A stimulatory role of cyclic adenosine 3',5'-monophosphate in follicle-stimulating hormone-activated mitogen-activated protein kinase signaling pathway in rat ovarian granulosa cells.
A stimulatory role of cyclic adenosine 3',5'-monophosphate in follicle-stimulating hormone-activated mitogen-activated protein kinase signaling pathway in rat ovarian granulosa cells.
复制标题
DOI：
10.1210/endo.137.3.8603610
复制
发表时间：
1996-03
期刊：
影响因子：
4.8
通讯作者：
S. Das;E. Maizels;D. Demanno;E. S. Clair;S. Adam;M. Hunzicker-Dunn
中科院分区：
文献类型：
--
作者：
S. Das;E. Maizels;D. Demanno;E. S. Clair;S. Adam;M. Hunzicker-Dunn
FSH通过cAMP依赖性机制促进卵巢卵泡颗粒细胞的分化。基于存在一个突出的磷脂/二油酸甘油酯/Ca 2 +-独立的髓鞘碱性蛋白激酶活性的可溶性提取物的增殖未成熟的大鼠颗粒细胞，我们确定这种活动是否是由于有丝分裂原活化蛋白激酶（MAPKs），一个无处不在的家庭的髓鞘碱性蛋白激酶，以及是否FSH急性调节的MAPKs在大鼠颗粒细胞。从用17 β-雌二醇处理以促进颗粒细胞增殖的未成熟大鼠卵巢中的大腔前卵泡获得颗粒细胞。在含有10 nM 17 β-雌二醇的无血清培养基中过夜培养的颗粒细胞暴露于50 ng/ml FSH 10 min可促进MAPK活性增加2- 5倍。FSH的作用被毛喉素模拟，并被cAMP依赖性蛋白激酶抑制剂H89抑制，但不被酪氨酸激酶抑制剂Ag-18抑制。FSH还促进了90 kDa核糖体S6蛋白激酶的磷酸化和外源性S6蛋白的磷酸化。这些结果表明FSH启动颗粒细胞分化的cAMP导向途径包括MAPK的激活。
FSH promotes the differentiation of ovarian follicular granulosa cells via a cAMP-dependent mechanism. Based upon the presence of a prominent phospholipid/diolein/Ca2+-independent myelin basic protein kinase activity in soluble extracts of proliferating immature rat granulosa cells, we determine whether this activity was attributable to the mitogen-activated protein kinases (MAPKs), one of the ubiquitous families of myelin basic protein kinases, and whether FSH acutely regulated the MAPKs in rat granulosa cells. Granulosa cells were obtained from large preantral follicles in ovaries of immature rats treated with 17beta-estradiol to promote granulosa cell proliferation. Exposure of granulosa cells, cultured overnight in serum-free medium containing 10 nM 17beta- estradiol, to 50 ng/ml FSH for 10 min promoted a 2- to 5- fold increase in MAPK activity. The effects of FSH were mimicked by forskolin and inhibited by the inhibitor of cAMP- dependent protein kinase H89, but were not inhibited by the tyrosine kinase inhibitor Ag-18. FSH also promoted increased phosphorylation of the 90-kDa ribosomal S6 protein kinase and phosphorylation of exogenous S6 protein. These results suggest that the cAMP-directed pathway by which FSH initiates granulosa cell differentiation includes activation of MAPKs.