Dehydroepiandrosterone sulfotransferase as a possible shunt for the control of steroid metabolism in human mammary carcinoma.

Human primary mammary tumors were examined to determine what factors were of importance in deciding relative rates of sulfurylation of dehydroepiandrosterone and 17beta-estradiol, such rates having been shown to correlate with the patient's prognosis and response to adrenalectomy (T. L. Dao and P.R. Libby. Enzymic Synthesis of Steroid Sulfate by Mammary Cancer and Its Clinical Implications. Natl. Cancer Inst. Monographs, 34: 205-210, 1971). The sulfurylation of dehydroepiandrosterone and 17beta-estradiol was studied in 41 tumors in vitro using tumor cytosol, adenosine triphosphate, [35S]SO42-, Mg2+, and added steroid. Six tumors showed no sulfurylating ability, 9 sulfurylated dehydroepiandrosterone at a rate greater than that for 17beta-estradiol (ratio, greater than 1), and 26 sulfurylated dehydroepiandrosterone at a rate lower than that for 17beta-estradiol (ratio, less than 1). Evidence was obtained that low levels of dehydroepiandrosterone sulfotransferase were responsible for ratios of less than 1, in many instances. Adenosine 3'-phosphate 5'-phosphosulfate synthesis and steroid sulfotransferase activities were measured in 30 tumors. A significant correlation was found between synthesis of the former and levels of estrogen sulfotransferase, but this relationship did not hold for dehydroepiandrosterone sulfotransferase, again due to low levels of this enzyme in many tumors. It is suggested that dehydroepiandrosterone sulfate formation in the tumors is mainly controlled by the sulfotransferase, which acts as a shunt in regulating the level of free dehydroepiandrosterone, and related compounds, available for metabolism to steroids influencing the growth of mammary epithelial cells.