The regulation of HSL and LPL expression by DHT and flutamide in human subcutaneous adipose tissue.
Clinical observations suggest a role for testosterone in the accumulation of central adiposity and with an associated increased risk of disease. To date, no human study has analysed the role of dihydrotestosterone (DHT) on adipose tissue mass regulation in vitro. This study investigated the role of DHT and androgen receptors (AR) in the regulation of lipolysis and lipogenesis by examining the key enzymes hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) respectively. Isolated abdominal subcutaneous adipocytes (Scad) (n = 15) were treated with either DHT (10(-7)-10(-9) m), an antiandrogen, flutamide (FLT: 10(-7)-10(-9) m) or a combination of DHT (10(-7)-10(-9) m) with FLT (10(-8) m). Relative protein expression of HSL, LPL and AR was determined. In Scad, DHT inhibited HSL expression maximally at 10(-9) m (0.7 +/- 0.4**; p < 0.01**) compared with control (control: 1.0 +/- (s.e.m.) 0.0), whereas LPL protein expression was stimulated at DHT10(-9) m (2.22 +/- 0.48*; p < 0.05*). Glycerol release assay results correlated with HSL expression data. LPL expression was reduced at all doses with combinations of DHT + FLT compared with DHT alone. Androgen receptor expression studies showed an inverse correlation with DHT, whereas DHT + FLT reduced AR expression. These studies indicate that DHT may alter HSL and LPL expression, whereas only LPL expression appears mediated by AR. These findings suggest a physiological role for DHT in the control of adipose tissue mass in women, and indicate that androgens may also play an important role in regulating lipid metabolism.
Anderson
L A
LA
Department of Medicine, University of Birmingham, Division of Medical Sciences, Edgbaston, Birmingham, UK.
McTernan
P G
PG
Harte
A L
AL
Barnett
A H
AH
Kumar
S
S
D017667:Adipocytes / Q000201:enzymology*; D000273:Adipose Tissue / Q000201:enzymology*; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D005485:Flutamide / Q000494:pharmacology*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008875:Middle Aged; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D002787:Sterol Esterase / Q000378:metabolism*
D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D005485:Flutamide; D002787:Sterol Esterase; D008071:Lipoprotein Lipase