Epidermal growth factor (EGF) receptor ligands in the chicken ovary: I. Evidence for heparin-binding EGF-like growth factor (HB-EGF) as a potential oocyte-derived signal to control granulosa cell proliferation and HB-EGF and kit ligand expression.
Epidermal growth factor (EGF) receptor ligands in the chicken ovary: I. Evidence for heparin-binding EGF-like growth factor (HB-EGF) as a potential oocyte-derived signal to control granulosa cell proliferation and HB-EGF and kit ligand expression.
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DOI：
10.1210/en.2006-1383
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发表时间：
2007-07
期刊：
影响因子：
4.8
通讯作者：
Yajun Wang;Juan Li;Crystal Ying Wang;Amy Ho Yan Kwok;F. C. Leung
中科院分区：
文献类型：
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作者：
Yajun Wang;Juan Li;Crystal Ying Wang;Amy Ho Yan Kwok;F. C. Leung
越来越多的证据表明，表皮生长因子（EGF）受体（EGFR）配体和Kit配体（KL）在哺乳动物卵泡发育中起关键作用。由于对它们在非哺乳类脊椎动物卵巢中的表达知之甚少，我们的研究旨在研究HB-EGF和KL在鸡卵巢中的表达、激素调节和相互作用。半定量RT-PCR结果显示，随着卵巢发育，卵巢HB-EGF表达量显著增加。与这一发现一致，HB-EGF被证明主要由生长中的卵母细胞产生，并能够刺激前层（3 mm）和排卵前卵泡（F5和F1）中颗粒细胞的增殖。虽然HB-EGF的表达主要局限于卵母细胞，但它在培养的颗粒细胞中的表达可以被HB-EGF和其他EGFR配体（包括EGF和TGF-α）短暂而强烈地诱导。10 μ M AG 1478或100 μ M PD 98059可完全阻断HB-EGF的诱导作用，提示HB-EGF的作用是由EGFR和细胞内MAPK/ERK信号通路介导的。与哺乳动物不同，只有KL-1，而不是其他三种亚型（KL-2，-3和-4），被检测到主要在鸡卵巢中表达。有趣的是，KL在未分化和分化的颗粒细胞中的表达可以被HB-EGF瞬时下调，这意味着生长中的卵母细胞和周围的颗粒细胞之间的卵泡内通信通过EGFR配体和KL的相互作用。总的来说，我们的数据表明，HB-EGF可能是一个旁分泌信号从卵母细胞调节颗粒细胞增殖和HB-EGF和KL表达在卵巢卵泡发育。
There is increasing evidence that epidermal growth factor (EGF) receptor (EGFR) ligand and Kit ligand (KL) play critical roles in controlling follicular development in mammals. Because little is known about their expressions in the ovary of nonmammalian vertebrate, our study aimed to examine the expression, hormonal regulation, and interaction of HB-EGF and KL in the chicken ovary. Using semiquantitative RT-PCR, we demonstrated that ovarian HB-EGF expression increased dramatically with the posthatching ovarian growth. In line with this finding, HB-EGF was shown to be produced primarily by the growing oocytes and capable of stimulating the proliferation of granulosa cells in prehierarchal (3 mm) and preovulatory follicles (F5 and F1). Although HB-EGF expression is mainly restricted to the oocytes, its expression in cultured granulosa cells could be transiently yet strongly induced by HB-EGF and other EGFR ligands including EGF and TGF-alpha. And the inducing effect of HB-EGF was completely abolished by AG1478 (10 microM) or PD98059 (100 microM), indicating that the action of HB-EGF is mediated by EGFR and intracellular MAPK/ERK signaling pathway. Unlike mammals, only KL-1, not the other three isoforms identified (KL-2, -3, and -4), was detected to be predominantly expressed in the chicken ovary. Interestingly, KL expression in undifferentiated and differentiated granulosa cells could be transiently down-regulated by HB-EGF, implying an intrafollicular communication between growing oocyte and surrounding granulosa cells through the interplay of EGFR ligand and KL. Collectively, our data suggest that HB-EGF is likely a paracrine signal from the oocyte to regulate granulosa cell proliferation and HB-EGF and KL expression during ovarian follicular development.