Fatty acid esters of steroids: Synthesis and metabolism in lipoproteins and adipose tissue

At the end of the last century ideas concerning the physiological role of the steroid fatty acid ester family were emerging. Estrogens, fatty acylated at C-17 hydroxyl group and incorporated in lipoproteins were proposed to provide antioxidative protection to these particles. A large number of studies involving non-estrogenic adrenal steroids, and their fatty acylated forms, demonstrated their lipoprotein-mediated transport into cells and subsequent intracellular activation, suggesting a novel transport mechanism for lipophilic steroid derivatives. After these important advances the main focus of interest has shifted away from C-19 and C-21 steroids to fatty acylated estrogens. However, interest in their lipoprotein-mediated transport has decreased because only minute amounts of these derivatives were detected in circulating lipoproteins, and their antioxidative activity remained unconfirmed under physiological circumstances. It now appears that the overwhelming majority of estradiol in postmenopausal women resides in adipose tissue, most of it in esterified form. This is poorly reflected in plasma levels which are very low. Recent data suggest that estrogen fatty acid esters probably represent a storage form. The future focus of investigation is likely to be on firstly, the enzymatic mechanisms regulating the esterification and de-esterification of estradiol and other steroids residing in adipose tissue and secondly, on the role of insulin and other hormones in the regulation of these enzymatic mechanisms. Thirdly, as a large proportion of fatty acid esterified C-19 and C-21 non-estrogenic steroids is transported in lipoproteins and as they are important precursors of androgens and estrogens, this field should be investigated further.

Research highlights► Steroid fatty acid esters are transported in the circulation by lipoproteins. ► A major part of estradiol in the female adipose tissue is in fatty acid esterified form. ► Enzymatic mechanisms regulating the esterification of steroids are of interest.