Key Laboratory of Animal Resistance Research, College of Life Science, Shandong Normal University, Ji'nan, Shandong, China.
Clinical Laboratory, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medicine Science, Ji'nan, Shandong, China.
Biol Reprod. 2017 Jan 1;97(6):862-872. doi: 10.1093/biolre/iox134.
The membrane proteins, low-density lipoprotein receptor (LDLR) and scavenger receptor class B member 1 (SR-BI, gene name Scarb1), are lipoprotein receptors that play central roles in lipoprotein metabolism. Cholesterol bound in high-density lipoprotein (HDL) and LDL is transported into cells mainly by SR-BI and LDLR. The relative contribution of LDL and HDL to the steroidogenic cholesterol pool varies among species and may vary among tissues within one species. To investigate which of these pathways is more important in the supply of cholesterol in mouse ovary, we utilized immunohistochemistry, western blotting, RNAi, and RT-PCR as well as Ldlr-/- mice to explore the uptake of HDL and LDL in the ovary. Our data demonstrate that both SR-BI and LDLR are present in the interstitial cells, thecal cells, and corpora lutea (CLs), and their expression fluctuates with the development of follicles and CLs. The intracellular cholesterol concentration was significantly decreased when Ldlr or Scarb1 was silenced in luteal cells. Furthermore, Ldlr-/- mice had lower progesterone and estrogen levels compared to wild-type mice, and when Ldlr-/- mice were treated with the inhibitor of de novo cholesterol synthesis, lovastatin, serum progesterone, and estrogen concentrations were further reduced. These results demonstrate that both LDLR and SR-BI play important roles in importing cholesterol and that both HDL and LDL are crucial in steroidogenesis in mouse ovaries.
膜蛋白，低密度脂蛋白受体（LDLR）和清道夫受体 B 类成员 1（SR-BI，基因名称 Scarb1），是脂蛋白受体，在脂蛋白代谢中发挥核心作用。载脂蛋白结合的胆固醇高密度脂蛋白（HDL）和 LDL 主要通过 SR-BI 和 LDLR 进入细胞。LDL 和 HDL 对类固醇生成胆固醇池的相对贡献因物种而异，在同一物种的不同组织中也可能有所不同。为了研究这些途径中哪一种在供应小鼠卵巢中的胆固醇中更为重要，我们利用免疫组织化学、Western blot、RNAi 和 RT-PCR 以及 Ldlr-/- 小鼠来研究 HDL 和 LDL 在卵巢中的摄取。我们的数据表明，SR-BI 和 LDLR 均存在于间质细胞、卵泡膜细胞和黄体（CL）中，其表达随卵泡和 CL 的发育而波动。当黄体细胞中沉默 Ldlr 或 Scarb1 时，细胞内胆固醇浓度显着降低。此外，与野生型小鼠相比，Ldlr-/- 小鼠的孕激素和雌激素水平较低，当 Ldlr-/- 小鼠用从头合成胆固醇抑制剂 lovastatin 治疗时，血清孕激素和雌激素浓度进一步降低。这些结果表明，LDLR 和 SR-BI 均在导入胆固醇中发挥重要作用，HDL 和 LDL 均在小鼠卵巢的类固醇生成中至关重要。
