Feijing Zhou, Sun Zhimin, Cheng Luyao, Dong Yuezhi
Reproductive Medicine Centre, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Reproductive Medicine Centre, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Lab Invest. 2025 Feb;105(2):102169. doi: 10.1016/j.labinv.2024.102169. Epub 2024 Nov 2.
Leptin (LEP) is implicated in the pathogenesis of polycystic ovary syndrome (PCOS). This study investigates the mechanism of LEP in PCOS. The baseline information of 80 PCOS patients and matched controls was analyzed, with serum and follicular fluid (FF) LEP and LEP receptor (LEPR) levels, telomerase activity, and relative telomere length (TL) measured. The correlation of FF LEP with telomerase activity and TL was analyzed. The viability and apoptosis of KGN cells (the ovarian granulosa cells) treated with gradient LEP were assessed. LEP-LEPR interaction was examined. LEPR, v-myc avian myelocytomatosis viral oncogene homolog (c-MYC), and telomerase reverse transcriptase (TERT) levels and c-MYC protein expression in the TERT promoter region were determined. Nuclear c-MYC translocation was detected. LEP was upregulated in sera and FF of PCOS patients. FF LEP positively correlated with telomerase activity and TL. Low-concentration LEP facilitated KGN cell proliferation, and high-concentration LEP dose-dependently suppressed cell proliferation, promoted apoptosis, upregulated LEPR, and increased telomerase activity and relative TL. LEP-LEPR interaction upregulated c-MYC and facilitated its nuclear accumulation. c-MYC enrichment in the TERT promoter region upregulated TERT, altering telomerase activity and TL and inducing cell apoptosis. Briefly, LEP/LEPR activates c-MYC, modulates TERT expression, and increases telomerase activity and TL, thus inducing ovarian granulosa cell apoptosis and participating in PCOS.
瘦素（LEP）与多囊卵巢综合征（PCOS）的发病机制有关。本研究探讨LEP在PCOS中的作用机制。分析了80例PCOS患者及匹配对照的基线信息，检测血清和卵泡液（FF）中的LEP和LEP受体（LEPR）水平、端粒酶活性及相对端粒长度（TL）。分析FF LEP与端粒酶活性和TL的相关性。评估用梯度LEP处理的KGN细胞（卵巢颗粒细胞）的活力和凋亡情况。检测LEP-LEPR相互作用。测定LEPR、v-myc禽成髓细胞瘤病毒癌基因同源物（c-MYC）和端粒酶逆转录酶（TERT）水平以及TERT启动子区域的c-MYC蛋白表达。检测核c-MYC易位情况。PCOS患者血清和FF中的LEP上调。FF LEP与端粒酶活性和TL呈正相关。低浓度LEP促进KGN细胞增殖，高浓度LEP则剂量依赖性地抑制细胞增殖、促进凋亡、上调LEPR，并增加端粒酶活性和相对TL。LEP-LEPR相互作用上调c-MYC并促进其核内积累。c-MYC在TERT启动子区域的富集上调TERT，改变端粒酶活性和TL并诱导细胞凋亡。简而言之，LEP/LEPR激活c-MYC，调节TERT表达，增加端粒酶活性和TL，从而诱导卵巢颗粒细胞凋亡并参与PCOS的发生。
