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


OBJECTIVE
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.


METHODS
Tissue samples were obtained during elective surgery in University Central Hospital in the years 2008-2011.


METHODS
Women undergoing reduction mammoplasty (n = 27) or surgery for breast cancer (n = 16) participated in the study.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Folkhälsan Research Center, Biomedicum Helsinki C415, Haartmaninkatu 8, 00290 Helsinki, Finland.
Feng
F
Wang
Veera
V
Vihma
Maija
M
Badeau
Hanna
H
Savolainen-Peltonen
Marjut
M
Leidenius
Tomi
T
Mikkola
Ursula
U
Turpeinen
Esa
E
Hämäläinen
Elina
E
Ikonen
Kristiina
K
Wähälä
Christian
C
Fledelius
Matti
M
Jauhiainen
Matti J
MJ
Tikkanen
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015992:Body Mass Index; D001940:Breast / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism; D004952:Esters / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D008875:Middle Aged; D051381:Rats; D013256:Steroids / Q000378:metabolism; D002787:Sterol Esterase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism*
D004952:Esters; D005227:Fatty Acids; D013256:Steroids; D003687:Dehydroepiandrosterone; D004958:Estradiol; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase