GnRH binds its cognate G protein-coupled GnRH receptor (GnRHR) located on 
pituitary gonadotropes and drives expression of gonadotropin hormones. There are 
two gonadotropin hormones, comprised of a common alpha- and hormone-specific 
beta-subunit, which are required for gonadal function. Recently we identified 
that Fanconi anemia a (Fanca), a DNA damage repair gene, is differentially 
expressed within the LbetaT2 gonadotrope cell line in response to stimulation 
with GnRH. FANCA is mutated in more than 60% of cases of Fanconi anemia (FA), a 
rare genetically heterogeneous autosomal recessive disorder characterized by 
bone marrow failure, endocrine tissue cancer susceptibility, and infertility. 
Here we show that induction of FANCA protein is mediated by the GnRHR and that 
the protein constitutively adopts a nucleocytoplasmic intracellular distribution 
pattern. Using inhibitors to block nuclear import and export and a GnRHR 
antagonist, we demonstrated that GnRH induces nuclear accumulation of FANCA and 
green fluorescent protein (GFP)-FANCA before exporting back to the cytoplasm 
using the nuclear export receptor CRM1. Using FANCA point mutations that locate 
GFP-FANCA to the cytoplasm (H1110P) or functionally uncouple GFP-FANCA (Q1128E) 
from the wild-type nucleocytoplasmic distribution pattern, we demonstrated that 
wild-type FANCA was required for GnRH-induced activation of gonadotrope cell 
markers. Cotransfection of H1110P and Q1128E blocked GnRH activation of the 
alphaGsu and GnRHR but not the beta-subunit gene promoters. We conclude that 
nucleocytoplasmic shuttling of FANCA is required for GnRH transduction of the 
alphaGSU and GnRHR gene promoters and propose that FANCA functions as a 
GnRH-induced signal transducer.