This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Adams, J. B. Articles by Clarke, C. Search for Related Content PubMed PubMed Citation Articles by Adams, J. B. Articles by Clarke, C.

Adrenal Dehydroepiandrosterone and Human Mammary Cancer¹

School of Biochemistry, University of New South Wales, Sydney, Australia

A hypothesis implicating adrenal dehydroepiandrosterone (DHEA) (sulfate) in the etiology of human breast cancer of the "adrenal" or "Western" type has been presented (Adams, J. B. Steroid Hormones and Human Breast Cancer. An Hypothesis. Cancer, 40: 325–333, 1977). High concentrations of DHEA sulfate in the blood provide a potentially high flux of the free steroid to mammary tumors, due to the presence therein of a sulfatase. The free steroid, in turn, is metabolized by human mammary tumors in vitro to 5-androstene-3ß,17ß-diol (ADIOL) and 7-hydroxydehydroeplandrosterone. It has now been found that ADIOL when administered s.c. to immature female rats will deplete the estrogen receptor in the uterine cytosol. Similarly, dimethylbenzanthracene-induced rat mammary tumors, when incubated in vitro with 1 µM ADIOL, show translocation of the estrogen receptor from cytosol to the nucleus, as measured by exchange assays. The magnitude of depletion of cytosol estrogen receptor by ADIOL was less than that obtained with 17ß-estradiol, studied at 0.03 µM concentrations, but greater than that with 1 µM dihydrotestosterone. Among a wide group of C₁₉ steroids examined as possible inhibitors of estrogen sulfotransferase, both DHEA and ADIOL showed marked inhibitory properties. By contrast, both 7- and 7ß-hydroxydehydroepiandrosterone showed negligible inhibitory effects. This paralleled previous findings on the influence of a 7-hydroxyl group in modifying the ability of ADIOL to compete effectively for the estrogen receptor. Thus the high levels of 7-hydroxylase found in human mammary tumors, and acting on both DHEA and ADIOL, may function in controlling the intracellular concentrations of these steroids.

¹ Presented at the John E. Fogarty International Center Conference on Hormones and Cancer, March 29 to 31, 1978, Bethesda, Md. Supported by grants from the Australian National Health and Medical Research Council.

² To whom requests for reprints should be addressed, at School of Biochemistry, University of N.S.W., P. O. Box 1, Kensington, N. S. W. 2033 Australia.