A unique urinary constituent, 6-hydroxy-6-methyl-3-heptanone, is a pheromone that accelerates puberty in female mice
A unique urinary constituent, 6-hydroxy-6-methyl-3-heptanone, is a pheromone that accelerates puberty in female mice
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DOI：
10.1016/s1074-5521(99)80049-0
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发表时间：
1999-06-01
影响因子：
--
通讯作者：
Carmack, M
中科院分区：
文献类型：
--
作者：
Novotny, MV;Jemiolo, B;Carmack, M
背景：自20世纪60年代以来，雌性小鼠嗅觉介导的青春期加速（通过子宫重量的增加来测量）一直被观察到，但没有在结构上识别出活跃的化学信号。关于这种雄性来源的信息素是否是一种挥发性物质，文献中存在许多争议。我们研究了导致子宫重量增加的尿液成分的化学性质。结果：活性信息素为5,5-二甲基-2-乙基四氢呋喃-2-醇和/或其开链互变异构体（6-羟基-6-甲基-3-庚酮）。从尿液色谱活性组分中分离出一系列环乙烯醚。因为这些化合物不会加速青春期，我们假设这些醚是一种乳酸（5,5 -二甲基-2-乙基四氢呋喃-2-醇）的降解产物。然后用硅基化剂直接在小鼠尿提取物中检测乳酸。合成的6-羟基-6-甲基-3-庚酮具有较强的生物活性，而其结构相近的类似物则没有。结论：雄性家鼠在其尿液中排泄大量具有独特乳/羟基酮结构的挥发性物质。这种物质能够与不易挥发的尿液成分结合，如蛋白质或多肽，并且在加速青春期的生物测定中很活跃。关于青春期加速信息素挥发性的争论现在可以通过考虑挥发性乳/羟酮和尿蛋白的复合物来解释。
Background: Olfactorily mediated puberty acceleration in female mice (measured by an increase in uterine weight) has been observed since the 1960s without the active chemosignal being structurally identified. There are many controversies in the literature as to whether this male-originated pheromone is a volatile substance. We investigated the chemical nature of the urinary fractions that are responsible for the characteristic uterine weight increases.Results: The active pheromone was identified as 5,5-dimethyl-2-ethyltetrahydrofuran-2-ol and/or its open-chain tautomer (6-hydroxy-6-methyl-3-heptanone). A series of cyclic vinyl ethers were isolated from chromatographically active fractions of the urine. Because these compounds did not accelerate puberty, we postulated that these ethers were degradation products of a lactol (5,5 -dimethyl-2-ethyltetrahydrofuran-2-ol). The lactol was then detected directly in the mouse urine extract using a silylation agent. Synthetic 6-hydroxy-6-methyl-3-heptanone had strong biological activity, whereas its close structural analogs did not.Conclusions: The male house mouse excretes into its urine a large quantity of a volatile substance that has a unique lactol/hydroxyketone structure. This substance is capable of binding to the less volatile urinary constituents, such as proteins or peptides, and is active in puberty-acceleration bioassays. The controversies regarding the volatility of the puberty-accelerating pheromones can now be explained by considering a complex of volatile lactol/hydroxyketone and urinary proteins.