The liver X receptors and sterol regulatory element binding proteins alter progesterone secretion and are regulated by human chorionic gonadotropin in human luteinized granulosa cells.
The liver X receptors and sterol regulatory element binding proteins alter progesterone secretion and are regulated by human chorionic gonadotropin in human luteinized granulosa cells.
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DOI：
10.1016/j.mce.2018.01.011
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发表时间：
2018-09-15
影响因子：
4.1
通讯作者：
Bogan RL
中科院分区：
文献类型：
--
作者：
Xu Y;Hernández-Ledezma JJ;Hutchison SM;Bogan RL
在灵长类动物自发性黄体溶解过程中，肝脏X受体（LXR）靶基因表达增加，低密度脂蛋白受体（LDLR）表达减少。LXR是通过诱导其靶基因的转录来增加胆固醇流出的核受体。LDLR的转录受固醇调节元件结合蛋白（SREBP）调节。人绒毛膜促性腺激素（hCG）通过蛋白激酶A（PKA）防止黄体溶解并刺激孕酮合成。因此，我们的主要目标是：1）确定LXR激活和SREBP抑制对孕酮分泌和胆固醇代谢的影响，和2）确定hCG信号是否通过PKA调节人黄素化颗粒细胞中LXR和SREBP靶基因的转录。LXR激动剂T0901317和SREBP抑制剂法图他汀的联合作用显著降低了基础和hCG刺激的孕酮分泌，这与细胞内胆固醇储存减少有关。在T0901317存在下，hCG显著降低了LXR靶基因的表达，而hCG促进了有利于LDL摄取的转录变化。hCG的这些作用可被特异性PKA抑制剂逆转。第三个目标是解决一个两难的困境，关于LXR调节类固醇生成急性调节蛋白（星星）表达在灵长类动物和非灵长类动物类固醇生成细胞。T0901317诱导绵羊细胞中的星星表达和孕酮合成，但不诱导人类细胞，揭示了种属之间在LXR调节黄体功能方面的关键差异。总的来说，这些数据支持LXR诱导的胆固醇流出和通过SREBP抑制降低LDL摄取介导灵长类动物黄体溶解的假设，这是由hCG预防的。
There is increased expression of liver x receptor (LXR) target genes and reduced low density lipoprotein receptor (LDLR) during spontaneous luteolysis in primates. The LXRs are nuclear receptors that increase cholesterol efflux by inducing transcription of their target genes. Transcription of LDLR is regulated by sterol regulatory element binding proteins (SREBPs). Human chorionic gonadotropin (hCG) prevents luteolysis and stimulates progesterone synthesis via protein kinase A (PKA). Thus, our primary objectives are: 1) Determine the effects of LXR activation and SREBP inhibition on progesterone secretion and cholesterol metabolism, and 2) Determine whether hCG signaling via PKA regulates transcription of LXR and SREBP target genes in human luteinized granulosa cells. Basal and hCG-stimulated progesterone secretion was significantly decreased by the combined actions of the LXR agonist T0901317 and the SREBP inhibitor fatostatin, which was associated with reduced intracellular cholesterol storage. Expression of LXR target genes in the presence of T0901317 was significantly reduced by hCG, while hCG promoted transcriptional changes that favor LDL uptake. These effects of hCG were reversed by a specific PKA inhibitor. A third objective was to resolve a dilemma concerning LXR regulation of steroidogenic acute regulatory protein (STAR) expression in primate and non-primate steroidogenic cells. T0901317 induced STAR expression and progesterone synthesis in ovine, but not human cells, revealing a key difference between species in LXR regulation of luteal function. Collectively, these data support the hypothesis that LXR-induced cholesterol efflux and reduced LDL uptake via SREBP inhibition mediates luteolysis in primates, which is prevented by hCG.
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DOI：
10.1530/rep-09-0005
发表时间：
2010-01
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Bogan RL;Hennebold JD
通讯作者：
Hennebold JD
影响因子：
5.3
作者：
Laffitte, BA;Joseph, SB;Tontonoz, P
通讯作者：
Tontonoz, P
影响因子：
4.8
作者：
CAMERON, JL;STOUFFER, RL
通讯作者：
STOUFFER, RL
影响因子：
4.8
作者：
Puttabyatappa, Muraly;VandeVoort, Catharine A.;Chaffin, Charles L.
通讯作者：
Chaffin, Charles L.
影响因子：
3.6
作者：
Seto, Nickie L.;Bogan, Randy L.
通讯作者：
Bogan, Randy L.