The regulated expression of the pregnancy-associated plasma protein-A in the rodent ovary: a proposed role in the development of dominant follicles and of corpora lutea.
The regulated expression of the pregnancy-associated plasma protein-A in the rodent ovary: a proposed role in the development of dominant follicles and of corpora lutea.
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DOI：
10.1210/endo.143.5.8769
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发表时间：
2002-05
期刊：
影响因子：
4.8
通讯作者：
A. Hourvitz;A. Kuwahara;J. Hennebold;Adriano B. Tavares;H. Negishi;T. Lee;G. Erickson;E. Adashi
中科院分区：
文献类型：
--
作者：
A. Hourvitz;A. Kuwahara;J. Hennebold;Adriano B. Tavares;H. Negishi;T. Lee;G. Erickson;E. Adashi
令人信服的证据表明，卵泡内的IGF-I系统构成了小鼠卵巢中FSH作用的强制性中介。在这个系统中，卵巢IGF结合蛋白-4导向的蛋白酶(IGFBP-4ase)可能起着关键作用。人类IGFBP-4酶已被证明与先前很好地描述的妊娠相关血浆蛋白-A(PAPP-A)相同。本文报道了小鼠PAPP-A基因的克隆、测序及其在小鼠卵巢中的表达和细胞定位。未处理的25天龄小鼠卵巢中未检测到PAPP-A基因的表达。经PMSG处理后，PAPP-A在明确的颗粒细胞和卵泡亚群中的表达随时间显著增加。具体地说，PMSG后3-36小时内，PAPP-A仅在有腔卵泡的颗粒膜细胞中可检测到。PMSG后48小时，PAPP-A在优势排卵前卵泡中的表达降至检测不到的水平。用人CG处理PMSG诱导的小鼠在优势卵泡的颗粒细胞中迅速重新诱导PAPP-A的表达，并在整个排卵和黄体化过程中保持在相对较高的水平。这些结果表明，促性腺激素刺激的PAPP-A基因表达在哺乳动物卵巢优势卵泡发育、排卵和黄体发生的生理过程中发挥了作用。颗粒细胞中促性腺激素依赖的PAPP-A的早期表达和持续时间的延长可能有助于降低抗促性腺激素IGFBP-4的表达。因此，成功的有腔卵泡发育、排卵和黄体形成可能取决于IGFBP-4-耗尽/PAPP-A-充足的环境，从而导致IGF-I充足的卵泡内微环境。
Compelling evidence exists displaying that the intrafollicular IGF-I system constitutes an obligatory mediator of FSH action in the murine ovary. Within this system, the ovarian IGF binding protein-4-directed protease (IGFBP-4ase) may have a critical role. Human IGFBP-4ase has been proved identical to the previously well-characterized pregnancy-associated plasma protein-A (PAPP-A). This communication reports the cloning and sequencing of the mouse PAPP-A cDNA as well as its expression and cellular localization in the mouse ovary. PAPP-A mRNA was undetectable in ovaries of untreated immature 25-d-old mice. Treatment with PMSG led to a marked time-dependent increase in PAPP-A expression in well-defined subsets of granulosa cells and follicles. Specifically, PAPP-A expression was detectable exclusively in centrifugally residing membrana granulosa cells of antral follicles during a 3- to 36-h period post PMSG. PAPP-A expression then fell to nondetectable levels in dominant preovulatory follicles at 48 h post PMSG. Treatment of PMSG-primed mice with human CG caused a rapid reinduction of PAPP-A expression in granulosa cells of dominant follicles and was sustained at relatively high levels throughout the ovulation and luteinization. These results suggest a role for gonadotropin-stimulated PAPP-A gene expression in the physiologic processes of dominant follicle development, ovulation, and luteogenesis in the mammalian ovary. The early onset and extended duration of gonadotropin-dependent PAPP-A expression in granulosa cells may serve to degrade the antigonadotropin IGFBP-4. Accordingly, successful antral follicle development, ovulation, and corpus luteum formation may be contingent on an IGFBP-4-deplete/PAPP-A-replete circumstance, hence resulting in an IGF-I-replete intrafollicular microenvironment.