Dehydroepiandrosterone-fatty acid esters in human plasma: formation, transport and delivery to steroid target tissues.
In addition to dehydroepiandrosterone (DHEA) sulfate (S), the human plasma also contains a second form of DHEA ester: DHEA-fatty acid esters (DHEA-FA). In the human adult, the plasma concentrations of DHEA-FA, DHEA and DHEAS are in the range of 6, 12 and 2000 nM respectively. Although the adrenal is responsible for almost all production of DHEAS in the circulation, DHEA-FA is formed from DHEA by an enzyme present in the circulation. Our work has clearly demonstrated that lecithin-cholesterol acyltransferase, localized on high density lipoprotein, is responsible for DHEA-FA production. Once DHEA-FA is formed, it is subsequently transferred to very low density lipoprotein (VLDL) and low density lipoprotein (LDL), like cholesteryl esters. Plasma lipoproteins contain at least 90% of circulating DHEA-FA of which 40% are found in the LDL fraction. Analysis of the fatty acid composition of tritiated DHEA-FA-labelled LDL ([3H]DHEA-FA-LDL) indicated the prevalence of DHEA-linoleate/palmitoleate and DHEA-oleate. Treatment of [3H]steroid-FA-LDL with charcoal does not remove radioactivity, thus suggesting that the non-polar steroid is incorporated into the central non-polar core of the lipoproteins. Incubation of [3H]DHEA-FA-LDL with ZR-75-1 breast cancer cells produced a time-dependent increase in labeled non-conjugated steroids in the cell culture medium, whereas the levels of tritiated DHEA-FA decreased. Lipoidal radioactivity in cells increased with time, but non-conjugated radioactivity associated with the cells showed no such increase. HPLC analysis of the culture medium indicated the presence of tritiated DHEA and androst-5-one-3 beta, 17 beta-diol. Our study indicates that circulating DHEA-FA incorporated into lipoproteins may indeed act as a substrate for potent steroid formation following their entry into steroid target cells.
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MRC Group in Molecular Endocrinology, CHUL Research Center, Quebec, Canada.
Provost
P R
PR
Roy
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Gauthier
M C
MC
Bélanger
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A
D000311:Adrenal Glands / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism*; D004952:Esters; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005260:Female; D006066:Gonads / Q000378:metabolism; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D010920:Placenta / Q000378:metabolism
D004952:Esters; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D003687:Dehydroepiandrosterone; D007862:Phosphatidylcholine-Sterol O-Acyltransferase