FOXL2 activates P450 aromatase gene transcription:: towards a better characterization of the early steps of mammalian ovarian development
FOXL2 activates P450 aromatase gene transcription:: towards a better characterization of the early steps of mammalian ovarian development
复制标题
DOI：
10.1677/jme.1.01947
复制
发表时间：
2006-06-01
影响因子：
3.5
通讯作者：
Pailhoux, Eric
中科院分区：
文献类型：
--
作者：
Pannetier, Maelle;Fabre, Stephane;Pailhoux, Eric
以前的研究已经证明FOXL2在不同脊椎动物的卵巢分化过程中起着至关重要的作用。在轮询的双性综合征(PIS)中，它的转录消失主要是导致山羊卵巢发育的第一步芳香酶(CYP19)表达的急剧下降。在本研究中，我们对山羊卵巢的早期发育提供了更好的描述，并提供了实验证据，证明FOXL2通过其卵巢特异性启动子2直接转录激活了CYP19基因。此外，FOXL2和CYP19蛋白在卵巢中的定位及其在雌性性腺中的表达情况强调了FOXL2辅助因子(S)参与调控CYP19转录。表达分析表明，激活素-βA可以被认为是这些FOXL2辅助因子之一的有力候选者。最后，我们讨论了激活素和雌激素在生殖细胞减数分裂前的体细胞和生发细胞增殖中的作用的证据。山羊的这段时间为20天，而小鼠的这段时间似乎没有。这种物种特异性的差异可以解释XX山羊PIS-/-和XX小鼠Fox12(-/-)之间的表型差异。
Previous studies have equated FOXL2 as a crucial actor in the ovarian differentiation process in different vertebrate species. Its transcriptional extinction in the polled intersex syndrome (PIS) leads primarily to a drastic decrease of aromatase (CYP19) expression in the first steps of goat ovarian development. In this study, we provide a better characterization of early ovarian development in goat, and we provide experimental evidence demonstrating that FOXL2 represents a direct transcriptional activator of the CYP19 gene through its ovarian-specific promoter 2. Moreover, the ovarian location of FOXL2 and CYP19 proteins, together with their expression profiles in the female gonads, stress the involvement of FOXL2 co-factor(s) for regulating CYP19 transcription. Expressional analyses show that activin-beta A can be considered as a strong candidate for being one of these FOXL2 co-factors. Finally, we discuss evidence for a role of activin and estrogens in somatic and germinal cell proliferation occurring before germ cell meiosis. This period, of 20 days in goat, seems to have no equivalent in mouse. This species-specific difference could explain the phenotype discrepancy observed between XX goat PIS-/- and XX mouse Fox12(-/-).