Androgen activation of the folate receptor alpha gene through partial tethering of the androgen receptor by C/EBP alpha

作者：Sivakumaran Suneethi; Zhang Juan; Kelley Karen M M; Gonit Mesfin; Hao Hong; Ratnam Manohar^*

来源：Journal of Steroid Biochemistry and Molecular Biology, 2010, 122(5): 333-340.

DOI：10.1016/j.jsbmb.2010.08.008

• Folate receptor
• Folate
• C/EBP alpha
• Androgen receptor

The folate receptor a (FR alpha) is critical for normal embryonic and fetal development. The receptor has a relatively narrow tissue specificity which includes the visceral endoderm and the placenta and mediates delivery of folate, inadequacy of which results in termination of pregnancy or developmental defects. We have previously reported that the FR alpha gene is negatively and directly regulated by estrogen and positively but indirectly by progesterone and glucocorticoid. To further investigate hormonal control of this gene and in view of the growing evidence for the importance of the androgen receptor (AR) in endometrial and placental functions, we examined the response of the FR alpha gene to androgen. Here we demonstrate that the FR alpha gene is directly activated by androgen. The P4 promoter of the FR alpha gene is the target of hormone-dependent activation by the androgen receptor (AR) in a manner that is co-activator-dependent. The site of functional association of AR in the FR alpha gene maps to a 35 bp region occurring similar to 1500 bp upstream of the target promoter. The functional elements within this region are an androgen response element (ARE) half-site and a non-canonical C/EBP element that cooperate to recruit AR in a manner that is dependent on the DNA-bound C/EBP alpha Since the placenta is rich in C/EBP alpha, the findings underscore the multiplicity of mechanisms by which the FR alpha gene is under the exquisite control of steroid hormones.

• 出版日期2010-11