S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as IP3 receptor- binding protein released with IP3 (IRBIT), regulates IP3-induced Ca2+ release in the cytoplasm of cells and, therefore, is likely to be an important gene regulating various biological processes in the oviduct of chickens. However, the identification of the AHCYL1 gene in chickens has not been investigated. Therefore, the objectives of this study were to examine the tissue- and cell-specific expression of AHCYL1 gene in chicken organs, especially in reproductive organ, and determine functional actions of AHCYL1 in chicken oviduct development via estrogen. The results indicated that AHCYL1 mRNA is expressed in chicken reproductive organs and DES(diethylstilbesterol, a synthetic estrogen agonist) stimulates the cell specific expression of AHCYL1 in immature chicken oviduct. These results suggest that AHCYL1 is a novel estrogen-stimulated gene associated with development of the chicken oviduct. Next, in the present study, we show that inhibition of Erk1/2 can block DES-induced AHCYL1 expression. Also, we found that knockdown of AHCYL1 expression down-regulates expression of oviduct specific genes and AHCYL1 expression is regulated at the post-transcriptional level by specific miRNAs. These results strongly suggest that estrogen-mediated AHCYL1 gene expression plays a crucial role in growth, differentiation and function of the hen oviduct. Also, our results will be useful for understanding the fundamental mechanism(s) of estrogen action responsible for development of hen oviduct. This research was funded by the World Class University (WCU) program (R31-10056), Basic Science Research Program (2010-0013078) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology and by the Next-Generation BioGreen 21 Program (No.PJ008142), Rural Development Administration, Republic of Korea.