Fatty acyl esterification and deesterification of 17β-estradiol in human breast subcutaneous adipose tissue.

Adipose tissue has an important role in peripheral estrogen synthesis. One of the metabolic pathways of estradiol (E(2)) is its conversion to lipophilic fatty acyl esters. The aim was to study the metabolism of E(2) fatty acyl esters in adipose tissue and, specifically, the role of hormone-sensitive lipase (HSL) in steroid ester hydrolysis. Tissue samples were obtained during elective surgery in University Central Hospital in the years 2008-2011. Women undergoing reduction mammoplasty (n = 27) or surgery for breast cancer (n = 16) participated in the study. Two sc adipose tissue samples were taken from different quadrants of the breast. Radiolabeled steroids were incubated with tissue homogenate (esterase assay) or microsomal fraction (acyl transferase assay). E(2) and E(2) fatty acyl ester concentrations were determined by fluoroimmunoassay or liquid chromatography-tandem mass spectrometry. We evaluated the hydrolysis rate of E(2) fatty acyl esters as well as the esterification rate of E(2); we also related tissue concentrations of E(2) and E(2) esters to serum estrogen concentrations. Compared to esters of dehydroepiandrosterone and cholesterol, the hydrolysis of E(2) esters was much slower, whereas the esterification rate of E(2) was higher. The hydrolysis of E(2) esters in adipose tissue was reduced by 33-51% by inhibition of HSL. Estrogen concentration in sc adipose tissue was higher than in serum in both pre- and postmenopausal women. E(2) fatty acyl esters in adipose tissue surrounding the mammary gland may act as a reservoir for conversion back to biologically active E(2). This is partly dependent on HSL activity.