| The epididymis is a highly segmented organ that displays regionalized functions and gene expression. The initial segment has unique characteristics, including a functional dependence on the luminal contents that reach the epididymis via the rete testis and efferent ducts. Several genes found within the initial segment are dependent upon luminal testicular factors for their expression, including mRNA IV of the γ-glutamyl transpeptidase (GGT) gene. GGT mRNA IV is highly expressed in the principal cells of the initial segment, particularly zone 1a. Fibroblast growth factor-2 (FGF-2), acting through an FGF receptor and downstream signaling pathways, has been hypothesized to regulate GGT promoter IV by the PEA3 transcription factor. Evaluation of GGT promoter IV by in vivo electroporation demonstrated the importance of three PEA3 sites within 530 by upstream of the transcriptional start site, in addition to revealing negative-regulatory elements. These studies show that the principal cells in the initial segment express FGFR-1 IIIc and FGF-4 and -8 are in rete testis fluid. In addition, the nuclei of principal cells express phospho-ERK (P-ERK) and PEA3 in a segmental fashion, with the highest levels in zone 1a. The phosphorylation status of ERK and PEA3 protein levels are dependent upon luminal testicular factors, suggesting one mechanism by which FGF-2 could regulate GGT promoter IV. The results from these studies provide additional information regarding the importance of luminal testicular factors in regulating initial segment functions. |
