Differential metabolism of dehydroepiandrosterone sulfate and estrogen conjugates by normal or malignant AXC/SSh rat prostate cells and effects of these steroid conjugates on cancer cell proliferation in vitro.
Normal AXC/SSh rat ventral prostate and clonally derived AXC/SSh rat prostate cancer cells were evaluated for ability to metabolize estrone sulfate (E1S), estrone glucuronide (E1G), or dehydroepiandrosterone sulfate (DHEAS). Both normal and malignant prostate cells converted E1S to estrone. Neither normal nor malignant prostate cells had significant ability to metabolize DHEAS to DHEA, indicating differential specificity of prostate sulfatases(s) for estrogen and androgen sulfates. Both normal and neoplastic prostate cells possess beta-glucuronidase which hydrolyzed E1G to estrone. To assess potential physiologic consequences of these enzymatic activities, we determined the effect of steroid conjugates on in vitro proliferation of selected clonal lines of AXC/SSh rat prostate cancer cells. DHEAS, 10(-6) to 10(-9) M in decade intervals, did not affect in vitro proliferation of AXC/SSh prostate cancer cells; however, 10(-5) M DHEAS decreased in vitro proliferation of these cells. Neither E1S nor E1G, 10(-5) to 10(-9) M in decade intervals, affected in vitro proliferation of AXC/SSh prostate cancer cells. These findings suggest that low residual levels of steroid conjugates, which are not removed by charcoal stripping of serum, do not affect demonstrated in vitro androgen modulation of AXC/SSh rat prostate cancer cell proliferation (Cancer Res. 46, 3775-3781, 1986).
Huot
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Department of Cellular and Molecular Biology, Southwest Foundation for Biomedical Research, San Antonio, TX 78284.
Shain
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SA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate; D004966:Estrogens, Conjugated (USP) / Q000378:metabolism*; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051381:Rats
D004966:Estrogens, Conjugated (USP); C015856:estrone-3-glucuronide; D004970:Estrone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; C017296:estrone sulfate