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Oestrone sulphate, adipose tissue, and breast cancer

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Summary

Oestrone sulphate, the oestrogen in highest concentration in the plasma, may play a role in the induction and growth of breast cancers. By enzymolysis and radioimmunoassay, oestrone sulphate concentrations were measured in 3 biological fluids. High concentrations of the conjugate (up to 775 nmol/l) were detected in breast cyst fluids from some premenopausal women, the concentrations in blood plasma (0.91–4.45 nmol/l) being much lower. Concentrations in the plasmas from postmenopausal women with (0.23–4.63 nmol/l) or without (0.18–1.27 nmol/l) breast cancer were still lower. Oestrone sulphate concentration in cow's milk or cream (0.49–0.67 nmol/l) was also low: dietary intake in these fluids is probably of little consequence. The capacity of breast tissues for hydrolysis of oestrone sulphate was examined in two ways:

  1. 1.

    In tissue slices incubated with 85 pM (3H) oestrone sulphate solution at 37° C, cancers (131–412 fmol/g tissue/hr) and adipose tissues (23–132 fmol/g tissue/hr) hydrolysed significantly more sulphate than did benign tissues (1–36 fmol/g tissue/hr).

  2. 2.

    In tissue homogenates incubated with 5–25µM [3H] oestrone sulphate at 37° much higher capacities for hydrolysis (nmol/g tissue/hr) were demonstrated with a Km of 2–16.5µM: cancers (34–394) and benign tissues (9–485) had significantly higher sulphatase activities than adipose tissues (9–39). On a protein basis, however, the sulphatase activities in the 3 tissues were comparable. It is concluded that oestrone sulphate is present in breast cysts and blood plasma and thatin vitro, the conjugated hormone can be hydrolysed by breast tissues. The biological significance of these findingsin vivo remains to be established.

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References

  1. Korenman SG: The estrogen window hypothesis. Lancet i:700, 1980

    Google Scholar 

  2. Miller AB, Bulbrook RD: The epidemiology and etiology of breast cancer (special report Leeds Castle Meeting 19–22 June 1980). New Engl J Med 303:1246–1248, 1980

    PubMed  Google Scholar 

  3. MacMahon B, Cole P, Brown J: Etiology of human breast cancer: a review. J Natl Cancer Inst 50:21–42, 1973

    PubMed  Google Scholar 

  4. Carroll KK: Experimental evidence of dietary factors and hormone-dependent cancers. Cancer 35:3374–3383, 1975

    Google Scholar 

  5. Gaskill SP, McGuire WL, Osborne CK, Stern MP: Breast cancer mortality and diet in the United States. Cancer Res 39:3628–3637, 1979

    PubMed  Google Scholar 

  6. Purdy RH, Engel LL, Oncley JL: The characterisation of oestrone sulphate from human plasma. J Biol Chem 236:1043–1050, 1961

    PubMed  Google Scholar 

  7. Hawkins RA, Oakey RE: Estimation of oestrone sulphate, oestradiol-17β and oestrone in peripheral plasma: concentrations during the menstrual cycle and in man. J Endocrinol 60:1–17, 1974

    Google Scholar 

  8. Heap RB, Flint APF, Hartman PE, Gadsby JE, Staples LD, Ackland N, Hamon M: Oestrogen production in early pregnancy. J Endocrinol 89 (Suppl): 77–94, 1981

    Google Scholar 

  9. Bradlow HL, Rosenfeld RS, Kream J, Fleisher M, O'Connor J, Schwartz MK: Steroid hormone accumulation in human breast cyst fluid. Cancer Res 41:105–107, 1981

    PubMed  Google Scholar 

  10. Hoover R, Gray LA, Cole P, MacMahon B: Menopausal oestrogens and breast cancer. New Engl J Med 295:401–405, 1976

    PubMed  Google Scholar 

  11. Shutt DA, Cox RI: Steroid and phyto-oestrogen binding to sheep uterine receptors in vitro. J Endocrinol 52:299–310, 1972

    PubMed  Google Scholar 

  12. Hawkins RA: Studies on the oestrogens in peripheral plasma of the non-pregnant human. PhD Thesis, University of Leeds, 1975, p 60

  13. Sandberg EC, Jenkins RC: Hydrolysis of the sulfuric acid esters of steroid compounds. Methods in Enzymology 15:654–690, 1969

