The Androgen and Progesterone Receptors Regulate Distinct Gene Networks and Cellular Functions in Decidualizing Endometrium

摘要: Progesterone is indispensable for differentiation of human endometrial stromal cells (HESCs) into decidual cells, a process that critically controls embryo implantation. We now show an important role androgen receptor (AR) signaling in this process. Decreased posttranslational modification the AR by small ubiquitin-like modifier (SUMO)-1 decidualizing accounted increased responsiveness to androgen. By combining interfering RNA technology with genome-wide expression profiling, we found and progesterone (PR) regulate distinct gene networks. Ingenuity pathway analysis implicated preponderance AR-induced genes cytoskeletal organization cell motility, whereas AR-repressed suggested involvement cycle regulation. Functionally, depletion prevented differentiation-dependent stress fiber formation promoted motility proliferation cells. In comparison, PR perturbed many more genes, underscoring importance nuclear diverse cellular functions. However, several PR-dependent encode intermediates, knockdown PR, but not AR, compromised activation WNT/β-catenin, TGFβ/SMAD, signal transducer activator transcription (STAT) pathways Thus, nonredundant function HESCs, centered on regulation, implies androgens modulating fetal-maternal interactions. Moreover, regulates HESC differentiation, at least part, reprogramming growth factor cytokine transduction.