INTRAOVARIAN REGULATORS INVOLVED IN HUNAN FOLLICULAR GROWTH AND DISEASE

卵巢内调节剂在卵泡生长中的重要性已得到越来越多的认识。激活素和卵泡抑素最初是从卵泡液中提纯为性腺蛋白，它调节脑下垂体前叶FSH的产生。然而，最近，人们的注意力集中在它们在卵巢中的自分泌/旁分泌作用上。我们的研究调查了当地对其生产的监管制度。激活素和FSH可刺激卵巢颗粒细胞产生卵泡抑素，环状AMP和PMA可诱导卵泡抑素mRNA的表达增加，提示PKA和PKC通路均参与卵泡抑素的产生。激活素不仅刺激卵泡生成素的产生，而且还刺激FSH受体的诱导，而这种对FSH受体的刺激作用又被卵泡素抑制。提示卵巢颗粒细胞存在激活素的局部调控系统。Midkine是Re…的产物近年来已有更多的天麻酸应答基因及其在卵泡液中的存在的报道。利用原位杂交技术，证明中期因子mRNA仅存在于卵巢颗粒细胞中。卵泡刺激素或维甲酸使培养的颗粒细胞中期因子基因表达增加。时程分析表明，8-溴-cAMP可模拟FSH的刺激作用，但不能模拟中期因子的刺激作用。这些结果表明颗粒细胞在卵泡刺激素和维甲酸的独立控制下产生中期因子。我们还报道了促性腺激素注射在卵泡膜细胞中表达的羰基还原酶。此外，我们还研究了用于研究人卵泡生长的实验系统。我们改进了人抑制素检测系统，并利用表达人FSH受体的CHO细胞建立了人FSH生物检测系统。我们的研究有助于阐明卵泡生长的局部调控机制，并有助于探索治疗人类卵巢疾病的独特诊断和治疗方法。较少

The significance of intraovarian regulators in follicular growth has become increasingly recognized. Activins and follistatins were initially purified from follicular fluid as gonadal protein which modulate FSH production by the anterior pituitary gland. Recently, however much of the attention centers on their autocrine/paracrine actions in the ovary. Our study investigated the local regulatory system of their production. The production of follistatin in ovarian granulosa cell culture was stimulated by activin and FSH.Cyclic AMP and PMA induced an increase of follistatin mRNA and the involvement of both the PKA and the PKC pathways in follistatin production was suggested. Activin stimulated not only follistatin production but also the induction of the FSH receptor, and this stimulatory effect on the FSH receptor in turn was inhibited by follistatin. Therefore, it was suggested that a local regulatory system of activin in the ovarian granulosa cells exists.Midkine is the product of a re … More tinoic acid responsive gene and it's existence in follicular fluid has been reported recently. Using the in situ hybridization technique, we proved that midkine mRNA exists exclusively in granulosa cells in the ovary. Midkine mRNA in cultured granulosa cells increased in the presence of FSH or retinoic acid. The time course analysis revealed that stimulatory effects of FSH were mimicked by 8-Br-cAMP but those of midkine were not mimicked. These results suggested that granulosa cells produce midkine under the independent control of FSH and retinoic acid.We also reported on carbonyl reductases which were expressed in ovarian theca cells by gonadotropin injection using the subtraction hybridization technique.Useful assay systems in the study of human follicular growth were also investigated. Human inhibin assay systems were improved and a human FSH bioassay system was established using CHO cells expressing human FSH receptors.Our study assists in clarifying the local regulatory mechanisms in follicular growth and helps to investigate the unique diagnostic and therapeutic methods in the treatment of human ovarian disorder. Less