Department of Biological Sciences, Florida International University, 11200 SW 8th St., Miami, FL 33199, USA.
Insect Biochem Mol Biol. 2011 Sep;41(9):660-9. doi: 10.1016/j.ibmb.2011.04.008. Epub 2011 May 3.
Juvenile hormone (JH) is a key regulator of metamorphosis and ovarian development in mosquitoes. Adult female Aedes aegypti mosquitoes show developmental and dynamically regulated changes of JH synthesis. Newly emerged females have corpora allata (CA) with low biosynthetic activity, but they produce high amounts of JH a day later; blood feeding results in a striking decrease in JH synthesis, but the CA returns to a high level of JH synthesis three days later. To understand the molecular bases of these dynamic changes we combined transcriptional studies of 11 of the 13 enzymes of the JH pathway with a functional analysis of JH synthesis. We detected up to a 1000-fold difference in the levels of mRNA in the CA among the JH biosynthetic enzymes studied. There was a coordinated expression of the 11 JH biosynthetic enzymes in female pupae and adult mosquito. Increases or decreases in transcript levels for all the enzymes resulted in increases or decreases of JH synthesis; suggesting that transcript changes are at least partially responsible for the dynamic changes of JH biosynthesis observed. JH synthesis by the CA was progressively increased in vitro by addition of exogenous precursors such as geranyl-diphosphate, farnesyl-diphosphate, farnesol, farnesal and farnesoic acid. These results suggest that the supply of these precursors and not the activity of the last 6 pathway enzymes is rate limiting in these glands. Nutrient reserves play a key role in the regulation of JH synthesis. Nutritionally deficient females had reduced transcript levels for the genes encoding JH biosynthetic enzymes and reduced JH synthesis. Our studies suggest that JH synthesis is controlled by the rate of flux of isoprenoids, which is the outcome of a complex interplay of changes in precursor pools, enzyme levels and external regulators such as nutrients and brain factors. Enzyme levels might need to surpass a minimum threshold to achieve a net flux of precursors through the biosynthetic pathway. In glands with low synthetic activity, the flux of isoprenoids might be limited by the activity of enzymes with low levels of expression.
保幼激素（JH）是蚊子变态和卵巢发育的关键调节剂。成年雌性埃及伊蚊表现出JH 合成的发育和动态调节变化。新出现的雌性具有低生物合成活性的成虫腺（CA），但一天后它们会产生大量的 JH；血液摄取导致 JH 合成显著减少，但 CA 在三天后恢复到高水平的 JH 合成。为了了解这些动态变化的分子基础，我们将 13 种 JH 途径中的 11 种酶的转录研究与 JH 合成的功能分析结合起来。我们在研究的 JH 生物合成酶中检测到 CA 中 mRNA 水平的差异高达 1000 倍。在雌性蛹和成年蚊子中，11 种 JH 生物合成酶的表达是协调的。所有酶的转录水平的增加或减少都会导致 JH 合成的增加或减少；这表明转录变化至少部分负责观察到的 JH 生物合成的动态变化。CA 中的 JH 合成通过添加外源前体（如香叶基二磷酸、法呢基二磷酸、法呢醇、法呢醛和法呢酸）在体外逐渐增加。这些结果表明，在这些腺体中，这些前体的供应而不是最后 6 种途径酶的活性是限速的。营养储备在 JH 合成的调节中起着关键作用。营养不足的雌性具有较低的 JH 生物合成酶编码基因的转录水平和较低的 JH 合成。我们的研究表明，JH 合成受异戊二烯通量的速率控制，这是前体池、酶水平和外部调节剂（如营养物质和脑因子）变化的复杂相互作用的结果。酶水平可能需要超过最低阈值才能实现生物合成途径中前体的净通量。在合成活性低的腺体中，异戊二烯的通量可能受到表达水平低的酶的活性限制。
