Huang A-Mei, Rudelius Martina, Sharan Shikha, McAllister Jan M, Raffeld Mark, Christenson Lane K, Sterneck Esta
Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
PLoS One. 2007 Dec 19;2(12):e1334. doi: 10.1371/journal.pone.0001334.
The CCAAT/enhancer binding protein (CEBP) family of transcription factors includes five genes. In the ovary, both Cebpa and Cebpb are essential for granulosa cell function. In this study we have explored the role of the Cebpd gene in ovarian physiology by expression and functional studies. Here we report that Cebpd (C/EBPdelta) is expressed in the mouse ovary in a highly restricted temporal and spatial pattern. In response to luteinizing hormone (LH/hCG), CEBPD expression is transiently induced in interstitial cells and in theca cells of follicles from the primary to pre-ovulatory stage, and overlaps in part with expression of the alpha-smooth muscle actin protein. Efficient down-regulation of CEBPD was dependent on a functional Cebpb gene. Proliferating human theca cells in culture also express Cebpd. Cells from patients with polycystic ovarian syndrome (PCOS) exhibited higher Cebpd expression levels. However, deletion of Cebpd in mice had no overt effect on ovarian physiology and reproductive function. Very little is known at present about the molecular mechanisms underlying theca/interstitial cell functions. The expression pattern of CEBPD reported here identifies a novel functional unit of mouse theca cells of primary through tertiary follicles responding to LH/hCG together with a subset of interstitial cells. This acute stimulation of CEBPD expression may be exploited to further characterize the hormonal regulation and function of theca and interstitial cells.
CCAAT/增强子结合蛋白(CEBP)转录因子家族包含五个基因。在卵巢中,Cebpa和Cebpb对颗粒细胞功能至关重要。在本研究中,我们通过表达和功能研究探索了Cebpd基因在卵巢生理学中的作用。在此我们报告,Cebpd(C/EBPδ)在小鼠卵巢中以高度受限的时空模式表达。响应促黄体生成素(LH/hCG),CEBPD表达在间质细胞和从初级卵泡到排卵前卵泡的卵泡膜细胞中被短暂诱导,并且部分与α-平滑肌肌动蛋白的表达重叠。CEBPD的有效下调依赖于功能性Cebpb基因。培养中的增殖人卵泡膜细胞也表达Cebpd。多囊卵巢综合征(PCOS)患者的细胞表现出更高的Cebpd表达水平。然而,小鼠中Cebpd的缺失对卵巢生理学和生殖功能没有明显影响。目前对于卵泡膜/间质细胞功能的分子机制知之甚少。此处报道的CEBPD表达模式确定了从小鼠初级卵泡到三级卵泡的卵泡膜细胞与一部分间质细胞一起对LH/hCG作出反应的一个新的功能单位。CEBPD表达的这种急性刺激可用于进一步表征卵泡膜细胞和间质细胞的激素调节及功能。