TRANSFER OF DEHYDROEPIANDROSTERONE-FATTY-ACID AND PREGNENOLONE-FATTY-ACID ESTERS BETWEEN HUMAN LIPOPROTEINS

Dehydroepiandrosterone (DHEA)- and pregnenolone (PREG)-fatty acid este rs (FA) are formed in plasma high density lipoproteins (HDL), whereas they accumulate in very low density lipoproteins (VLDL, low density li poproteins (LDL), and HDL. We have hypothesized that these lipoidal st eroids could be transferred from HDL to VLDL and LDL by the cholestery l ester (CE) transfer protein (CETP), which mediates CE transfer activ ity in human plasma. In this study, we further investigated this hypot hesis. Lipoproteins and lipoprotein-deficient plasma (LPDP) were purif ied and analyzed by Western blots. LPDP was rich in CETP, in contrast to lipoprotein preparations, which contained very low amounts. Using t hese preparations in in vitro transfer assays, CE transfer from radiol abeled steroid ester-HDL to VLDL or LDL was only observed in the prese nce of LPDP. In contrast, time- and temperature-dependent transfer of DHEA-FA and PREG-FA were observed in the absence of LPDP. The addition of LPDP had no effect on the DHEA-FA transfer rate, whereas the PREG- FA transfer rate was increased. Moreover, in the absence of LPDP, no d ecrease in the transfer levels of DHEA-FA and PREG-FA was observed aft er the removal of CETP from lipoprotein preparations by immunoaffinity column chromatography. The PREG-FA transfer activity of LPDP was stud ied using the anti-CETP monoclonal antibody TP-2, which is known to bl ock the CE transfer activity of CETP, in the presence of LPDP, this an tibody led to a dose-dependent decrease in CE transfer activity, where as PREG-FA transfer activity was unaffected. In conclusion, we have sh own that DHEA-FA and PREG-FA are transferred from HDL to VLDL and LDL by a CETP-independent mechanism. There is a major difference in the tr ansport of lipoidal steroids by human lipoproteins compared to that of CE.