Hirvonen-Santti Sirpa J, Sriraman Venkataraman, Anttonen Mikko, Savolainen Saija, Palvimo Jorma J, Heikinheimo Markku, Richards Joanne S, Jänne Olli A
Biomedicum Helsinki, Institute of Biomedicine (Physiology), University of Helsinki, P.O. Box 63, FIN-00014 Helsinki, Finland.
Endocrinology. 2004 May;145(5):2433-44. doi: 10.1210/en.2003-1328. Epub 2004 Jan 28.
Small nuclear RING finger protein (SNURF/RNF4) is a steroid receptor coregulator that is down-regulated in testicular germ cell cancer. In this work, we examined SNURF expression during murine fetal gonad development and postnatal ovarian folliculogenesis by in situ hybridization and immunohistochemical staining. SNURF mRNA was detectable in gonads of both sexes from embryonic 10.5 days post conception onward. SNURF protein localized to gonocytes and somatic Leydig and Sertoli cells of fetal testis and in oogonia and supporting cells of fetal ovary. In murine postnatal ovary, SNURF mRNA and protein were expressed throughout folliculogenesis, peaking in the oocytes of preantral follicles. Lower amounts of SNURF mRNA and protein were also present in granulosa cells of secondary, antral, and preovulatory follicles and in luteal glands. Exposure of immature female mice and rats to gonadotropin from pregnant mare serum and human chorionic gonadotropin did not change dramatically SNURF mRNA levels in ovary. SNURF mRNA expression was increased in ovaries of immature mice treated with diethylstilbestrol, an effect that was blocked by the pure antiestrogen ICI 182,780. SNURF protein was constitutively expressed in oocytes of hypophysectomized rats, and its content was augmented by estradiol in granulosa cells. In granulosa cell culture, SNURF mRNA accumulation was transiently increased by treatment with the LH agonists phorbol myristate and forskolin at 4 h after treatment and at 48 h in differentiated cells expressing markers of the preovulatory phenotype. These results suggest a role for SNURF in fetal germ cell development as well as in oocyte and granulosa cell maturation in an estrogen- and gonadotropin-regulated fashion.
小核环指蛋白（SNURF/RNF4）是一种类固醇受体共调节因子，在睾丸生殖细胞癌中表达下调。在本研究中，我们通过原位杂交和免疫组织化学染色检测了小鼠胎儿性腺发育和出生后卵巢卵泡发生过程中SNURF的表达。从胚胎受孕后10.5天起，两性性腺中均可检测到SNURF mRNA。SNURF蛋白定位于胎儿睾丸的生殖细胞、体细胞Leydig细胞和支持细胞以及胎儿卵巢的卵原细胞和支持细胞中。在小鼠出生后的卵巢中，SNURF mRNA和蛋白在整个卵泡发生过程中均有表达，在窦前卵泡的卵母细胞中达到峰值。次级卵泡、窦状卵泡和排卵前卵泡的颗粒细胞以及黄体中也存在少量的SNURF mRNA和蛋白。将未成熟雌性小鼠和大鼠暴露于孕马血清促性腺激素和人绒毛膜促性腺激素中，卵巢中SNURF mRNA水平没有显著变化。用己烯雌酚处理未成熟小鼠的卵巢后，SNURF mRNA表达增加，而这种作用被纯抗雌激素ICI 182,780阻断。SNURF蛋白在垂体切除大鼠的卵母细胞中组成性表达，其在颗粒细胞中的含量因雌二醇而增加。在颗粒细胞培养中，用LH激动剂佛波醇肉豆蔻酸酯和福斯高林处理后4小时以及在表达排卵前表型标志物的分化细胞中处理48小时后，SNURF mRNA积累短暂增加。这些结果表明，SNURF在胎儿生殖细胞发育以及雌激素和促性腺激素调节的卵母细胞和颗粒细胞成熟中发挥作用。
