Hostname: page-component-77c89778f8-n9wrp Total loading time: 0 Render date: 2024-07-16T17:47:10.389Z Has data issue: false hasContentIssue false
  • English
  • Français

Biosynthesis of active oestrogens in the breast

Published online by Cambridge University Press:  05 December 2011

A. Vermeulen  and
J. P. Deslypere
A. Vermeulen
Affiliation:
Department of Endocrinology, University Hospital, De Pintelaan, 185, B 9000 Gent, Belgium
J. P. Deslypere
Affiliation:
Department of Endocrinology, University Hospital, De Pintelaan, 185, B 9000 Gent, Belgium
Get access

Synopsis

It is generally accepted that sex hormones play a role in the development of mammary cancer and it is a reasonable assumption that tissue concentration of oestrogens and their androgen precursors, as well as the activity of oestrogen synthetising or metabolising enzymes, may be valuable parameters of hormone dependency. Except for the sulphate conjugates and for testosterone, androgen and oestrogen levels are higher in mammary tissue (ng/g) than in plasma (ng/ml) and as distinct from plasma, tissue oestradiol (the active oestrogen) levels are higher than oestrone levels. Moreover, oestradiol levels are higher in oestrogen-receptor-positive tissues.

Sex hormone levels in mammary tissue find their origin in uptake from plasma and in local synthesis. It is unlikely that local aromatase activity accounts for a large fraction of tissue oestrogens but sulphatase activity may be an important determinant of tissue oestrogen concentration. The major precursors of tissue oestrogens are androstenedione and oestrone sulphate respectively, yielding oestrone which is transformed by the 17β-hydroxysteroid dehydrogenase to oestradiol. However, the reverse reaction, conversion of E2 into E1, is much more active and is inversely correlated to dehydroepiandrosterone (sulphate) concentration, which inhibits non-competitively the conversion of E2 into E1. This E2DH activity is higher in E2R positive tumours, suggesting that E2DH is a good marker of hormone dependency. As to prognostic factors, a follow-up study concerning sixty-two postmenopausal women, with a follow up of at least four years, revealed that in the recurrence group (n = 17 ), besides E2R and PgR concentrations, all hormone concentrations as well as E2DH activity were also lower than in the disease-free group.

Type
Research Article
Information
Proceedings of the Royal Society of Edinburgh, Section B: Biological Sciences , Volume 95: Oestrogen and the Human Breast , 1989 , pp. 195 - 201
Copyright
Copyright © Royal Society of Edinburgh 1989

