Androgenic and antiandrogenic effects and expression of androgen receptor in mouse embryonic stem cells.
OBJECTIVE
To investigate the effects of androgen and antiandrogen and the expression of androgen receptor on mouse embryonic stem cells (ESCs) and the inner cell mass.


METHODS
Controlled laboratory study.


METHODS
Academic university hospital.


METHODS
Blastocysts from mice developed at the Institute for Cancer Research and 129/Sv mice embryonic stem cell line.


METHODS
Cultured mouse ESCs were exposed to testosterone (T), dihydrotestosterone (DHT), or the antiandrogen nilutamide.


METHODS
Immunohistochemistry for androgen receptor (AR), quantitative real-time polymerase chain reaction analysis, cell colorimetric assays, and Western blot analysis.


RESULTS
Androgen receptor messenger RNA (mRNA) was first detected both in the inner cell mass from blastocysts and in undifferentiated ESCs. It increased stage-dependently during ESC differentiation. Although both T and DHT had marginal effects on AR mRNA expression level and cell growth in vitro, the nonsteroidal antiandrogen nilutamide significantly stimulated ESC growth and induced Akt expression. The enhancing effects of nilutamide on mouse ESCs indicated that the Akt pathway may be involved in nilutamide-promoted ESC growth.


CONCLUSIONS
These findings provide the first evidence of the existence of AR in ESCs. During differentiation, the expression level of AR was increased in a stage-dependent but not a ligand-dependent manner. Nilutamide promoted cell growth and increased Akt expression in ESCs.
Chang
Chih-Yang
CY
Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Hsuuw
Yan-Der
YD
Huang
Fu-Jen
FJ
Shyr
Chih-Rong
CR
Chang
Shiuh-Young
SY
Huang
Chiung-Kuei
CK
Kang
Hong-Yo
HY
Huang
Ko-En
KE
D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000008:administration & dosage*; D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D048289:Imidazolidines / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology
D000726:Androgen Antagonists; D000728:Androgens; D048289:Imidazolidines; D011941:Receptors, Adrenergic; D013196:Dihydrotestosterone; D013739:Testosterone; C021277:nilutamide