    Google Scholar 

  14. Dao TL, Hayes C, Libby PR: Steroid sulphatase activities in human breast tumours. Proc Soc Exp Biol Med 146:381–384, 1974

    PubMed  Google Scholar 

  15. Vignon F, Terqui M, Westley B, Derocq D, Rochefort H: Effects of plasma oestrogen sulphates in mammary cancer cells. Endocrinology 106:1079–1086, 1980

    PubMed  Google Scholar 

  16. Wilking N, Carlstrom K, Gustaffson SA, Skoldefors H, Tollbom O: Oestrogen receptors and metabolism of oestrone sulphate in human mammary carcinoma. Europ J Cancer 16:1339–1344, 1980

    Google Scholar 

  17. Santner SJ, Feil PD, Santen RJ: In situ estrogen production via the estrone sulfatase pathway in breast tumours: importance versus the aromatase pathway. J Clin Endocrinol Metab 59:29–33, 1984

    PubMed  Google Scholar 

  18. Kelch RP, Kaplan SL, Grumbach MM: Suppression of urinary and plasma follicle-stimulating hormone by exogenous oestrogens in pre-pubertal and pubertal children. J Clin Invest 52:1122–1128, 1973

    PubMed  Google Scholar 

  19. Miller WR, Roberts MM, Creel RJ, Yap PL, Kelly RW, Forrest APM: Androgen conjugates in human breast cyst fluids. J Natl Cancer Inst 69:1055–1058, 1982

    PubMed  Google Scholar 

  20. Iwamori M, Moser HW, Kishmoto Y: Solubilization and partial purification of steroid sulphatase from rat liver: characterisation of oestrone sulphatase. Arch Biochem Biophys 174:199–208, 1976

    PubMed  Google Scholar 

  21. Prost O, Turrel MD, Dahan N, Craveur C, Adessi GL: Estrone and dehydroepiandrosterone sulfatase activities and plasma estrone sulfate levels in human breast carcinoma. Cancer Res 44:661–664, 1984

    PubMed  Google Scholar 

  22. Tseng L, Mazella J, Lee LY, Stone ML: Estrogen sulfatase and estrogen sulfotransferase in human primary mammary carcinoma. J Steroid Biochem 19:1413–1417, 1983

    PubMed  Google Scholar 

  23. Hanes CS: Studies on plant amylases. 1. The effect of starch concentration upon the velocity of hydrolysis by the amylase of germinated barley. Biochem J 26:1406–1421, 1932

    Google Scholar 

  24. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analyt Biochem 72:248–254, 1976

    PubMed  Google Scholar 

  25. Raju U, Bradlow HL, Levitz M: Estriol in human breast cyst fluid. J Steroid Biochem 20:1061–1065, 1984

    PubMed  Google Scholar 

  26. Towobola OA, Crilly RC, Oakey RE: Oestrone sulphate in plasma from postmenopausal women and the effects of oestrogen and androgen therapy. Clin Endocrinol 13:461–471, 1980

    Google Scholar 

  27. Franz C, Watson D, Longcope C: Oestrone sulphate and dehydroenpiandrosterone sulphate in normal subjects and men with cirrhosis. Steroids 34:563–573, 1979

    PubMed  Google Scholar 

  28. Roberts KD, Rochefort JG, Bleau G, Chapdelaine A: Plasma oestrone sulphate levels in postmenopausal women. Steroids 35:179–187, 1980

    PubMed  Google Scholar 

  29. Noel CT, Reed MJ, Jacobs H, James VHT: The plasma concentration of oestrone sulphate in postmenopausal women: lack of diurnal variation, effect of ovariectomy, age and weight. J Steroid Biochem 14:1101–1105, 1981

    PubMed  Google Scholar 

  30. Heap RB, Haman M, Fleet IR: Transport of oestrone sulphate by the mammary gland. J Endocrinol 101:221–230 1984

    PubMed  Google Scholar 

  31. Ruder JJ, Loriaux L, Lipsett MB: Oestrone sulphate: production rate and metabolism in man. J Clin Invest 51:1020–1033, 1972

    PubMed  Google Scholar 

  32. Nimrod A, Ryan KJ: Aromatisation of androgens by human abdominal and breast fat tissue. J Clin Endocrinol Metab 40:367–372, 1975

