PL 40. Estrogen receptor alpha in mouse testis: A lesson from Leydig cell-specific and whole body estrogen receptor alpha knockout mice

The function of estrogen receptors (ERs) in reproduction has been well characterized in the female, but not well clarified in the male. To date, two ER subtypes, ERα and ERβ have been identified in mammals. In mouse testis, ERα has known to be expressed in Leydig cells and peritubular cells, but its role in Leydig cells is ambiguous up to present. In transgenic mouse model, ERα knockout resulted in male infertility largely due to the spermatogenic defect. Taking into account that ERα is expressed in the pituitary, whether spermatogenic defect was from Leydig cell specific or brain is unclear. In male mice lacking in ERα in Leydig cell (ERαf/f Cyp17iCre) spermatogenesis was normal but the fertility was decreased at 12 months. In ERαKO mouse testis was heavier than that of the WT at 2 months of age and seminiferous tubules were dilated. At 5 months of age, testis weight became decreased below the WT level and seminiferous epithelium showed an atrophy. In contrst, ERαf/f Cyp17iCre mouse testis showed normal seminiferous histology through 3-16 months of age. Serum testosterone levels of ERαKO male mice were significantly higher than those of WT through 2 - 5 months of age. In ERαf/f Cyp17iCre male mice, testosterone levels were not different until 12 months but significantly increased at 16 months of age. In ERαKO mouse testis StAR and 17βHSD3 mRNA levels were significantly higher than those of WT at 3 months of age. In ERαf/f Cyp17iCre mouse testis StAR mRNA levels were significantly higher than WT through 3 - 16 months of age, 17β-HSD3 mRNA levels were significantly higher at 12 months of age, and LHR mRNA levels were significantly higher at 16 months of age. In conclusion, whole body ERα KO resulted in spermatogenic defect largely due to pituitary dysfunction. ERα in Leydig cells may negatively affects steroidogenesis in aging male.