Harlow Christopher R, Rae Mick, Davidson Lindsay, Trackman Philip C, Hillier Stephen G
University of Edinburgh, Department of Reproductive and Developmental Sciences, Edinburgh, Scotland EH16 4SB, United Kingdom.
Endocrinology. 2003 Jan;144(1):154-62. doi: 10.1210/en.2002-220652.
Lysyl oxidase (LOX) catalyzes the final enzymatic reaction required for cross-linking of collagen and elastin fibers and therefore has a crucial role in regulating the formation and maintenance of extracellular matrix in the ovary. LOX mRNA is abundantly expressed in rat granulosa cells. To examine how regulation of LOX in the ovary might influence follicular development, we studied LOX mRNA expression and enzyme activity in rat granulosa cells from late preantral/early antral follicles in vitro. FSH dose dependently inhibited LOX mRNA and enzyme activity (50% reduction at 10 ng/ml) in vitro, and FSH action was mimicked by 8-bromo-cAMP, suggesting FSH action via elevation of cAMP. Dihydrotestosterone alone enhanced LOX mRNA and enzyme activity, but potentiated the effect of FSH, causing a further reduction. TGFbeta1 alone dose dependently enhanced LOX mRNA (5-fold increase at 10 ng/ml) and activity (1.5-fold increase). FSH dose dependently inhibited the increase in LOX mRNA and activity caused by TGFbeta1 (by up to 84% and 80%, respectively). Growth differentiation factor-9 (GDF-9) and activin A, at the same concentration as TGFbeta1 (10 ng/ml), stimulated LOX mRNA and activity within 6 h, although overall expression was higher at 48 h. All three factors when combined with FSH further reduced both mRNA and enzyme activity (by up to 60%) compared with FSH alone. These findings indicate control of LOX at endocrine, paracrine, and autocrine levels within the ovary and suggest coordinated regulation of ovarian extracellular matrix during follicular development, with FSH determining whether local factors act as stimulators or inhibitors of LOX.
赖氨酰氧化酶（LOX）催化胶原蛋白和弹性纤维交联所需的最后一步酶促反应，因此在调节卵巢细胞外基质的形成和维持中起着关键作用。LOX mRNA在大鼠颗粒细胞中大量表达。为了研究卵巢中LOX的调节如何影响卵泡发育，我们在体外研究了来自晚窦前/早窦卵泡的大鼠颗粒细胞中LOX mRNA的表达和酶活性。促卵泡激素（FSH）在体外剂量依赖性地抑制LOX mRNA和酶活性（10 ng/ml时降低50%），8-溴环磷酸腺苷（8-bromo-cAMP）可模拟FSH的作用，提示FSH通过升高环磷酸腺苷（cAMP）发挥作用。单独的双氢睾酮可增强LOX mRNA和酶活性，但增强了FSH的作用，导致进一步降低。单独的转化生长因子β1（TGFbeta1）剂量依赖性地增强LOX mRNA（10 ng/ml时增加5倍）和活性（增加1.5倍）。FSH剂量依赖性地抑制TGFbeta1引起的LOX mRNA和活性增加（分别高达84%和80%）。生长分化因子9（GDF-9）和激活素A在与TGFbeta1相同的浓度（10 ng/ml）下，在6小时内刺激LOX mRNA和活性，尽管在48小时时总体表达更高。与单独使用FSH相比，这三种因子与FSH联合使用时，mRNA和酶活性均进一步降低（高达60%）。这些发现表明卵巢内存在内分泌、旁分泌和自分泌水平对LOX的控制，并提示卵泡发育过程中卵巢细胞外基质的协调调节，FSH决定局部因子是作为LOX的刺激剂还是抑制剂。
