School of Agriculture Food Science and Veterinary Medicine, Conway Institute, College of Life Science, University College Dublin, Belfield, Dublin 4, Ireland.
J Ovarian Res. 2008 Oct 1;1(1):2. doi: 10.1186/1757-2215-1-2.
The intracellular signalling mechanisms that regulate ovarian follicle development are unclear; however, we have recently shown differences in the Akt and Erk signalling pathways in dominant compared to subordinate follicles. The aim of this study was to investigate the effects of inhibiting Akt and Erk phosphorylation on IGF- and gonadotropin- stimulated granulosa and theca cell function in vitro, and on follicle development in vivo.
Bovine granulosa and theca cells were cultured for six days and stimulated with FSH and/or IGF, or LH in combination with PD98059 (Erk inhibitor) and/or LY294002 (Akt inhibitor) and their effect on cell number and hormone secretion (estradiol, activin-A, inhibin-A, follistatin, progesterone and androstenedione) determined. In addition, ovarian follicles were treated in vivo with PD98059 and/or LY294002 in ewes on Day 3 of the cycle and follicles were recovered 48 hours later.
We have shown that gonadotropin- and IGF-stimulated hormone production by granulosa and theca cells is reduced by treatment with PD98059 and LY294002 in vitro. Furthermore, treatment with PD98059 and LY294002 reduced follicle growth and oestradiol production in vivo.
These results demonstrate an important functional role for the Akt and Erk signalling pathways in follicle function, growth and development.
调控卵巢卵泡发育的细胞内信号机制尚不清楚；然而，我们最近发现优势卵泡与从属卵泡在 Akt 和 Erk 信号通路方面存在差异。本研究旨在探讨抑制 Akt 和 Erk 磷酸化对 IGF 和促性腺激素刺激体外颗粒细胞和膜细胞功能的影响，以及对体内卵泡发育的影响。
牛颗粒细胞和膜细胞培养 6 天，用 FSH 和/或 IGF 或 LH 联合 PD98059（Erk 抑制剂）和/或 LY294002（Akt 抑制剂）刺激，并测定细胞数量和激素分泌（雌二醇、激活素-A、抑制素-A、卵泡抑素、孕酮和雄烯二酮）的变化。此外，在绵羊周期第 3 天用 PD98059 和/或 LY294002 对卵巢卵泡进行体内处理，48 小时后回收卵泡。
我们已经表明，在体外，促性腺激素和 IGF 刺激颗粒细胞和膜细胞的激素产生被 PD98059 和 LY294002 处理所减少。此外，PD98059 和 LY294002 的处理减少了体内卵泡生长和雌激素的产生。
这些结果表明 Akt 和 Erk 信号通路在卵泡功能、生长和发育中具有重要的功能作用。
