Zhang Cheng, Xia Guoliang, Tsang Benjamin K
State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, Peoples' Republic of China.
Front Biosci (Elite Ed). 2011 Jun 1;3(4):1401-13. doi: 10.2741/E342.
Thyroid hormone (TH) is important for normal reproductive function. Our previous studies indicate that FSH increases preantral follicle growth in vitro, a response markedly enhanced by triiodothyronine (T3). However, the nature of this hormonal interaction is poorly understood. The objective of this study was to determine if and how T3 modulate FSH-induced expression and actions of granulosa cell intracellular survival and death intermediates. We investigated the possible involvement of Src and PI3K/Akt pathway in the regulation of granulosa cell survival. We demonstrated that, while ineffective alone (0.1-100 nM), T3 markedly enhanced FSH (100 ng/ml)-induced granulosa cell phospho-Src and phospho-Akt contents and Xiap expression in vitro. The effects of T3 were concentration-dependent, with maximal responses at 1.0 nM. FSH alone decreased Fas Ligand (FasL) content irrespective of the presence of T3. Co-treatment of cell with T3 and FSH decreased Fas content, although neither hormone alone elicited a significant response. Taken together, the present study demonstrates that T3 potentiates the cell survival action of FSH through Src- and PI3K-mediated Xiap up-regulation and decreased Fas and FasL expression.
甲状腺激素（TH）对正常生殖功能至关重要。我们之前的研究表明，促卵泡激素（FSH）可在体外促进窦前卵泡生长，而三碘甲状腺原氨酸（T3）可显著增强这一反应。然而，这种激素相互作用的本质尚不清楚。本研究的目的是确定T3是否以及如何调节FSH诱导的颗粒细胞内生存和死亡中间体的表达及作用。我们研究了Src和PI3K/Akt信号通路在调节颗粒细胞存活中的可能作用。我们发现，虽然T3单独作用无效（0.1 - 100 nM），但它能显著增强FSH（100 ng/ml）诱导的颗粒细胞磷酸化Src和磷酸化Akt含量以及X连锁凋亡抑制蛋白（Xiap）在体外的表达。T3的作用具有浓度依赖性，在1.0 nM时反应最大。单独使用FSH可降低Fas配体（FasL）含量，无论是否存在T3。T3与FSH共同处理细胞可降低Fas含量，尽管单独使用这两种激素均未引起显著反应。综上所述，本研究表明T3通过Src和PI3K介导的Xiap上调以及Fas和FasL表达降低来增强FSH的细胞存活作用。
