Androgenic and antiandrogenic effects and expression of androgen receptor in mouse embryonic stem cells

Abstract

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.

Design: Controlled laboratory study.

Setting: Academic university hospital.

Animal(s): Blastocysts from mice developed at the Institute for Cancer Research and 129/Sv mice embryonic stem cell line.

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

Main outcome measure(s): Immunohistochemistry for androgen receptor (AR), quantitative real-time polymerase chain reaction analysis, cell colorimetric assays, and Western blot analysis.

Result(s): 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.

Conclusion(s): 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.