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abul-Hajj, Y., Iverson, R. & Kiang, D. T. 1979. Aromatization of androgens by human breast cancer. Steroids 33, 205–223.CrossRefGoogle ScholarPubMed
Abul-Hajj, Y. 1982. Formation of estradiol 17β-fatty acyl-17 esters in mammary tumours. Steroids 40, 149–156.CrossRefGoogle Scholar
Bonney, R. M., Reed, M. J., Davidson, K., Beranek, R. A. & James, V. H. T. 1983. The relationship between 17β-hydroxysteroid dehydrogenase activity and oestrogen concentration in human breast tumours and in normal breast tissue. Clinical Endocrinology 19, 727–739.CrossRefGoogle Scholar
Bradlow, H. L. 1982. A reassessment of the role of breast tumor aromatization. Cancer Research 42 (suppl), 3382S–3386S.Google ScholarPubMed
Bruning, P. F., Bonfier, J. M. G. & Hart, A. A. M. 1985. Non protein bound oestradiol, sex hormone binding globulin, breast cancer and breast cancer risk. British Journal of Cancer 51, 479–484.CrossRefGoogle ScholarPubMed
Deshpande, N., Carson, P., De Martino, L. & Tarquini, A. 1976. Biogenesis of steroid hormones by human mammary gland in vivo and in vitro. European Journal of Cancer 12, 271–276.CrossRefGoogle ScholarPubMed
Deslypere, J. P. 1984. Invloed van de leeftijd op de geslachtshormoonspiegels in plasma en in de weefsels bij de mens (Ph.D.Thesis, University of Gent).Google Scholar
Duvivier, J., Colin, C., Hustin, J., Albert, A., Lavigne, J., Dive, G. & Montfort, F. 1981. Comparison of levels of cytosol estrogen receptors with arterial and venous concentrations of gonadic steroids in mammary tumors. Clinica Chimica Acta 112, 21–32.CrossRefGoogle ScholarPubMed
Folca, P. J., Glascock, R. F. & Irvine, W. T. 1962. Studies with tritium labelled hexestrol in advanced breast cancer. Lancet 2, 796–798.Google Scholar
Folkerd, E. J. & James, V. H. T. 1983. Aromatization of steroids in peripheral tissues. Journal of Steroid Biochemistry 19, 687–690.CrossRefGoogle ScholarPubMed
Fournier, S., Allali, F., Durand, J. C., Sterkers, N., Debeztrand, P. H., Diclold, N., Martin, P. M., Kuttenn, F. & Mauvais Jarvis, P. 1985. Evaluation de l'activité enzymatique 17β-hydroxysteroid deshydrogenase comme marqueur de l'hormonodépendence du sein. Pathologie–Biologie 33, 659–664.Google Scholar
James, V. H. T., McNeil, J. M., Beranek, P. A., Bonney, R. C. & Reed, M. J. 1986. The role of tissue steroids in regulating aromatase and oestradiol 17β-hydroxysteroid dehydrogenase activity in breast and endometrial cancer. Journal of Steroid Biochemistry 25, 787–900.CrossRefGoogle Scholar
Janocko, L. & Hochberg, R. B. 1983. Estradiol fatty acids occur naturally in human blood. Science 222, 1334–1336.CrossRefGoogle ScholarPubMed
Janocko, L., Larner, J. M. & Hochberg, R. B. 1984. The interaction of C17 esters of estradiol with the estrogen receptors. Endocrinology 114, 1180–1186.CrossRefGoogle Scholar
Larner, J. M., Eisenfeld, A. J. & Hochberg, R. B. 1985. Synthesis of estradiol fatty acid esters by human breast tumors: fatty acid composition and comparison to estrogen and progesterone receptor content. Journal of Steroid Biochemistry 32, 637–643.CrossRefGoogle Scholar
Li, R. & Adams, J. B. 1981. Aromatization of testosterone and estrogen receptor levels in human breast cancer. Journal of Steroid Biochemistry 14, 269–272.CrossRefGoogle ScholarPubMed
MacMahon, B., Cole, P. & Brown, J. 1973. Etiology of human breast cancer: a review. Journal of the National Cancer Institute 50, 21–42.CrossRefGoogle ScholarPubMed
Miller, W. R., Hawkins, R. A. & Forrest, A. P. M. 1982. Significance of aromatase in breast cancer. Cancer Research 42, 3365–3368.Google Scholar
Miller, W. R. & Forrest, P. M. 1974. Oestradiol synthesis by human breast carcinoma. Lancet ii, 866–868.CrossRefGoogle Scholar
