EFFECTS OF 9-ENE-TETRAHYDROCANNABINOL ON EXPRESSION OF BETA-TYPE TRANSFORMING GROWTH-FACTORS, INSULIN-LIKE GROWTH FACTOR-I AND C-MYC GENES IN THE MOUSE UTERUS
EFFECTS OF 9-ENE-TETRAHYDROCANNABINOL ON EXPRESSION OF BETA-TYPE TRANSFORMING GROWTH-FACTORS, INSULIN-LIKE GROWTH FACTOR-I AND C-MYC GENES IN THE MOUSE UTERUS
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DOI：
10.1016/0960-0760(93)90160-x
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发表时间：
1993-06-01
影响因子：
4.1
通讯作者：
DEY, SK
中科院分区：
文献类型：
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作者：
DAS, SK;PARIA, BC;DEY, SK
采用Northern印迹杂交法检测大麻素对去卵巢成年小鼠子宫中转化生长因子β1、β2和β3、胰岛素样生长因子I和c-myc基因表达的影响。将小鼠暴露于9-烯-四氢大麻酚(THC)或联合注射雌二醇-17β(E_2)和/或孕酮(P_4)，然后在不同时间对子宫进行分析。在去卵巢大鼠子宫中持续存在着转化生长因子-β异构体信使核糖核酸(MRNAs)，THC处理后其水平无明显变化，而注射E224 h后，其表达水平略有升高。THC处理可通过将表达高峰的时间延长至12h，从而增强了E2mRNA的刺激效应。与之相比，E2THC处理后6h，THC显著提高了THC-β2mRNA的表达水平，并在不影响反应时间的情况下增强了这种反应。施加P4处理不能对抗这些反应中的任何一种。P4单独处理或与THC一起处理对这些转化生长因子-β亚型的mRNA水平没有显著影响。去卵巢小鼠子宫中IGF-I和c-myc的mRNAs水平较低，THC不改变这些mRNAs的水平。相反，E2处理引起IGF-I和c-myc mRNAs的快速但短暂的增加，THC拮抗c-myc mRNAs的快速反应，并改变IGF-ImR NA反应的时间。单独P4处理也引起这些mRNAs的短暂诱导，但THC不能拮抗这些作用。与单独注射E2或P4相比，注射P4+E2导致IGF-I和c-myc mRNA水平进一步温和上升。然而，THC并不能拮抗联合使用卵巢类固醇的这些短暂刺激作用。这些数据表明，THC不应被归类为雌激素样或抗雌激素样。然而，这种化合物可以调节(增强、拮抗和/或改变)卵巢类固醇对子宫基因表达的影响。
Effects of cannabinoid on expression of beta-type transforming growth factors (TGF-beta1,-beta2 and -beta3), insulin-like growth factor-I (IGF-I) and c-myc genes in the uteri of adult ovariectomized mice were examined using Northern blot hybridization. Mice were exposed to 9-ene-tetrahydrocannabinol (THC) alone or in combination with an injection of estradiol-17beta (E2) and/or progesterone (P4), and uteri were analyzed at various times thereafter. TGF-beta isoform messenger RNAs (mRNAs) persisted in ovariectomized uteri and their levels were not altered after THC treatment, whereas an injection of E2 caused a modest increase in TGF-beta1 and -beta3 mRNA levels at 24 h. Imposition of THC treatment advanced the stimulatory effects of E2 by changing the timing for the peak of TGF-beta3 mRNA levels to 12 h. In comparison, E2 treatment substantially elevated the levels of TGF-beta2 mRNA at 6 h, and THC potentiated this E2 response without affecting the timing for the response. Imposition of P4 treatment did not antagonize any of these responses. P4 treatment alone or with THC had insignificant effects on mRNA levels for these TGF-beta isoforms. Uterine levels of IGF-I and c-myc mRNAs were low in ovariectomized mice and THC did not alter these mRNA levels. In contrast, E2 treatment induced a rapid, but transient, increase in IGF-I and c-myc mRNAs, and THC antagonized the rapid c-myc mRNA response and altered the timing of the IGF-I mRNA response. P4 treatment alone also caused the transient induction of these mRNAs, but THC failed to antagonize these effects. An injection of P4 plus E2 resulted in further modest increases in IGF-I and c-myc mRNA levels as compared to E2 Or P4 treatment alone. However, THC did not antagonize these transient stimulatory effects of the combined ovarian steroids. The data suggest that THC should not be classified as estrogenic or antiestrogenic. However, this compound can modulate (potentiate, antagonize and/or alter timing) the effects of ovarian steroids on uterine gene expression.