Collaborative Research: The Evolution of Endocrine Function; Discovering the Hormonal Control of Osmoregulation in Basal Vertebrates

所有生物都必须调节体内的盐和水含量才能正常运作和生存。在脊椎动物等更复杂的动物中，激素及其结合的受体是参与调节盐和水运输的关键信号分子。鱼类与水直接接触，它们必须主动从淡水中吸收盐分，并主动将其分泌到海水中，才能调节体内的盐浓度。迄今为止，关于激素控制盐调节的研究仅限于对高级鱼类的研究。本项目将研究两种基础脊椎动物，七鳃鳗和鲟鱼的盐调节激素控制。研究人员将研究由脑垂体分泌的两种激素——生长激素和催乳素及其受体是如何被外部盐度改变的。这项研究将确定这些激素对七鳃鳗和鲟鱼耐受外部盐度变化的能力的影响。这些研究结果将有助于了解这些激素的功能进化，进而可以应用于提高农业鱼类生产和入侵七鳃鳗的管理。研究结果将迅速转移到比较内分泌学和生理学的教科书中，发表在同行评议的期刊上，并在科学会议上分享。该奖项支持的研究将调查渗透调节激素在水生脊椎动物中的功能进化。我们目前对水生脊椎动物渗透调节的激素控制的了解几乎完全来自于高级硬骨鱼（硬骨鱼），并且没有关于垂体激素如何控制基础脊椎动物渗透调节的信息。现在已经确定，催乳素（PRL）对大多数硬骨鱼在淡水（FW）中的生存至关重要，而生长激素（GH），至少在某些谱系中，促进海水中的渗透调节（SW）。作为基础脊椎动物的七鳃鳗和作为基础硬骨鱼的软骨动物（包括鲟鱼）具有与硬骨鱼相同的渗透调节策略（即，无论外部盐度如何，都能保持几乎恒定的等离子体离子水平），但目前还没有关于PRL或GH在七鳃鳗或软骨动物的渗透调节中是否起作用的信息。有强有力的证据表明，七鳃鳗只拥有垂体激素（GH）的PRL/GH家族的一个成员，这使得它们对这些研究尤为重要。我们的具体目的是：1)确定生长激素和生长激素受体对盐度变化的响应；2)测定生长激素在七鳃鳗体内的渗透调节作用；3)确定GH和PRL在鲟鱼体内的渗透调节作用。对于每个物种，我们将研究FW和SW之间相互转移的生理和内分泌反应的时间过程。我们将利用重组技术制备七鳃鳗生长激素，以建立同源的放射免疫和放射受体检测方法，并确定其体内和体外的渗透调节作用。

All living organisms must regulate their internal salt and water content to function routinely and survive. In more complex animals, such as vertebrates, hormones and the receptors to which they bind are critical signaling molecules involved in regulation of salt and water transport. Fish are in direct contact with water, and they must actively take up salts from freshwater and actively secrete them in seawater to be able to regulate internal salt concentrations. To date research on the hormonal control of salt regulation has been limited to studies on advanced fish species. This project will examine the hormonal control of salt regulation in two basal vertebrates, lamprey eel and sturgeon. The researchers will examine how growth hormone and prolactin, two hormones secreted by the pituitary gland, and their receptors are altered by external salinity. This research will determine the effect of these hormones on the ability of lamprey and sturgeon to tolerate changes in external salinity. The results of these studies will yield insights about the functional evolution of these hormones, which in turn could be applied to enhancing agricultural production of fish and management of invasive lamprey. The results will be rapidly transferred to textbooks in comparative endocrinology and physiology, published in peer-reviewed journals, and shared at scientific meetings. Studies supported by this award will investigate the functional evolution of osmoregulatory hormones in aquatic vertebrates. Our current understanding of the hormonal control of osmoregulation in aquatic vertebrates comes almost entirely from advanced bony fish (teleosts), and there is no information on how pituitary hormones control osmoregulation in basal vertebrates. It is now well-established that prolactin (PRL) is critical for survival of most teleosts in freshwater (FW) and that growth hormone (GH), at least in some lineages, promotes osmoregulation in seawater (SW). Lamprey, as basal vertebrates, and chondrosteans (including sturgeon), as basal bony fish, have the same osmoregulatory strategy as teleosts (namely, maintaining nearly constant levels of plasma ions irrespective of external salinity), yet there is currently no information on whether PRL or GH play a role in osmoregulation of either lamprey or chondrosteans. There is strong evidence that lamprey possess only one member of the PRL/GH family of pituitary hormones (GH), making them especially critical for these studies. Our specific aims are: 1) to determine the response of GH and GH receptor to salinity change in lamprey; 2) to determine the osmoregulatory actions of GH in lamprey; and 3) to determine the osmoregulatory roles of GH and PRL in sturgeon. For each species we will examine the time course of physiological and endocrine responses to reciprocal transfers between FW and SW. We will utilize recombinant technology to make lamprey GH in order to develop homologous radioimmuno- and radioreceptor- assays, and determine its osmoregulatory actions in vivo and in vitro.