A novel synthetic androgen receptor ligand, S42, works as a selective androgen receptor modulator and possesses metabolic effects with little impact on the prostate.
We identified a novel synthetic steroid, S42, as a promising candidate of selective androgen receptor (AR) modulator. Results of the whole-cell binding assay using COS-7 cells exogenously expressing various steroid receptors indicated that S42 specifically binds to AR and progesterone receptor. When orchiectomized Sprague Dawley rats were administered with S42 for 3 wk, the muscle weight of the levator ani was increased as markedly as that induced by 5alpha-dihydrotestosterone (DHT), but the weight of the prostate was not elevated at any doses in contrast to DHT. The plasma concentrations of gonadotropin and adiponectin, those down-regulated by DHT, were unaffected by S42. In addition, although the plasma triglyceride level was unaffected by DHT, it was significantly reduced by S42. This effect of S42 was associated with suppression of the SRBP-1c-mediated lipogenic and insulin-desensitizing pathway in the liver and visceral fat. Taken together, S42 works as an AR agonist in muscle and as an AR antagonist in the prostate, pituitary gland, and liver, accompanying beneficial potentials on lipid metabolism.
Min
Liu
L
Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan.
Yanase
Toshihiko
T
Tanaka
Tomoko
T
Fan
WuQiang
W
Nomura
Masatoshi
M
Kawate
Hisaya
H
Okabe
Taijiro
T
Takayanagi
Ryoichi
R
Nawata
Hajime
H
D041721:3T3-L1 Cells; D045930:Anabolic Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000728:Androgens; D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004353:Drug Evaluation, Preclinical; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*; D013256:Steroids / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D045930:Anabolic Agents; D059002:Androgen Receptor Antagonists; D000728:Androgens; D008024:Ligands; D011944:Receptors, Androgen; C546432:SARM42 compound; D013256:Steroids; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides