Expression and function of PAIRBP1 within gonadotropin-primed immature rat ovaries: PAIRBP1 regulation of granulosa and luteal cell viability
Expression and function of PAIRBP1 within gonadotropin-primed immature rat ovaries: PAIRBP1 regulation of granulosa and luteal cell viability
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DOI：
10.1095/biolreprod.105.041061
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发表时间：
2005-08-01
影响因子：
3.6
通讯作者：
Wehling, M
中科院分区：
文献类型：
--
作者：
Peluso, JJ;Pappalardo, A;Wehling, M
蛋白PAIRBP 1，最初被称为RDA 288，参与介导孕酮（P4）在自发永生化颗粒细胞（SIGCs）中的抗凋亡作用。本研究旨在评估PAIRBP 1在未成熟大鼠卵巢内不同类型细胞中的表达和功能。蛋白质印迹分析检测PAIRBP 1未成熟大鼠卵巢的全细胞裂解物。马促性腺激素（eCG）诱导卵巢PAIRBP 1水平增加3倍。此外，在eCG后48小时给予人绒毛膜促性腺激素（hCG），可维持这些升高的水平长达4天。免疫组化分析证实了这一点，并进一步表明，间质，卵泡膜，和表面上皮细胞也表达PAIRRP 1。在这些细胞中的PAIRBP 1水平不受促性腺激素处理的影响。相比之下，eCG刺激PAIRBP 1在发育卵泡的颗粒细胞内的增加。用hCG处理诱导排卵并最终形成黄体（CL）。在黄体细胞内也观察到高水平的PAIRBP 1表达。免疫细胞化学研究显示，一些PAIRBP 1定位于这些细胞的细胞外表面的生活，nonpermeabilized颗粒和黄体细胞。PAIRBP 1在细胞外表面的存在与PAIRBP 1抗体减弱P4在颗粒细胞和黄体细胞中的抗凋亡作用的观察结果一致。尽管PAIRBP 1抗体减弱了P4的作用，但它并没有降低细胞特异性结合H-3-P4的能力。用PAIRBP 1抗体进行免疫沉淀拉下膜P4结合蛋白，称为孕酮受体膜复合物-1（PGRMC 1;大鼠同源物登录号AJ 005837）。总之，这些研究结果表明，促性腺激素调节颗粒细胞和黄体细胞中PAIRBP 1的表达，PAIRBP 1在介导这些卵巢细胞类型中的P4 s抗凋亡作用中起着重要作用。PAIRBP 1的确切作用机制仍有待阐明，但它可能涉及与PGRMC 1的相互作用。
The protein PAIRBP1, which was initially referred to as RDA288, is involved in mediating the antiapoptotic action of progesterone (P4) in spontaneously immortalized granulosa cells (SIGCs). The present studies were designed to assess the expression and function of PAIRBP1 in the different cell types within the immature rat ovary. Western blot analysis detected PAIRBP1 within whole-cell lysates of immature rat ovaries. Equine gonadotropin (eCG) induced a 3-fold increase in ovarian levels of PAIRBP1. Moreover, human chorionic gonadotropin (hCG), given 48 h after eCG, maintained these elevated levels for up to 4 days. Immunohistochemical analysis confirmed this and further demonstrated that interstitial, thecal, and surface epithelial cells also expressed PAIRRP1. The level of PAIRBP1 in these cells was not influenced by gonadotropin treatment. In contrast, eCG stimulated an increase in PAIRBP1 within the granulosa cells of the developing follicles. Treatment with hCG induced ovulation and ultimately the formation of corpora lutea (CL). High levels of PAIRBP1 expression were also observed within the luteal cells. Immunocytochemical studies on living, nonpermeabilized granulosa and luteal cells revealed that some PAIRBP1 localized to the extracellular surface of these cells. The presence of PAIRBP1 on the extracellular surface was consistent with the observation that an antibody to PAIRBP1 attenuated P4's antiapoptotic action in both granulosa and luteal cells. Although the PAIRBP1 antibody attenuated P4's action, it did not reduce the capacity of cells to specifically bind H-3-P4. Immunoprecipitation with the PAIRBP1 antibody pulled down the membrane P4 binding protein known as progesterone receptor membrane complex-1 (PGRMC1; rat homolog accession number AJ005837). Taken together, these findings suggest that gonadotropins regulate the expression of PAIRBP1 in granulosa and luteal cells and that PAIRBP1 plays an important role in mediating P4s antiapoptotic action in these ovarian cell types. The exact mechanism of PAIRBP1's action remains to be elucidated, but it may involve an interaction with PGRMC1.