    PubMed  Google Scholar 

  33. Schindler AE, Ebert A, Friedrich E: Conversion of androstenedione to oestrone by human fat tissue. J Clin Endocrinol Metab 35:627–630, 1972

    PubMed  Google Scholar 

  34. Frost PG, Reed MJ, James VHT: The aromatisation of androstenedione by human adipose and liver tissue. J Steroid Biochem 13:1427–1431, 1980

    PubMed  Google Scholar 

  35. Folkerd EJ, James VHT: The activity of 17β-hydroxysteroid dehydrogenase in human adipose tissue. Abstr 16, Soc for Endocrinology Meeting (161st), 26–27 November 1980

  36. Rizkallah TH, Tovell HMM, Kelly WC: Production of oestrone and fractional conversion of circulating androstenedione to oestrone in women with endometrial carcinoma. J Clin Endocrinol Metab 40:1045–1056, 1975

    PubMed  Google Scholar 

  37. MacDonald PC, Edmon CD, Hemsell DL, Porter JC, Siiteri PK: Effect of obesity on conversion of plasma androstenedione to oestrone in post-menopausal women with and without endometrial cancer. Am J Obstet Gynecol 130:448–455, 1978

    PubMed  Google Scholar 

  38. Lehninger AL: Biochemistry: the Molecular Basis of Cell Structure and Function. Worth Publishers, New York, 1977, pp 836–837

    Google Scholar 

  39. Preschtel K: Cited in Barth V: Atlas of Diseases of the Breast. Year Book Medical Publishers, Chicago, 1979,p 11

    Google Scholar 

  40. Chan PC, Dao TL: Enhancement of mammary carcinogenesis by a high fat diet in Fischer, Long-Evans and Sprague-Dawley rats. Cancer Res 41:164–167, 1981

    PubMed  Google Scholar 

  41. Carroll KK, Hopkins GJ: Dietary polyunsaturated fat versus saturated fat in relation to mammary carcinogenesis. Lipids 14:155–158, 1979

    PubMed  Google Scholar 

  42. Dao TL, Chan PC: Hormones and dietary fat as promoters in mammary carcinogenesis. Environ Health Perspect 50:219–225, 1983

    PubMed  Google Scholar 

  43. Editorial. Eskimo diets and diseases. Lancet i:1139–1140, 1983

    Google Scholar 

  44. Beer AE, Billingham RE: Adipose tissue, a neglected factor in aetiology of breast cancer? Lancet ii:296, 1978

    Google Scholar 

  45. Petrakis NL, Ernster VL: Adipose tissue and aetiology of breast cancer. Lancet ii:1001, 1978

    Google Scholar 

  46. Donegan WL, Jayich S, Koehler MR, Donegan JH: The prognostic implications of obesity for the surgical cure of breast cancer. Breast Diseases of the Breast 4:14–17, 1978

    Google Scholar 

  47. de Waard F: The epidemiology of breast cancer: review and prospects. Int J Cancer 4:577–586, 1969

    PubMed  Google Scholar 

  48. Mirra AP, Cole P, MacMahon B: Breast cancer in an area of high parity, Sao Paulo, Brazil. Cancer Res 31:77–83, 1971

    PubMed  Google Scholar 

  49. Lin TM, Chen KP, MacMahon B: Epidemiological characteristics of cancer of the breast in Taiwan. Cancer 27:1497–1504, 1971

    PubMed  Google Scholar 

  50. Adami HO, Rimesten A, Stenkvist B, Vegelius J: Influence of height, weight and obesity on risk of breast cancer in an unselected Swedish population. Brit J Cancer 36:787–792, 1977

    PubMed  Google Scholar 

  51. Petrakis NL, Maack CA, Lee RE, Lyon M: Mutagenic activity in nipple aspirates of human breast fluid. Cancer Res 40:188–189, 1980

    PubMed  Google Scholar 

  52. Rosenthal HE, Pietrzak E, Slaunwhite WR, Sandberg AA: Binding of oestrone sulphate in human plasma. J Clin Endocrinol Metab 34:805–813, 1972

    PubMed  Google Scholar 

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Hawkins, R.A., Thomson, M.L. & Killen, E. Oestrone sulphate, adipose tissue, and breast cancer. Breast Cancer Res Tr 6, 75–87 (1985). https://doi.org/10.1007/BF01806013

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