Two antiatherogenic effects of progesterone on human macrophages; inhibition of cholesteryl ester synthesis and block of its enhancement by glucocorticoids

Wanli Cheng, Ontario D. Lau, Nada A. Abumrad

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The effects of progesterone and estradiol on cholesteryl ester (CE) formation by monocyte-derived human macrophages were examined. Formation was assessed from incorporation of 14C-cholesterol during a 20-h incubation with hormone and from that of 3H-oleate (3 h) after hormone removal. Progesterone inhibited cholesterol into CE and decreased CE cellular levels. Inhibition: 1) was reversed by progesterone removal; 2) was independent of the progesterone receptor (not blocked by the receptor antagonist RU40555); and 3) exhibited specific structural requirements; 11α-OH-progesterone was inhibitory, whereas its stereoisomer 11β-OH-progesterone was not. In contrast to progesterone, estradiol was ineffective. We had reproved that dexamethasone enhanced CE accumulation by human macrophages (1). In this study, we describe similar effects of the endogenous steroid, cortisol, and of the most widely prescribed glucocorticoid, prednisolone. Both steroids increased CE formation from two folds, in the presence of cholesterol- liposomes, to five folds, in the presence of modified low-density lipoprotein. Progesterone (0.1-1 μmol/L), added during glucocorticoid treatment, blocked this increase. The progesterone block: 1) was duplicated by the steroid receptor inhibitor RU40555; 2) was not reversed by hormone removal; and 3) reflected inhibition of glucocorticoid-induced increases in messenger RNA for acyl-CoA-cholesterol:acyl transferase. Thus, progesterone exerted two effects on macrophages: it acutely inhibited CE formation, and it prevented glucocorticoid-induced increases in acyl-CoA-cholesterolacyl transferase gene expression and CE synthesis.

Original languageEnglish
Pages (from-to)265-271
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume84
Issue number1
DOIs
StatePublished - Jan 23 1999
Externally publishedYes

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