Department of Basic Sciences and Aquatic Medicine, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway.
Department of Animal Sciences, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
J Pineal Res. 2019 Oct;67(3):e12590. doi: 10.1111/jpi.12590. Epub 2019 Jun 23.
The hormone melatonin connects environmental cues, such as photoperiod and temperature, with a number of physiological and behavioural processes, including seasonal reproduction, through binding to their cognate receptors. This study reports the structural, functional and physiological characterization of five high-affinity melatonin receptors (Mtnr1aaα, Mtnr1aaβ, Mtnr1ab, Mtnr1al, Mtnr1b) in Atlantic salmon. Phylogenetic analysis clustered salmon melatonin receptors into three monophyletic groups, Mtnr1A, Mtnr1Al and Mtnr1B, but no functional representative of the Mtnr1C group. Contrary to previous studies in vertebrates, pharmacological characterization of four receptors in COS-7, CHO and SH-SY5Y cell lines (Mtnr1Aaα, Mtnr1Aaβ, Mtnr1Ab, Mtnr1B) showed induction of intracellular cAMP levels following 2-iodomelatonin or melatonin exposure. No consistent response was measured after N-acetyl-serotonin or serotonin exposure. Melatonin receptor genes were expressed at all levels of the hypothalamo-pituitary-gonad axis, with three genes (mtnr1aaβ, mtnr1ab and mtnr1b) detected in the pituitary. Pituitary receptors displayed daily fluctuations in mRNA levels during spring, prior to the onset of gonadal maturation, but not in autumn, strongly implying a direct involvement of melatonin in seasonal processes regulated by the pituitary. To the best of our knowledge, this is the first report of cAMP induction mediated via melatonin receptors in a teleost species.
褪黑素激素将环境线索（如光周期和温度）与许多生理和行为过程（包括季节性繁殖）联系起来，其通过与同源受体结合来实现这一功能。本研究报告了 5 种高亲和力褪黑素受体（Mtnr1aaα、Mtnr1aaβ、Mtnr1ab、Mtnr1al、Mtnr1b）在大西洋鲑鱼中的结构、功能和生理学特征。系统发育分析将鲑鱼褪黑素受体聚类为三个单系群：Mtnr1A、Mtnr1Al 和 Mtnr1B，但没有 Mtnr1C 组的功能代表。与先前在脊椎动物中的研究相反，在 COS-7、CHO 和 SH-SY5Y 细胞系中对 4 种受体（Mtnr1Aaα、Mtnr1Aaβ、Mtnr1Ab、Mtnr1B）的药理学特征进行的研究表明，2-碘褪黑素或褪黑素暴露后会诱导细胞内 cAMP 水平升高。在暴露于 N-乙酰-血清素或血清素后，未测量到一致的反应。褪黑素受体基因在下丘脑-垂体-性腺轴的所有水平上表达，在垂体中检测到 3 个基因（mtnr1aaβ、mtnr1ab 和 mtnr1b）。在春季性腺成熟之前，垂体受体的 mRNA 水平会出现每日波动，但在秋季不会，这强烈表明褪黑素直接参与了由垂体调节的季节性过程。据我们所知，这是首次在硬骨鱼类中报告通过褪黑素受体介导 cAMP 诱导的情况。
