Expression and functional role of peroxisome proliferator-activated receptor-γ in ovarian folliculogenesis in the sheep
Expression and functional role of peroxisome proliferator-activated receptor-γ in ovarian folliculogenesis in the sheep
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DOI：
10.1095/biolreprod.103.017244
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发表时间：
2003-11-01
影响因子：
3.6
通讯作者：
Monget, P
中科院分区：
文献类型：
--
作者：
Froment, P;Fabre, S;Monget, P
过氧化物酶体增殖物激活受体（PPARγ）是一种由脂肪酸及其衍生物和抗糖尿病药物格列酮激活的核受体，在控制脂质和葡萄糖稳态中发挥作用。在目前的工作中，我们通过研究 PPARgamma 在绵羊下丘脑-垂体-卵巢轴中的表达和功能，检验了 PPARgamma 在生殖组织中发挥作用的假设。在整个绵羊垂体和卵巢中检测到 PPARgamma 1 和 PPARgamma 2 蛋白和 mRNA，但在下丘脑提取物中未检测到。卵巢切片原位杂交将 PPARgamma mRNA 定位于卵泡颗粒层。有趣的是，小窦（直径 1-3 mm）中的 PPARgamma 表达高于排卵前卵泡（直径 > 5 mm）（P < 0.001），并且与健康状态无关。为了评估卵巢 PPARgamma 的生物活性，用 PPARgamma 响应元件驱动的报告构建体转染绵羊颗粒细胞。添加 PPARγ 配体罗格列酮可刺激报告基因表达，表明内源性 PPARγ 在体外绵羊颗粒细胞中具有功能。此外，罗格列酮在体外抑制颗粒细胞增殖（P < 0.05）并增加孕酮分泌（P < 0.05）。这种刺激作用在小卵泡的颗粒细胞中比在大卵泡的颗粒细胞中更强。相反，罗格列酮对体外绵羊垂体细胞的 LH、FSH、催乳素和生长激素分泌没有影响。总体而言，这些数据表明 PPARgamma 配体可能通过对颗粒细胞的直接作用而不是通过调节垂体激素分泌来刺激体内卵泡分化。
Peroxisome proliferator-activated receptor (PPARgamma) is a nuclear receptor that is activated by fatty acids and derivatives and the antidiabetic glitazones, which plays a role in the control of lipid and glucose homeostasis. In the present work, we tested the hypothesis that PPARgamma plays a role in reproductive tissues by studying its expression and function in the hypothalamo-pituitary-ovary axis in the sheep. PPARgamma 1 and PPARgamma 2 proteins and mRNAs were detected in whole ovine pituitary and ovary but not in hypothalamic extracts. in situ hybridization on ovarian section localized PPARgamma mRNA in the granulosa layer of follicles. Interestingly, PPARgamma expression was higher in small antral (1-3 mm diameter) than in preovulatory follicles (>5 mm diameter) (P < 0.001) and was not correlated with healthy status. To assess the biological activity of ovarian PPARgamma, ovine granulosa cells were transfected with a reporter construct driven by PPARgamma-responsive elements. Addition of rosiglitazone, a PPARgamma ligand, stimulated reporter gene expression, showing that endogenous PPARgamma is functional in ovine granulosa cells in vitro. Moreover, rosiglitazone inhibited granulosa cell proliferation (P < 0.05) and increased the secretion of progesterone in vitro (P < 0.05). This stimulation effect was stronger in granulosa cells from small than from large follicles. In contrast, rosiglitazone had no effect on LH, FSH, prolactin and growth hormone secretion by ovine pituitary cells in vitro. Overall, these data suggest that PPARgamma ligands might stimulate follicular differentiation in vivo likely through a direct action on granulosa cells rather than by modulating pituitary hormone secretion.