Department of Psychology and Committee on Neurobiology, Institute for Mind and Biology, University of Chicago, 940 East 57th Street, Chicago, Illinois 60637, USA.
Endocrinology. 2010 Feb;151(2):714-21. doi: 10.1210/en.2009-0710. Epub 2009 Dec 4.
Environmental day length drives nocturnal pineal melatonin secretion, which in turn generates or entrains seasonal cycles of physiology, reproduction, and behavior. In mammals, melatonin (MEL) binds to a number of receptor subtypes including high-affinity (MT1 and MT2) and low-affinity (MT3, nuclear orphan receptors) binding sites, which are distributed throughout the central nervous system and periphery. The MEL receptors that mediate photoperiodic reproductive and behavioral responses to MEL have not been identified in a reproductively photoperiodic species. Here I tested the hypothesis that MT1 receptors are necessary and sufficient to engage photoperiodic responses by challenging male Siberian hamsters (Phodopus sungorus), a species that does not express functional MT2 receptors, with ramelteon (RAM), a specific MT1/MT2 receptor agonist. In hamsters housed in a long-day photoperiod, late-afternoon RAM treatment inhibited gonadotropin secretion, induced gonadal regression, and suppressed food intake and body mass, mimicking effects of MEL. In addition, chronic (24 h/d) RAM infusions were sufficient to obscure endogenous MEL signaling, and these treatments attenuated gonadal regression in short days. Together, the outcomes indicate that signaling at the MT1 receptor is sufficient and necessary to mediate the effects of photoperiod-driven changes in MEL on behavior and reproductive function in a reproductively photoperiodic mammal.
环境日长驱动松果腺褪黑素的夜间分泌,进而产生或引发生理、生殖和行为的季节性周期。在哺乳动物中,褪黑素 (MEL) 与许多受体亚型结合,包括高亲和力 (MT1 和 MT2) 和低亲和力 (MT3、核孤儿受体) 结合位点,这些受体分布在中枢神经系统和外周。介导褪黑素对生殖和行为的光周期反应的 MEL 受体尚未在生殖光周期物种中确定。在这里,我通过用 ramelteon (RAM) 挑战雄性西伯利亚仓鼠 (Phodopus sungorus) 来测试 MT1 受体是参与光周期反应所必需和充分的假设,ramelteon 是一种特异性的 MT1/MT2 受体激动剂,这种物种不表达功能性 MT2 受体。在长日光照周期下饲养的仓鼠中,午后 RAM 处理抑制促性腺激素分泌,诱导性腺退化,并抑制食物摄入和体重,模拟 MEL 的作用。此外,慢性 (24 小时/天) RAM 输注足以掩盖内源性 MEL 信号,这些治疗方法减弱了短日照下的性腺退化。总之,这些结果表明,MT1 受体的信号传导足以介导光周期驱动的 MEL 变化对行为和生殖功能的影响,而无需生殖光周期哺乳动物中的 MT2 受体。