Moore, J. W., Clark, G. M. G. & Bulbrook, R. D. 1982. Serum concentrations of total and non-protein bound oestradiol in patients with breast cancer and normal controls. International Journal of Cancer 29, 17–21.CrossRefGoogle ScholarPubMed
Murayama, Y., Sakuma, T., Udagawa, H., Utsunomiya, Y., Okamoto, R. & Asano, K. 1979. Sex hormone binding globulin as a reliable indication of hormone dependency in human breast cancer. Annals of Surgery 190, 133–138.CrossRefGoogle Scholar
Pearlman, W. H., De Hertogh, R., Laumas, K. R. & Pearlman, M. R. J. 1969. Metabolism and tissue uptake of estrogens in women with advanced carcinoma of the breast. Journal of Clinical Endocrinology and Metabolism 29, 207–220.CrossRefGoogle ScholarPubMed
Perel, E., Danilescu, D., Kharlip, L., Blackstein, M. & Killinger, D. W. 1988. Steroid modulation of aromatase activity in human cultured breast carcinoma cells. Journal of Steroid Biochemistry 29, 393–399.CrossRefGoogle ScholarPubMed
Prudhomme, J. F., Mallet, C., Gompel, A., Lalardrie, J. P., Ochoa, C., Bone, A., Mauvais Jarvis, P. & Kuttenn, F. 1984. 17β-hydroxysteroid dehydrogenase activity in human epithelial cell and fibroblastic cultures. Endocrinology 114, 1483–1489.CrossRefGoogle Scholar
Reed, M. J., Cheng, R. W., Noel, T. C., Dudley, H. A. F. & James, V. H. T. 1983. Plasma levels of estrone, estronesulfate and estradiol and the percentage of unbound estradiol in postmenopausal women, with and without breast cancer. Cancer Research 43, 3940–3943.Google Scholar
Reed, M. J., Beranek, P. A., Franks, J. & James, V. H. T. 1986. The effect of glucocorticoids on the in vivo conversion of plasma androstenedione to estrone. Hormones and metabolic research 18, 635–637.CrossRefGoogle Scholar
Santner, S. J., Feil, P. D. & Santen, R. J. 1984. In situ estrogen production via the estrone sulphate pathway in breast tumors: relative importance versus aromatase pathway. Journal of Clinical Endocrinology and Metabolism 59, 29–34.CrossRefGoogle ScholarPubMed
Sherman, B. M. & Korenman, S. G. 1974. Inadequate corpus luteum function: a pathophysiological interpretation of human breast cancer epidemiology. Cancer 33, 1306–1311.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Siiteri, P. K. 1981. Extraglandular oestrogen formation and serum binding of oestradiol. Relationship to cancer. Journal of Endocrinology 89, 119–129.Google ScholarPubMed
Sirbasku, D. 1978. Estrogen-induction of growth factors specific for hormone-responsive mammary pituitary and kidney tumor cells. Proceedings of the National Academy of Sciences of the U.S.A. 75, 3786–3790.CrossRefGoogle ScholarPubMed
Tilson Mallet, N., Santner, S. J., Feil, P. D. & Santen, R. J. 1983. Biological significance of aromatase activity in human breast tumors. Journal of Endocrinology and Metabolism 57, 1125–1128.CrossRefGoogle Scholar
Van Landeghem, A. A. J., Poortman, J., Dimartino, L., Tarquini, A., Thyssen, J. H. H. & Schwarz, F. 1981. Plasma concentration gradient across human mammary tumors in vivo. Journal of Steroid Biochemistry 14, 741–747.CrossRefGoogle Scholar
Varela, R. M. & Dao, T. L. 1978. Estrogen synthesis and estradiol binding by human mammary tumors. Cancer Research 38, 2429–2433.Google ScholarPubMed
Vermeulen, A., Deslypere, J. P., Paridaens, R., Leclercq, G., Roy, F. & Heuson, J. C. 1986. Aromatase, 17β-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women. European Journal of Cancer and Clinical Oncology 22, 515–525.CrossRefGoogle Scholar
Wilking, M., Carlstrom, R., Gustafsson, S. A., Skoldefors, J. & Tollbom, O. 1980. Oestrogen receptors and metabolism of oestradiol sulfate in human mammary carcinoma. European Journal of Cancer and Clinical Oncology 16, 1339–1344.Google ScholarPubMed
Wysowski, D., Comstock, G. W., Helsing, K. J. & Lorrin Lau, H. 1987. Sex hormone levels in serum in relation to the development of breast cancer. American Journal of Epidemiology 125, 791–799.CrossRefGoogle Scholar