidson NE, Isaacs IT(1995)Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation. Cancer Res 51:162–166

    Google Scholar 

  • Laidlaw II, Clarke RB, Howell A, Owen AWMC, Potten CS, Anderson E(1995)The proliferation of normal human breast tissue implanted into athymic nude mice is stimulated by estrogen but not progesterone. Endocrinology 136:164–171

    Article  PubMed  CAS  Google Scholar 

  • Liu SC, Sanfilippo B, Perroteau I, Derynck R, Salomon DS, Kidwell WR(1987)Expression of transforming growth factor a (TGFa) in differentiated rat mammary tumors: estrogen induction of TGFa production. Mol EndocrinoI1:683–-692

    Article  Google Scholar 

  • London SJ, Connolly JL, Schnitt SJ, Colditz GA(1992)A prospective study of benign breast disease and the risk of breast cancer. JAMA 267:941–944

    Article  PubMed  CAS  Google Scholar 

  • Longacre TA, Bartow SA(1987)A correlative morphologic study of human breast and endometrium in the menstrual cycle. Am J Surg Pathol 10:382–393

    Google Scholar 

  • Maentausta 0, Sormunen R, Isomaa V, Lehto VP, Jouppila P, Vihko R(1991)Immunohistochemical localization of 17 f3-hydroxysteroid dehydrogenase in the human endometrium during the menstrual cycle. Lab Invest 65:582–587

    PubMed  CAS  Google Scholar 

  • Markopoulos C, Berger U, Wilson P, Gazet JC, Coombes RC(1988)Estrogen receptor content of normal breast cells and breast carcinomas throughout the menstrual cycle. BMJ 296:1349–1351

    Article  PubMed  CAS  Google Scholar 

  • Mauvais-Jarvis P, Kuttenn F, Gompel A(1986)Antiestrogen action of progesterone in breast tissue. Breast Cancer Res Treat 8:179–188

    Article  PubMed  CAS  Google Scholar 

  • Moolgavkar SH, Day NE, Stevens RG(1980)lWo-stage model of carcinogenesis: epidemiology of breast cancer in females. J Natl Cancer Inst 65:559–569

    PubMed  CAS  Google Scholar 

  • Murphy LC, Dotslaw H(1989)Regulation of transforming growth factor a messenger ribonuleic acid abundace in T47 D human breast cancer cells. Mol Endocrinol 3:611–-617

    Article  PubMed  CAS  Google Scholar 

  • Murphy LJ, Sutherland RL, Steed B, Murphy LC, Lazarus L(1986)Progestin regulation of epidermal growth factor receptor in human mammary carcinoma cells. Mol EndocrinoI46:728–734

    Google Scholar 

  • Murphy LC, Murphy LJ, Dubik D, Bell GI, Shiu RPC(1988)Epidermal growth factor gene expression in human breast cancer cells: regulation of expression by progestins. Cancer Res 48:4555–4560

    PubMed  CAS  Google Scholar 

  • Musgrove EA, Lee CSL, Sutherland RL(1991)Progestins both stimulate and inhibit breast cancer cell cycle progression while increasing expression of transforming growth factor a, epidermal growth factor receptor, c-fos, and c-myc genes. Mol Cell BioI 11:5032–5043

    CAS  Google Scholar 

  • Nathorst Boos J (1993) Hysterectomy, oophorectomy and estrogen replacement therapy. Thesis, Karolinska Institute, Stockholm, Sweden

    Google Scholar 

  • Paganini-Hill A, Chao A, Ross RK, Henderson BE(1991)Exercise and other factors in prevention of hip fracture: the Lesure World study. Epidemiology 2:16–25

    Article  PubMed  CAS  Google Scholar 

  • Page DL, DuPont WD, Rogers LW(1988)Ductal involvement by cells of atypical lobular hyperplasia in the breast: a long-term follow-up study of cancer risk. Hum PathoI19:201–207

    Article  Google Scholar 

  • Pike MC (1990)Hormonal contraception with LHRH agonists and the prevention of breast and ovarian cancer. In: Mann RD (ed) Oral contraceptives and breast cancer. Parthenon, Lancaster, England, pp323–348

    Google Scholar 

  • Pike MC, Spicer DV, Dahmoush L, Press MF(1993)Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 15:17–35

    PubMed  CAS  Google Scholar 

  • Pitot HC (1986) Fundamentals of oncology, 3rd edn. Marcel Dekker, New York

    Google Scholar 

  • Potten CS, Watson RJ, Williams GT, et al. (1988)The effect of age and menstrual cycle upon proliferative activity of the normal human breast. Br J Cancer 58:163–170

    Article  PubMed  CAS  Google Scholar 

  • Poutanen M, Isomaa V, Peltoketo H, Vihko R(1995)Regulation of estrogen action: role of 17 J3-hydroxysteroid dehydrogenases. Ann Med 27:675–682

