Herr D, Keck C, Tempfer C, Pietrowski Detlef
University Medical School, Freiburg, Germany.
Mol Reprod Dev. 2004 Dec;69(4):397-401. doi: 10.1002/mrd.20137.
The ovarian corpus luteum plays a critical role in reproduction being the primary source of circulating progesterone. After ovulation the corpus luteum is build by avascular granulosa lutein cells through rapid vascularization regulated by gonadotropic hormones. The present study was performed to investigate whether this process might be influenced by the human chorionic gonadotropin (hCG)-dependent expression of different tumor suppressor genes and hypoxia dependent transcription factors. RNA was isolated from cultured granulosa lutein cells, transcribed into cDNA, and the transcript level of following genes were determined: RB-1, VHL, NF-1, NF-2, Wt-1, p53, APC, and hypoxia inducible factor-1 (HIF-1), -2, and -3alpha. Additionally, the influence of hCG on the expression of VHL, p53, and HIf2alpha were investigated. We demonstrate that in human granulosa lutein cells the tumor suppressor genes RB-1, VHL, NF-1, NF-2, Wt-1, p53, and APC and the hypoxia dependent transcription factors HIF-1alpha, -2alpha, and -3alpha are expressed. In addition, we showed that hCG regulates the expression of p53, VHL, and HIF-2alpha. Our results indicate that hCG may determine the growth and development of the corpus luteum by mediating hypoxic and apoptotic pathways in human granulosa lutein cells.
卵巢黄体在生殖过程中起着关键作用,是循环孕酮的主要来源。排卵后,黄体由无血管的颗粒黄体细胞通过促性腺激素调节的快速血管生成而形成。本研究旨在探讨这一过程是否可能受到不同肿瘤抑制基因的人绒毛膜促性腺激素(hCG)依赖性表达和缺氧依赖性转录因子的影响。从培养的颗粒黄体细胞中分离RNA,转录成cDNA,并测定以下基因的转录水平:RB-1、VHL、NF-1、NF-2、Wt-1、p53、APC以及缺氧诱导因子-1(HIF-1)、-2和-3α。此外,还研究了hCG对VHL、p53和HIf2α表达的影响。我们证明,在人颗粒黄体细胞中,肿瘤抑制基因RB-1、VHL、NF-1、NF-2、Wt-1、p53和APC以及缺氧依赖性转录因子HIF-1α、-2α和-3α均有表达。此外,我们还表明hCG调节p53、VHL和HIF-2α的表达。我们的结果表明,hCG可能通过介导人颗粒黄体细胞中的缺氧和凋亡途径来决定黄体的生长和发育。