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Oestrogen uptake and metabolism in vivo

Published online by Cambridge University Press:  05 December 2011

V. H. T. James
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
M. J. Reed
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
E. F. Adams
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
M. Ghilchick
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
L. C. Lai
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
N. G. Coldham
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
C. J. Newton
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
A. Purohit
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
A. M. Owen
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
A. Singh
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
S. Islam
Affiliation:
Department of Chemical Pathology, St Mary's Hospital Medical School, London W2 1PG, U.K.
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Synopsis

Uptake of oestrogens into breast tissue and their subsequent metabolism can be studied by infusing radio-labelled steroids into volunteer patients. Such studies show that oestradiol is preferentially accumulated in breast tumours, oestradiol concentrations exceeding those of oestrone. This contrasts with plasma, in which oestrone concentrations in postmenopausal women are greater than those of the oestradiol. This observation suggests that tissue factors can modulate local oestrogen metabolism, and thus local steroid concentrations.

We have studied the local production of oestrogens from androgen, and also the interconversion of the major oestrogens, oestrone and oestradiol. Using isotopic techniques, it is possible to calculate the proportion of endogenous oestrogen produced from androgen, as opposed to uptake from the circulation. These studies suggest that a very variable proportion of tissue oestrogen derives from endogenous synthesis. After administration of aromatase inhibitors, aromatase activity is substantially inhibited, both in vivo and in vitro.

Relative oestrogen concentrations are determined in part by the activity of oestradiol dehydrogenase. In breast tissue, dehydrogenase activity is present and this is modified by various factors, including androgens. In addition, we have demonstrated that normal, benign and malignant breast tissues produce factors which can modulate both growth and dehydrogenase activity of cancer cells in vitro.

We conclude that breast tissue is a site of synthesis of oestrogens, and that a number of factors can affect their local concentration. Tumour cells produce growth factors which can influence steroid metabolism, and may thus be able to enhance favourably their own endocrine environment.

Type
Research Article
Copyright
Copyright © Royal Society of Edinburgh 1989

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References

Adams, E. F., Newton, C. J., Braunsberg, H., Shaikh, N., Ghilchik, M. W. & James, V. H. T. 1988a. Effects of human breast fibroblasts on growth and 17β-oestradiol dehydrogenase activity of MCF-7 cells in culture. Breast Cancer Research and Treatment 11, 165172.CrossRefGoogle ScholarPubMed
Adams, E. F., Newton, C. J., Tait, G. H., Braunsberg, H., Reed, M. J. & James, V. H. T. 1988b. Paracrine influence of human breast stromal fibroblasts on breast epithelial cells: secretion of a polypeptide which stimulates reductive 17β-oestradial dehydrogenase activity. International Journal of Cancer 42, 119122.CrossRefGoogle ScholarPubMed
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