Nonspecific and metabolic interactions between steroid hormones and human plasma lipoproteins |
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Authors: | D E Leszczynski R M Schafer |
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Affiliation: | (1) The Harlan E. Moore Heart Research Foundation, 503 S. Sixth Street, 61820 Champaign, IL |
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Abstract: | Previous observations demonstrated that steroid hormones associate with plasma lipoproteins. The objective of this study was
to estimate the relative importance of lipoproteins as steroid hormone binding agents in comparison to sex hormone binding
globulin, corticosteroid binding globulin, and albumin in both normal and hyperlipidemic human plasma. The 16 steroid hormones
and related metabolites included in the study were: androstanediol, androstenediol, androstenedione, androsterone, corticosterone,
cortisol, dehydroepiandrosterone, deoxycorticosterone, dihydrotestosterone, estradiol, estriol, estrone, 17α-hydroxyprogesterone,
pregnenolone, progesterone, and testosterone. The binding activity of these 16 steroid hormones with purified high density
lipoprotein (HDL), low density lipoprotein and very low density lipoprotein were separately evaluated by equilibrium dialysis
incubations to yield 48 steroid hormone-lipoprotein combinations for further study. In incubations with HDL, six steroid hormones
(androstenediol, dehydroepiandrosterone, dihydrotestosterone, estradiol, pregnenolone, and progesterone) were identified as
non-equilibrium, apparently due to metabolic conversion of the steroid hormones. The metabolic activity for the three Δ5-3β hydroxy steroids and estradiol appears to be fatty acid esterification by lecithin:cholesterol acyltransferase. The computer
program TRANSPORT, which was used to evaluate only the nonspecific steroid hormone-lipoprotein association levels in a 16×6
matrix at simultaneous equilibrium, indicated that lipoprotein-bound steroid hormones ranged from 1% for cortisol to 56% for
pregnenolone in normal human blood. Simulated projections of the increase in nonspecific steroid hormone association with
lipoproteins during hyperlipidemia are also presented. These results demonstrate how lipoproteins are likely to be important
in the transport and metabolism of steroid hormones in human plasma. |
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