NCBI Summary:
This gene encodes a protein that contains a Ras association domain. Similar to its cattle and sheep counterparts, this gene is located near the prion gene. Two alternatively spliced transcripts encoding the same isoform have been reported. [provided by RefSeq, Jul 2008]
General function
Intracellular signaling cascade
Comment
Cellular localization
Cytoplasmic
Comment
Ovarian function
Comment
Expression regulated by
LH, Steroids
Comment
Ovarian localization
Granulosa
Comment
The absence of ER?results in altered gene expression in ovarian granulosa cells isolated from in vivo preovulatory follicles. Binder AK et al. Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER) ?is highly expressed in ovarian granulosa cells and mice lacking ER?(?RKO) are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and while informative, provides confounding results due to the heterogeneous cell types present including granulosa, theca and oocytes and exposure to in vitro conditions. Herein, we isolated preovulatory granulosa cells from WT and ER?null mice using laser capture microdissection to examine the genomic transcriptional response downstream of PMSG (mimicking FSH) and PMSG/hCG (mimicking LH) stimulation. This allows for a direct comparison of in vivo granulosa cells at the same stage of development from both WT and ER?null ovaries. ER?null granulosa cells showed altered expression of genes known to be regulated by FSH (Akap12 and Runx2) as well as not previously reported (Arnt2 and Pou5f1) in WT granulosa cells. Our analysis also identified 304 genes not previously associated with ER?in granulosa cells. LH responsive genes including Abcb1b and Fam110c show reduced expression in ER?null granulosa cells; however novel genes including Rassf2 and Megf10 were also identified as being downstream of LH signaling in granulosa cells. Collectively, our data suggests that granulosa cells from ER?null ovaries may not be appropriately differentiated and are unable to respond properly to gonadotropin stimulation.