    Article  PubMed  CAS  Google Scholar 

  • Reed MJ,Singh A, Ghilchik MW, Coldham NG, Purohit A (1991) Regulation of estradiol 17 J3-hydroxysteroid dehydrogenase in breast tissues: the role of growth factors. J Steroid Biochem Mol BioI 39:791–798

    Article  CAS  Google Scholar 

  • RussoJ, Russo IH (1995) Hormonally induced differentiation: a novel approach to breast cancer prevention. J Cell Biochem Suppl 22:58–64

    Article  PubMed  CAS  Google Scholar 

  • RussoJ, Gusterson BA, Rogers AE, Russo IH, Wellings SR, van Zwieten MJ (1990) Comparative study of human and rat mammary tumorigenesis. Lab Invest 62:244–278

    PubMed  CAS  Google Scholar 

  • SantnerSJ, Feil PD, Santen RJ (1985) In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway. J Clin Endocrinol Metab 53:29–33

    Google Scholar 

  • SenieRT, Rosen Pp, Rhodes P, Lesser ML (1995) Timing of breast cancer excision during the menstrual cycle influences duration of disease free survival. Ann Intern Med 115:337–342

    Google Scholar 

  • SoderqvistG, von SchoultzB, Skoog L, Tani E (1993) Estrogen and progesterone receptor content in breast epithelial cells from healthy women during the menstrual cycle. Am J Obstet Gynecol 168:874–879

    PubMed  CAS  Google Scholar 

  • Soderqvist G, Olsson H, Wilking N, von Schoultz B, Carlstrom K (1994) Metabolism of estrone sulfate by normal breast tissue: influence of menopausal status and oral contraceptives. J Steroid Biochem Mol BioI 48:221–224

    Article  Google Scholar 

  • SoderqvistG, Isaksson E, von Schoultz B, Carlstrom K, Tani E, Skoog L (1997) Proliferation of breast epithelial cells in healthy women during the menstrual cycle. Am J Obstet Gynecol176:123–128

    Article  PubMed  Google Scholar 

  • SoderqvistG, Poutanen M, Wickman M, von Schoultz B, Skoog L, Vihko R (1998) 17 J3-hydroxysteroid dehydrogenase type 1 in normal breast tissue during the menstrual cycle and hormonal contraception. J Clin Endocrinol Metab 83:1190–1193

    Article  PubMed  Google Scholar 

  • Stewart AJ, Johnson MD, May FEB, Westley BR (1990) Role of insulin-like growth factor and the type 1 insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells. J BioI Chern 265:21172–21178

    CAS  Google Scholar 

  • StreuliCH, Dive C, Hickman JA, Farrely N, Metcalfe A (1997) Control of apoptosis in breast epithelium. Endocrine-Related Cancer 4:45–53

    Article  CAS  Google Scholar 

  • SutherlandRL, Hamilton JA, Sweeney KJE, Watts CKW, Musgrove EA (1997) Expression and regulation of cyclin genes in breast cancer.Acta OncoI34:651–656

    Article  Google Scholar 

  • VeronesiU, Luini A, Mariani L, Del Vecchio M, Alvez D, Andreoli C, Giacobone A, Merson M, Pacetti G, Raselli R, et al. (1994) Effect of menstrual phase on surgical treatment of breast cancer. Lancet 343:1545–1547

    Article  PubMed  CAS  Google Scholar 

  • Vihko R, Isomaa V (1989)Endocrine aspects of endometrial cancer. In: Voigt KD, Knabbe C (eds) Endocrine dependent tumors. Raven, New York, pp 197–214

    Google Scholar 

  • VogelPM, Georgiade NG, Fetter BF, Vogel FS, McCarty KS lr (1981) The correlation of histologic changes in the human breast with the menstrual cycle. Am 1 Pathol 104:23–34

    CAS  Google Scholar 

  • WangTTY, Phang 1M (1995) Effects of estrogen on apoptotic pathways in human breast cancer cell line MCF-7. Cancer Res 55:2487–2489

    PubMed  CAS  Google Scholar 

  • Wu L, EinsteinM, GeisslerWM, Chan HK, EllistonKO, AnderssonS(1993)Expression cloning and characterization of human 17 f3-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20a-hydroxysteroid dehydrogenase activity. 1 BioI Chern 268:12964–12969

    CAS  Google Scholar 

Download references

Authors
  1. G. Söderqvist
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Von Schoultz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Söderqvist, G., Schoultz, B.V. (1999). Mammary Gland. In: Estrogens and Antiestrogens II. Handbook of Experimental Pharmacology, vol 135 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60107-1_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60107-1_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64261-6

  • Online ISBN: 978-3-642-60107-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation