Ecophysiological and Environmental Toxicological Research Group, HUN-REN Balaton Limnological Research Institute, Tihany, Hungary.
Bioorganic Research Institute, Suntory Foundation for Life Sciences, Kyoto, Japan.
Front Endocrinol (Lausanne). 2024 Aug 12;15:1458422. doi: 10.3389/fendo.2024.1458422. eCollection 2024.
Despite the lack of endogenous synthesis and relevant nuclear receptors, several papers have been published over the decades claiming that the physiology of mollusks is affected by natural and synthetic sex steroids. With scant evidence for the existence of functional steroid nuclear receptors in mollusks, some scientists have speculated that the effects of steroids might be mediated via membrane receptors (i.e. via non-genomic/non-classical actions) - a mechanism that has been well-characterized in vertebrates. However, no study has yet investigated the ligand-binding ability of such receptor candidates in mollusks. The aim of the present study was to further trace the evolution of the endocrine system by investigating the presence of functional membrane sex steroid receptors in a mollusk, the great pond snail (). We detected sequences homologous to the known vertebrate membrane sex steroid receptors in the transcriptome and genome data: G protein-coupled estrogen receptor-1 (GPER1); membrane progestin receptors (mPRs); G protein-coupled receptor family C group 6 member A (GPRC6A); and Zrt- and Irt-like protein 9 (ZIP9). Sequence analyses, including conserved domain analysis, phylogenetics, and transmembrane domain prediction, indicated that the mPR and ZIP9 candidates appeared to be homologs, while the GPER1 and GPRC6A candidates seemed to be non-orthologous receptors. All candidates transiently transfected into HEK293MSR cells were found to be localized at the plasma membrane, confirming that they function as membrane receptors. However, the signaling assays revealed that none of the candidates interacted with the main vertebrate steroid ligands. Our findings strongly suggest that functional membrane sex steroid receptors which would be homologous to the vertebrate ones are not present in . Although further experiments are required on other molluscan model species as well, we propose that both classical and non-classical sex steroid signaling for endocrine responses are specific to chordates, confirming that molluscan and vertebrate endocrine systems are fundamentally different.
尽管没有内源性合成和相关的核受体，但几十年来已经发表了几篇论文，声称贝类的生理学受到天然和合成性激素的影响。由于贝类中功能性甾体核受体的证据很少，一些科学家推测，甾体的作用可能通过膜受体介导（即通过非基因组/非经典作用）- 这种机制在脊椎动物中得到了很好的描述。然而，尚未有研究调查这些受体候选物在贝类中的配体结合能力。本研究的目的是通过研究一种贝类，大型池塘蜗牛（）中功能性膜性激素受体的存在，进一步追踪内分泌系统的进化。我们在转录组和基因组数据中检测到与已知的脊椎动物膜性激素受体同源的序列：G 蛋白偶联雌激素受体 1（GPER1）；膜孕激素受体（mPR）；G 蛋白偶联受体家族 C 组 6 成员 A（GPRC6A）；和 Zrt 和 Irt 样蛋白 9（ZIP9）。序列分析，包括保守结构域分析、系统发育和跨膜结构域预测，表明 mPR 和 ZIP9 候选物似乎是同源物，而 GPER1 和 GPRC6A 候选物似乎是非同源受体。所有候选物瞬时转染到 HEK293MSR 细胞中都被发现位于质膜上，证实它们作为膜受体发挥作用。然而，信号转导测定表明，没有一个候选物与主要的脊椎动物甾体配体相互作用。我们的研究结果强烈表明，在 中不存在与脊椎动物同源的功能性膜性激素受体。尽管还需要在其他贝类模式物种上进行进一步的实验，但我们提出，经典和非经典的甾体激素信号对于内分泌反应是脊索动物特有的，这证实了贝类和脊椎动物的内分泌系统在根本上是不同的。
