title: Dehydroepiandrosterone reduces preadipocyte proliferation via androgen receptor.
abstract: Several studies have suggested that both testosterone and dehydroepiandrosterone (DHEA) have weight-reducing and antidiabetic effects, especially in rodent studies; however, the precise mechanism of their action remains unclear. Here, we investigated the effect of DHEA on cell growth in adipose tissue. The appearance of senescence-associated β-galactosidase in stromal vascular fraction (SVF) isolated from Otsuka Long-Evans Tokushima fatty rats, an animal model of inherent obese type 2 diabetes, was prevented by DHEA administration. Next, the effects of DHEA and testosterone were compared in vivo and in vitro to evaluate whether these hormones influence cell growth in adipose tissue. Both DHEA and testosterone reduced body weight and epididymal fat weight equivalently when administered for 4 wk. To assess the effect of DHEA and testosterone on cell growth in adipose tissue, 5-bromo-2'-deoxyuridine (BrdU) uptake by SVF was measured. Quantification analysis of BrdU uptake by examining DNA isolated from each SVF revealed that treatment with DHEA and testosterone reduced cell replication. These results indicated that DHEA- and testosterone-induced decreased adiposity was associated with reduced SVF growth. Incubation with DHEA and testosterone equally decreased BrdU uptake by 3T3-L1 preadipocytes. Pretreatment with the androgen receptor (AR) inhibitor flutamide, but not the estrogen receptor inhibitor fulvestrant, abolished these effects. Knockdown of AR with siRNA also inhibited DHEA-induced decreases in BrdU uptake. These results suggest that DHEA-induced growth suppression of preadipocytes is mediated via AR. Therefore, both DHEA and testosterone similarly decrease adipocyte growth possibly via a common mechanism.
authors.affiliation: Dept. of General Internal Medicine, Gifu Univ. Graduate School of Medicine,Yanagido, Gifu, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Fujioka
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kajita
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Wu
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hanamoto
authors.forename: Takahide
authors.initials: T
authors.lastname: Ikeda
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mori
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Isao
authors.initials: I
authors.lastname: Nagano
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ishizuka
mesh_terms: D017667:Adipocytes / Q000187:drug effects*; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D048430:Cell Shape; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D043171:Chromosomal Instability / Q000187:drug effects; D004249:DNA Damage; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D005990:Glycerol / Q000378:metabolism; D008297:Male; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000187:drug effects*; D017154:Stromal Cells / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000963:Antimetabolites; D011944:Receptors, Androgen; D014280:Triglycerides; D013739:Testosterone; D003687:Dehydroepiandrosterone; D001616:beta-Galactosidase; D001973:Bromodeoxyuridine; D005990:Glycerol