Madan Pavneesh, Bridges Phillip J, Komar Carolyn M, Beristain Alexander G, Rajamahendran Rajadurai, Fortune Joanne E, MacCalman Colin D
Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada.
Biol Reprod. 2003 Nov;69(5):1506-14. doi: 10.1095/biolreprod.102.013714. Epub 2003 Jul 9.
Extensive remodeling of the extracellular matrix occurs in the ovary during the periovulatory period. Matrix metalloproteinases and their endogenous inhibitors, tissue inhibitors of metalloproteinases, are believed to play integral roles in this highly regulated series of cellular events, but their specific roles remain unclear. Recent cloning studies have identified a novel family of metalloproteinases, the ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) family. The regulated expression of distinct ADAMTS subtypes has been shown to be required for tissue morphogenesis during embryonic development and for maintaining the integrity of tissues in the adult. In the present studies, we have determined that multiple ADAMTS subtypes are present in the bovine ovary using a reverse transcription-polymerase chain reaction strategy. In particular, ADAMTS-1, -2, -3, -4, -5 (also known as ADAMTS-11), -7, -8, and -9, but not ADAMTS-6, -10, or -12, mRNA transcripts were detected in granulosa cells of nonatretic ovarian follicles and corpora lutea. The levels of mRNA for these ovarian ADAMTS were up- or down-regulated or remained unchanged in the granulosa and/or theca cells of the dominant follicle following the preovulatory surge of gonadotropins, depending on the subtype and/or the cell compartment, and in the corpus luteum during the luteal phase of the estrous cycle. The complex expression patterns observed for the distinct ADAMTS subtypes in the granulosa and theca cells of the periovulatory follicle and in the luteal tissues of the bovine ovary suggest that these novel proteases mediate, at least in part, the remodeling events underlying folliculogenesis and ovulation and the formation, maintenance, and regression of the corpus luteum.
在排卵期前后,卵巢中会发生细胞外基质的广泛重塑。基质金属蛋白酶及其内源性抑制剂——金属蛋白酶组织抑制剂,被认为在这一系列高度调控的细胞事件中发挥着不可或缺的作用,但其具体作用仍不清楚。最近的克隆研究鉴定出了一个新的金属蛋白酶家族,即含血小板反应蛋白基序的解聚素样金属蛋白酶(ADAMTS)家族。已表明,不同ADAMTS亚型的调控表达对于胚胎发育期间的组织形态发生以及维持成体组织的完整性是必需的。在本研究中,我们采用逆转录-聚合酶链反应策略确定了牛卵巢中存在多种ADAMTS亚型。具体而言,在非闭锁卵泡颗粒细胞和黄体中检测到了ADAMTS-1、-2、-3、-4、-5(也称为ADAMTS-11)、-7、-8和-9的mRNA转录本,但未检测到ADAMTS-6、-10或-12的mRNA转录本。促性腺激素排卵前激增后,这些卵巢ADAMTS的mRNA水平在优势卵泡的颗粒细胞和/或卵泡膜细胞中,根据亚型和/或细胞区室,以及在发情周期黄体期的黄体中,会上调、下调或保持不变。在排卵前卵泡的颗粒细胞和卵泡膜细胞以及牛卵巢黄体组织中观察到的不同ADAMTS亚型的复杂表达模式表明,这些新型蛋白酶至少部分介导了卵泡发生、排卵以及黄体形成、维持和退化的潜在重塑事件。