Isolation and Characterization of Mammalian Reproductive Pheromones

众所周知，动物个体之间通过嗅觉系统进行的化学交流在哺乳动物生殖行为的各个方面都起着至关重要的作用，如领地行为、交配行为和母性行为。因此，信息素分子的分离和表征非常重要，不仅因为所获得的信息可以很容易地应用于提高家畜的繁殖效率和解决繁殖问题，而且因为分离或合成的信息素可以作为神经科学研究领域中研究大脑功能之谜的有力工具。然而，与无脊椎动物不同，哺乳动物信息素的研究迄今尚未取得很大进展，这主要是由于缺乏合适的生物测定系统来评估哺乳动物等高等脊椎动物的信息素活性。在本研究中，我们利用下丘脑GnRH脉冲发生器活性的电生理表现作为参数，建立了一种新的哺乳动物生殖信息素的生物测定系统，该系统具有高特异性和重复性。通过这种独特的生物测定，我们已经能够证明雄性山羊毛或其乙醚提取物的气味在去卵巢山羊体内瞬间加速GnRH脉冲产生，用雌二醇处理并保持在长日光周期下。相比之下，去势山羊的毛发气味没有任何影响，表明信息素的产生和分泌依赖于雄激素。由于信息素物质的应用可以相对于GnRH脉冲精确地计时，而且效果可以在实时的基础上进行评估，这一过程将为我们提供分离哺乳动物信息素的机会。对物质(S)的进一步化学表征研究目前正在进行中。

It has been well-known that the chemical communication through the olfactory system between individual animals plays an essential role in various aspects of reproductive behavior in mammals, such as territorial behavior, mating behavior and maternal behavior. Isolation and characterization of pheromone molecules are, therefore, important not only because the obtained information can be readily applied to improving the reproductive efficiency and solving reproductive problems in domestic animals but also because the isolated or synthesized pheromones could be used as potent tools in the research field of neuroscience for studying the mystery of brain functions. Unlike in invertebrate species, however, the research on mammalian pheromones has not yet been advanced much so far mainly due to the lack of appropriate bioassay system to assess the pheromonal activity in higher vertebrates such as mammalian species.In the present study, we have established a novel bioassay system with high specificity and reproducibility for mammalian reproductive pheromones, known as the cause of "male effect" in domestic ruminant, using the electrophysiological manifestation of hypothalamic GnRH pulse generator activity as a parameter. By using this unique bioassay, we have been able to demonstrate that the odor of male goat hair or its ether extract accelerates GnRH pulse generator instantaneously in ovariectomized goats treated with estradiol and kept under longday photoperiod. In contrast, hair odor from castrated goats had no effect indicating the androgen dependent production and secretion of pheromones. Since the application of pheromone substance can be accurately timed in relation to the GnRH pulses and also the effect can be assessed on the real-time basis, this procedure will provide us with opportunity to isolate mammalian pheromones. Further study for the chemical characterization of substance (s) is now ongoing.