Functional significance of the signal transduction pathways Akt and Erk in ovarian follicles: in vitro and in vivo studies in cattle and sheep.

Functional significance of the signal transduction pathways Akt and Erk in ovarian follicles: in vitro and in vivo studies in cattle and sheep.
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DOI:
10.1186/1757-2215-1-2
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发表时间:
2008-10-01
影响因子:
4
通讯作者:
Evans AC
Evans AC
中科院分区:
医学3区
文献类型:
--
作者:
Ryan KE;Glister C;Lonergan P;Martin F;Knight PG;Evans AC

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调节卵泡发育的细胞内信号传导机制尚不清楚;然而,我们最近发现显性卵泡与次级卵泡中Akt和Erk信号传导途径存在差异。本研究的目的是研究抑制Akt和Erk磷酸化对IGF和促性腺激素刺激的颗粒细胞和卵泡膜细胞功能的影响,以及对体内卵泡发育的影响。将牛颗粒细胞和卵泡膜细胞培养6天,并用FSH和/或IGF或LH与PD 98059(Erk抑制剂)和/或LY 294002(Akt抑制剂)组合刺激,并测定它们对细胞数量和激素分泌(雌二醇、激活素-A、卵泡抑素、孕酮和雄烯二酮)的影响。此外,在周期的第3天,用PD 98059和/或LY 294002在体内处理母羊的卵泡,并在48小时后回收卵泡。我们已经表明,促性腺激素和IGF刺激的颗粒细胞和卵泡膜细胞的激素分泌减少与PD 98059和LY 294002在体外治疗。此外,用PD 98059和LY 294002处理降低了体内卵泡生长和雌二醇产生。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。
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.
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