Esterification of dehydroepiandrosterone by human plasma HDL3

Leszczynski, D. E.; Schafer, R.M.; Perkins, E. G.; Jerrell, John P.; Kummerow, Fred A.

doi:10.1016/0167-4889(89)90245-0

Cited by 25 publications

(10 citation statements)

References 30 publications

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“…Probably, the mechanism of loose-binding of the hormones to membranes is in part comparable to that of cholesterol [19], [35]. The occasional presence of fatty acid-esterified sex hormones in blood (especially in lipoproteins) [36]–[38] has been attributed to their similarity with cholesterol, resulting in their trans-esterification [39].…”

Section: Discussionmentioning

confidence: 99%

Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

et al. 2012

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It is generally assumed that steroid hormones are carried in the blood free and/or bound to plasma proteins. We investigated whether blood cells were also able to bind/carry sex-related hormones: estrone, estradiol, DHEA and testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days, which induced overweight. The rats were fed the standard rat diet for 15 additional days to minimize the immediate effects of excess ingested energy. Controls were always kept on standard diet. After the rats were killed, their blood was used for 1) measuring plasma hormone levels, 2) determining the binding of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood with labeled hormones and determining the distribution of label between plasma and packed cells, discounting the trapped plasma volume, 4) determining free plasma hormone using labeled hormones, both through membrane ultrafiltration and dextran-charcoal removal. The results were computed individually for each rat. Cells retained up to 32% estrone, and down to 10% of testosterone, with marked differences due to sex and diet (the latter only for estrogens, not for DHEA and testosterone). Sex and diet also affected the concentrations of all hormones, with no significant diet effects for estradiol and DHEA, but with considerable interaction between both factors. Binding to RBC was non-specific for all hormones. Estrogen distribution in plasma compartments was affected by sex and diet. In conclusion: a) there is a large non-specific RBC-carried compartment for estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes, affected by sex, which hint at sex-related structural differences in RBC membranes; c) We postulate that the RBC compartment may contribute to maintain free (i.e., fully active) sex hormone levels in a way similar to plasma proteins non-specific binding.

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Section: Discussionmentioning

confidence: 99%

Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

et al. 2012

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“…Several plausible mechanisms for a beneficial effect of DHEAS on cardiovascular morbidity or mortality have been postulated; these include prevention of platelet aggregation (146), inhibition of macrophage accumulation in the intima as well as proliferation of smooth muscle cells from the media into the intima (147), interference with arterial uptake of cholesterol (148), suppression of superoxide radical formation (149), conversion of DHEA to estrogen (150), and binding of DHEA metabolite (androstenediol) to vacant estrogen receptors, and enhanced estrogen-like effects in men (151).…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Endogenous Sex Hormones and Cardiovascular Disease in Men

Muller

Schouw

Thijssen

et al. 2003

The Journal of Clinical Endocrinology &Amp; Metabolism

118

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Unlike women, men do not experience an abrupt reduction in endogenous sex hormone production. It has, however, become clear that an age-associated decrease in the levels of (bioactive) sex hormones does occur. Whether endogenous sex hormones have an impact on cardiovascular disease has for many years remained largely unknown, but during the last decade more attention has been drawn to the importance of testosterone, estrogens, and adrenal androgens in etiology, prevention, and treatment of male cardiovascular disease. The purpose of this article is to summarize the evidence currently available on the association between endogenous sex hormones and cardiovascular disease in males. Published studies dealing with the relationship between circulating levels of sex hormones and cardiovascular disease in males were reviewed. The studies reviewed in this article suggest that circulating endogenous sex hormones and estrogens have a neutral or beneficial effect on cardiovascular disease in men.

