Can estrone sulfate stimulate mammary tumor growth in rats?

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Estradiol concentrations in human breast tumors are similar before and after menopause, even though plasma levels are 5- to 60-fold lower after menopause. How high estrogen levels are maintained in postmenopausal tumor tissue is unknown, but plasma estrone sulfate could be a precursor for estradiol synthesis in the tissue. In postmenopausal women, plasma estrone sulfate levels are 30-fold higher than free estradiol levels, and estrone sulfatase is present in many tissues, including breast tumors, supporting this hypothesis.

The researchers tested whether externally administered estrone sulfate could stimulate a carcinogen-induced, hormone-dependent rat mammary tumor and measured its conversion to free estrone and estradiol. Castrated rats with nitrosomethylurea-induced mammary tumors received infusions of estradiol as a control or estrone sulfate for 14 days. Low doses of estradiol significantly increased tumor volume, while higher amounts paradoxically inhibited growth. Estrone sulfate infusions significantly increased tumor volume compared with that observed in castrated animals on both days 7 and 14 of infusion.

To test conversion during this protocol, the researchers substituted 3H-estrone sulfate for the unlabeled steroid and again infused castrated animals for 14 days. At days 7, 10 and 14, 18–26% of estrone sulfate was converted to free estrone and 9–16% to free estradiol. There were no significant differences between the two doses used, and conversion rates remained stable during infusion. Radioimmunoassay of free estradiol in plasma during estrone sulfate infusions also demonstrated conversion to free estradiol.

The findings show that externally administered estrone sulfate can stimulate mammary tumor growth in castrated animals and support the possibility that it is an important source of estradiol in tumor tissue.