Role of PCSK5 expression in mouse ovarian follicle development: identification of the inhibin α- and β-subunits as candidate substrates.
Role of PCSK5 expression in mouse ovarian follicle development: identification of the inhibin α- and β-subunits as candidate substrates.
复制标题
DOI：
10.1371/journal.pone.0017348
复制
发表时间：
2011-03-08
期刊：
影响因子：
3.7
通讯作者：
Woodruff TK
中科院分区：
文献类型：
--
作者：
Antenos M;Lei L;Xu M;Malipatil A;Kiesewetter S;Woodruff TK
抑制素和激活素是属于转化生长因子-β (TGFβ) 超家族的必需二聚体糖蛋白。抑制素是 α 和 β 亚基的异二聚体，而激活素是 β 亚基的同二聚体。抑制素的产生在生殖周期中受到调节，并且需要加工前配体以产生成熟的激素。弗林蛋白酶是一种类似枯草杆菌蛋白酶的前蛋白转化酶（原转化酶），在前体蛋白通过分泌途径和/或细胞表面的过程中，通过在碱性位点进行切割来激活前体蛋白。我们假设弗林蛋白酶样原转化酶是卵巢内抑制素 α 和 β 亚基加工的中心调节因子。我们通过实时定量 RT-PCR 分析了发育中的小鼠卵巢中弗林蛋白酶原、PCSK5、PCSK6 和 PCSK7 的表达。数据显示原转化酶在卵巢细胞中暂时表达。随着从二级次级卵泡向窦前卵泡的转变，只有PCSK5 mRNA显着升高。激活素A选择性增强培养的双层次级卵泡中PCSK5 mRNA的表达并降低弗林蛋白酶和PCSK6的表达。 dec-RVKR-氯甲基酮 (CMK) 是一种高度特异性且有效的枯草杆菌蛋白酶样原转化酶竞争性抑制剂，对原转化酶活性的抑制可显着阻碍小鼠颗粒细胞中抑制素 α 和 β 亚基的成熟。 PC5/6 在弗林蛋白酶缺陷细胞中的过度表达导致抑制素 α 和 βB 亚基成熟增加。我们的数据支持前转化酶 PCSK5 在卵泡发生过程中卵巢抑制素亚基加工中的作用，并表明该酶可能是抑制素和激活素生物利用度的重要调节剂。
Inhibin and activin are essential dimeric glycoproteins belonging to the transforming growth factor-beta (TGFβ) superfamily. Inhibin is a heterodimer of α- and β-subunits, whereas activin is a homodimer of β-subunits. Production of inhibin is regulated during the reproductive cycle and requires the processing of pro-ligands to produce mature hormone. Furin is a subtilisin-like proprotein convertase (proconvertase) that activates precursor proteins by cleavage at basic sites during their transit through the secretory pathway and/or at the cell surface. We hypothesized that furin-like proconvertases are central regulators of inhibin α- and β-subunit processing within the ovary. We analyzed the expression of the proconvertases furin, PCSK5, PCSK6, and PCSK7 in the developing mouse ovary by real-time quantitative RT-PCR. The data showed that proconvertase enzymes are temporally expressed in ovarian cells. With the transition from two-layer secondary to pre-antral follicle, only PCSK5 mRNA was significantly elevated. Activin A selectively enhanced expression of PCSK5 mRNA and decreased expression of furin and PCSK6 in cultured two-layer secondary follicles. Inhibition of proconvertase enzyme activity by dec-RVKR-chloromethylketone (CMK), a highly specific and potent competitive inhibitor of subtilisin-like proconvertases, significantly impeded both inhibin α- and β-subunit maturation in murine granulosa cells. Overexpression of PC5/6 in furin-deficient cells led to increased inhibin α- and βB-subunit maturation. Our data support the role of proconvertase PCSK5 in the processing of ovarian inhibin subunits during folliculogenesis and suggest that this enzyme may be an important regulator of inhibin and activin bioavailability.
登录
查看更多内容
DOI：
10.1073/pnas.90.14.6691
发表时间：
1993-07-15
影响因子：
11.1
作者：
LUSSON, J;VIEAU, D;SEIDAH, NG
通讯作者：
SEIDAH, NG
影响因子：
--
作者：
Mason, AJ;Farnworth, PG;Sullivan, J
通讯作者：
Sullivan, J
影响因子：
4
作者：
Pangas, SA;Woodruff, TK
通讯作者：
Woodruff, TK
DOI：
10.1186/1477-7827-1-76
发表时间：
2003-11-03
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Thomas, Fiona H;Armstrong, David G;Telfer, Evelyn E
通讯作者：
Telfer, Evelyn E
影响因子：
4.8
作者：
Kipp, Jingjing L.;Kilen, Signe M.;Mayo, Kelly E.
通讯作者：
Mayo, Kelly E.