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“…ribonucleic acid interference; chromatography; dehydroepiandrosterone STEROID FATTY ACYL ESTERS (FAE) such as 17␤-estradiol-FAE (E 2 -FAE) and dehydroepiandrosterone-FAE (DHEA-FAE) belong to a unique family of naturally occurring hydrophobic hormone derivatives (15, 16). These steroids are esterified in a reaction catalyzed by plasma lecithin-cholesterol acyltransferase associated with high-density lipoprotein (HDL) particles and transported to other lipoprotein particles (14,18,30,35,42). The physiological role of steroid-FAE remains unclear.…”

mentioning

confidence: 99%

Role of lysosomal acid lipase in the intracellular metabolism of LDL-transported dehydroepiandrosterone-fatty acyl esters

Wang

Wang²,

Wähälä³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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H]DHEA-FAE entered cells via LDL receptor or LDL receptorrelated receptor-mediated uptake, followed by intracellular hydrolysis and further metabolism into 5␣-adione and 4-adione that were excreted from cells. Although LAL contributed to the deesterification of DHEA-FAE, it was not solely responsible for the hydrolysis. ribonucleic acid interference; chromatography; dehydroepiandrosterone STEROID FATTY ACYL ESTERS (FAE) such as 17␤-estradiol-FAE (E 2 -FAE) and dehydroepiandrosterone-FAE (DHEA-FAE) belong to a unique family of naturally occurring hydrophobic hormone derivatives (15, 16). These steroids are esterified in a reaction catalyzed by plasma lecithin-cholesterol acyltransferase associated with high-density lipoprotein (HDL) particles and transported to other lipoprotein particles (14,18,30,35,42). The physiological role of steroid-FAE remains unclear. E 2 -FAE have been considered as the storage form of active estrogen in lipoproteins and adipose tissues that may be released as an active unconjugated hormone (3). It has also been suggested that E 2 -FAE may act as an antioxidant, protecting lipoproteins against oxidation (17, 41). Our previous studies (4) in a cell culture model demonstrated that lipoprotein-associated E 2 -FAE can be transferred into target cells and hydrolyzed to free E 2 .Compared with E 2 -FAE that is present in picomolar concentration in the circulation, nanomolar concentrations of circulating DHEA-FAE have been reported (7,26). Moreover, its hydrolysis product, DHEA, is one of the relatively abundant adrenal steroids secreted in humans and the precursor of estrogens and androgens (24). In blood, Ͼ90% of DHEA-FAE is associated with lipoproteins (38, 39). We are interested in the intracellular hydrolysis and metabolic fate of lipoproteinbound DHEA-FAE in target tissues.In postmenopausal women, only trace amounts of E 2 are present in serum, the overwhelming majority of estradiol residing in adipose tissue, mostly in the form of FAE (3). This finding opens up the possibility that adipose tissue could constitute a reservoir of many other steroid-FAEs from which active steroid hormones could, in principle, be liberated by hydrolysis of the FAE bond. Therefore, we aimed at exploring possible hydrolytic mechanisms involved in generating free DHEA and identifying potential bioactive metabolites of DHEA generated in cells. Lysosomal acid lipase (LAL) is the enzyme responsible for the intracellular hydrolysis of LDLassociated cholesteryl esters (cholesteryl-FAE) that are taken up by LDL-receptor-mediated endocytosis (12). Because of the similar ring structure of DHEA and cholesterol, we investigated the possibility that DHEA-FAE is also hydrolyzed by LAL. We chose HeLa cells as a model to study the hydrolysis and metabolism of LDL-associated DHEA-FAE because these cells, derived from the reproductive tract, have previously been useful in the study cholesterol metabolism (19,22,37). Moreover, HeLa cells express LAL mRNA (1) and RNA silencing works very reproducibly in these cells. Thus we inv...

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Esterification of dehydroepiandrosterone by human plasma HDL3

Cited by 25 publications

References 30 publications

Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

Endogenous Sex Hormones and Cardiovascular Disease in Men

Role of lysosomal acid lipase in the intracellular metabolism of LDL-transported dehydroepiandrosterone-fatty acyl esters

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