Choi Yuri, Lee Okto, Ryu Kiyoung, Roh Jaesook
Laboratory of Reproductive Endocrinology, Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul 04763, Republic of Korea.
Department of Obstetrics & Gynecology, College of Medicine, Hanyang University, Guri-si 11923, Republic of Korea.
Biomedicines. 2023 Dec 27;12(1):71. doi: 10.3390/biomedicines12010071.
Previous in vivo and in vitro studies have demonstrated a dramatic up-regulation of () in rat preovulatory granulosa cells (GCs) after LH/hCG treatment and its role in regulating expression during the luteal shift in steroidogenesis. In this study, we examined whether also mediates the LH-induced repression of expression in primary rat preovulatory GCs. In response to LH treatment of GCs in vitro, expression declined to less than half of its initial value by 1 h, remaining low for 24 h of culture. Overexpression of decreased basal and -induced expressions and increased progesterone secretion. Reduction of endogenous by siRNA elevated basal expression but did not affect LH-stimulated progesterone production. Overexpression of also significantly attenuated -induced promoter activity. On the other hand, mutation of the conserved Sp1/Klf binding motif in the promoter revealed that this motif is not required for -mediated repression. Taken together, these data indicate that the gene may be one of the downstream targets of , which is induced by LH in preovulatory GCs. This information may help in identifying potential targets for preventing the molecular changes occurring in hyperandrogenic disorders.
先前的体内和体外研究表明，促黄体生成素/人绒毛膜促性腺激素（LH/hCG）处理后，大鼠排卵前颗粒细胞（GCs）中的（）显著上调，并且其在黄体期类固醇生成转变过程中调节（）表达方面发挥作用。在本研究中，我们检测了（）是否也介导LH诱导的原代大鼠排卵前GCs中（）表达的抑制。体外对GCs进行LH处理后，（）表达在1小时内降至初始值的一半以下，并在24小时培养期间保持较低水平。（）的过表达降低了基础和（）诱导的（）表达，并增加了孕酮分泌。通过小干扰RNA（siRNA）降低内源性（）可提高基础（）表达，但不影响LH刺激的孕酮产生。（）的过表达也显著减弱了（）诱导的（）启动子活性。另一方面，启动子中保守的Sp1/Klf结合基序的突变表明，该基序对于（）介导的抑制作用并非必需。综上所述，这些数据表明（）基因可能是（）的下游靶点之一，（）在排卵前GCs中由LH诱导产生。这一信息可能有助于识别预防高雄激素血症相关疾病中发生的分子变化的潜在靶点。
