College of Animal Science, Jilin University, 5333 Xian Road, Changchun, Jilin, 130062, China.
Reprod Biol Endocrinol. 2018 Mar 20;16(1):25. doi: 10.1186/s12958-018-0348-8.
Ovarian retinoid homeostasis plays an important role in the physiological function of the ovary. Retinol-binding protein 4 (RBP4) acts as the mediator for the systemic and intercellular transport of retinol and is heavily involved in cellular retinol influx, efflux, and exchange. However, the expression patterns and regulatory mechanisms of Rbp4 in the ovary remain unclear.
The expression pattern of ovarian Rbp4 was examined in immature mice during different developmental stages and in adult mice during different stages of the estrous cycle. The potential regulation and mechanisms of ovarian Rbp4 expression by estrogen and related gonadotropins in mouse ovaries were also investigated.
The present study demonstrated that the ovarian expression of Rbp4 remained constant before puberty and increased significantly in the peripubertal period. In adult female mice, the expression of Rbp4 increased at proestrus and peaked at estrus at both the mRNA and protein levels. The protein distribution of RBP4 was mainly localized in the granulosa cell and theca cell layer in follicles. In addition, the expression of Rbp4 was significantly induced by follicle-stimulating hormone (FSH) or FSH + luteinizing hormone (LH) in combination in immature mouse (3 weeks old) ovaries in vivo and in granulosa cells cultured in vitro, both at the mRNA and protein levels. In contrast, treatment with LH or 17β-estradiol did not exhibit any observable effects on ovarian Rbp4 expression. Transcription factors high-mobility group AT-hook 1 (HMGA1), steroidogenic factor 1 (SF-1), and liver receptor homolog 1 (LRH-1) (which have been previously shown to be involved in activation of Rbp4 transcription), also responded to FSH stimulation. In addition, H-89, an inhibitor of protein kinase A (PKA), and the depletion of HMGA1, SF-1, and LRH-1 by small interfering RNAs (siRNAs), resulted in a dramatic loss of the induction of Rbp4 expression by FSH at both the mRNA and protein levels.
These data indicate that the dynamic expression of Rbp4 is mainly regulated by FSH through the cAMP-PKA pathway, involving transcriptional factors HMGA1, SF-1, and LRH-1, in the mouse ovary during different stages of development and the estrous cycle.
卵巢视黄醇稳态在卵巢的生理功能中起着重要作用。视黄醇结合蛋白 4（RBP4）作为视黄醇的全身和细胞间转运的介质，大量参与细胞内视黄醇的流入、流出和交换。然而，Rbp4 在卵巢中的表达模式和调节机制尚不清楚。
在不同发育阶段的未成熟小鼠和不同动情周期阶段的成年小鼠中，检查了卵巢 Rbp4 的表达模式。还研究了雌激素和相关促性腺激素对小鼠卵巢中 Rbp4 表达的潜在调节和机制。
本研究表明，Rbp4 在青春期前的卵巢表达保持不变，在青春期前时期显著增加。在成年雌性小鼠中，Rbp4 的表达在发情前期增加，并在发情期达到 mRNA 和蛋白质水平的峰值。RBP4 的蛋白分布主要定位于卵泡中的颗粒细胞和膜细胞层。此外，在体内和体外培养的颗粒细胞中，FSH 或 FSH+促黄体生成素（LH）联合刺激均可显著诱导 3 周龄未成熟小鼠（3 周龄）卵巢和 Rbp4 的表达在 mRNA 和蛋白质水平上。相比之下，LH 或 17β-雌二醇处理对卵巢 Rbp4 表达没有任何可见的影响。转录因子高迁移率族 AT 盒 1（HMGA1）、类固醇生成因子 1（SF-1）和肝受体同系物 1（LRH-1）（先前已显示参与 Rbp4 转录的激活）也对 FSH 刺激有反应。此外，蛋白激酶 A（PKA）抑制剂 H-89 和通过小干扰 RNA（siRNA）耗尽 HMGA1、SF-1 和 LRH-1，导致 FSH 对 Rbp4 表达的诱导在 mRNA 和蛋白质水平上均显著丧失。
这些数据表明，Rbp4 的动态表达主要通过 FSH 通过 cAMP-PKA 途径调节，涉及转录因子 HMGA1、SF-1 和 LRH-1，在小鼠卵巢在不同的发育阶段和动情周期。
