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Aquaporin 5 is regulated by estrogen and LH in mouse Leydig cells and is involved in steroidogenesis
Water channel proteins, aquaporins (AQPs) contribute to transepithelial water movement in many tissues. To date, 13 mammalian AQPs have been identified. Of these, AQP5 plays an important role in the fluid homeostasis and cell volume control in epithelial cells. In an effort to understand the role of AQP5 in testis, we investigated the expression of AQP5 in developing mouse testis, its regulation by estrogen and LH, and the change of steroidogenesis by AQP5 knockdown. Testes and Leydig cells were isolated from male mice at postnatal day (PND) 1, 7, 14, 28, and 56 and estrogen receptor alpha knockout (ERαKO) mice. In mouse testis, AQP5 immunoreactivity was negligible by PND 14. From PND 28 onward, AQP5 immunoreactivity was found in Leydig cells. In ERαKO mouse Leydig cells, AQP5 mRNA level was significantly lower than wild type. In primary adult Leydig cell culture, the expression of AQP5 mRNA was increased by 17β-estradiol (E2) and human chorionic gonadotropin (hCG), but was not changed in ERαKO Leydig cells. Moreover, the expression of AQP5 mRNA was increased by E2 and ERα-selective agonist PPT, but was not changed by ERβ-selective agonist DPN in primary Leydig cells and mLTC-1. In silico analysis and chromatin immunoprecipitation (ChIP) assay revealed that there are putative estrogen response elements (EREs) and cAMP response elements (CRE) in AQP5 promoter region. Testosterone secretion and steroidogenic pathway genes (StAR, Cyp11a1, Cyp17a1, and 3β-HSD6) expression were decreased by AQP5 siRNA in primary Leydig cells. In conclusion, AQP5 expression was coupled with functional differentiation of adult Leydig cells. AQP5 may play an important role in the fluid homeostasis and cell volume control during development of adult Leydig cells. The expression of AQP5 in Leydig cells could be regulated by ERα and LH signaling and AQP5 may be involved in steroidogenesis.
