Pan Bochen, Sengoku Kazuo, Takuma Naoyuki, Goishi Katsutoshi, Horikawa Michiharu, Tamate Kenichi, Ishikawa Mutsuo
Department of Obstetrics and Gynecology, Asahikawa Medical College, Midorigaokahigashi 2-1, Asahikawa 078-8510, Japan.
Mol Cell Endocrinol. 2004 Feb 12;214(1-2):1-8. doi: 10.1016/j.mce.2003.12.003.
We investigated the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and its receptors in the rat ovary to define the role of HB-EGF in the ovarian function. The expression pattern of HB-EGF mRNA and protein were studied by semi-quantitative RT-PCR and immuno-histochemistry using an antibody that was specifically stained for the precursor form of HB-EGF in naturally cycling rats and immature pseudo-pregnant rat models. The immuno-histochemical study showed that in naturally cycling rats, HB-EGF was expressed in most granulosa cells of early follicles and all the developing follicles but not in preovulatory follicles. This was supported by the semi-quantitative RT-PCR results in that the lowest level of HB-EGF mRNA during the estrous cycle was found in the evening of proestrous when the HB-EGF negative preovulatory follicles were most prominent. The results suggest that HB-EGF might be a mitogen for granulosa cells and down regulation of its expression may be necessary for the final maturation of follicles. In corpora lutea, luteal cells of older generation stained stronger than those of younger generation. Moreover, luteal cells of late luteal phase stained stronger than those of the mid and early luteal phases in the immature pseudo-pregnant rat models, indicating that the precursor form may be associated with death of luteal cells. Finally, of the two cognate receptors for HB-EGF, erbB1 was expressed in the rat ovary, but erbB4 was specifically not expressed in this organ. The spatial and temporal pattern of HB-EGF expression suggest that HB-EGF may an important local regulator of ovarian function and structure.
我们研究了肝素结合表皮生长因子样生长因子（HB-EGF）及其受体在大鼠卵巢中的表达，以确定HB-EGF在卵巢功能中的作用。使用特异性针对天然周期大鼠和未成熟假孕大鼠模型中HB-EGF前体形式染色的抗体，通过半定量RT-PCR和免疫组织化学研究了HB-EGF mRNA和蛋白的表达模式。免疫组织化学研究表明，在天然周期大鼠中，HB-EGF在早期卵泡的大多数颗粒细胞和所有发育中的卵泡中表达，但在排卵前卵泡中不表达。半定量RT-PCR结果支持了这一点，即在动情周期中，当HB-EGF阴性的排卵前卵泡最为突出时，在动情前期晚上发现HB-EGF mRNA水平最低。结果表明，HB-EGF可能是颗粒细胞的促有丝分裂原，其表达的下调可能是卵泡最终成熟所必需的。在黄体中，老一代黄体细胞的染色比年轻一代更强。此外，在未成熟假孕大鼠模型中，黄体后期的黄体细胞染色比黄体中期和早期更强，表明前体形式可能与黄体细胞的死亡有关。最后，在HB-EGF的两种同源受体中，erbB1在大鼠卵巢中表达，但erbB4在该器官中特异性不表达。HB-EGF表达的时空模式表明，HB-EGF可能是卵巢功能和结构的重要局部调节因子。
