Parrott J A, Skinner M K
Reproductive Endocrinology Center, University of California, San Francisco 94143-0556, USA.
Endocrinology. 1998 May;139(5):2240-5. doi: 10.1210/endo.139.5.6018.
Interactions between mesenchymal-derived thecal cells and epithelial-derived granulosa cells are essential for follicular development in the ovary. These mesenchymal-epithelial cell interactions are in part mediated by keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and Kit ligand (KL). This study investigates the hypothesis that thecal cell-derived growth factors (e.g. KGF and HGF) regulate granulosa cell function, and granulosa cell-derived growth factors (e.g. KL) regulate thecal cell function. Gonadotropin regulation of this cell-cell interaction is also examined. Sensitive quantitative RT-PCR assays were used to analyze gene expression of KGF, HGF, and KL in the ovary. Thecal cell-derived KGF and HGF stimulated KL expression in bovine granulosa cells. Granulosa cell-derived KL stimulated KGF and HGF expression in bovine thecal cells. These results suggest that thecal and granulosa cells interact in a positive feedback loop mediated by KGF, HGF, and KL. Previous studies have suggested that gonadotropins (i.e. FSH and LH) regulate locally produced growth factor expression in the ovary. Treatment of bovine granulosa cells with FSH and hCG (a LH agonist) directly stimulated KL expression. The LH agonist hCG was also found to stimulate both KGF and HGF expression in thecal cells. The actions of gonadotropins on follicular development may in part be indirectly regulated by KL, KGF, and HGF expression. A novel positive feedback loop was identified between thecal cells and granulosa cells that is mediated by KL, KGF, and HGF. Thecal cell-derived KGF and HGF can stimulate granulosa cell-derived KL expression, and KL, in turn, can stimulate thecal cell-derived KGF and HGF expression. Combined observations support the hypothesis that mesenchymal-epithelial cell interactions between thecal and granulosa cells can play a significant role during ovarian follicular development and mediate gonadotropin actions.
间充质来源的卵泡膜细胞与上皮来源的颗粒细胞之间的相互作用对于卵巢中的卵泡发育至关重要。这些间充质-上皮细胞相互作用部分由角质形成细胞生长因子（KGF）、肝细胞生长因子（HGF）和Kit配体（KL）介导。本研究探讨了以下假设：卵泡膜细胞衍生的生长因子（如KGF和HGF）调节颗粒细胞功能，而颗粒细胞衍生的生长因子（如KL）调节卵泡膜细胞功能。还研究了促性腺激素对这种细胞间相互作用的调节。使用灵敏的定量RT-PCR测定法分析卵巢中KGF、HGF和KL的基因表达。卵泡膜细胞衍生的KGF和HGF刺激牛颗粒细胞中KL的表达。颗粒细胞衍生的KL刺激牛卵泡膜细胞中KGF和HGF的表达。这些结果表明，卵泡膜细胞和颗粒细胞在由KGF、HGF和KL介导的正反馈回路中相互作用。先前的研究表明，促性腺激素（即FSH和LH）调节卵巢中局部产生的生长因子表达。用FSH和hCG（一种LH激动剂）处理牛颗粒细胞直接刺激KL表达。还发现LH激动剂hCG刺激卵泡膜细胞中KGF和HGF的表达。促性腺激素对卵泡发育的作用可能部分由KL、KGF和HGF的表达间接调节。在卵泡膜细胞和颗粒细胞之间鉴定出一种由KL、KGF和HGF介导的新型正反馈回路。卵泡膜细胞衍生的KGF和HGF可刺激颗粒细胞衍生的KL表达，而KL反过来又可刺激卵泡膜细胞衍生的KGF和HGF表达。综合观察结果支持以下假设：卵泡膜细胞和颗粒细胞之间的间充质-上皮细胞相互作用在卵巢卵泡发育过程中可发挥重要作用并介导促性腺激素的作用。
