PNAS:英国学者揭示褪黑素与日长关系
2017年3月7日，国际著名学术期刊《美国国家科学院院刊》杂志在线发表了英国布里斯托大学Domingo Tortonese研究员的一篇研究论文研究揭示了生育时间对动物种群的延续至关重要，研究确定了动物是如何测量时间，控制季节性生育活动的。文章证明了“褪黑素对日长判断的季节性生理影响机制“。
在鸟类和哺乳动物中，生育适应的过程是由脑下垂体激素的释放来调节的，这些激素控制着多种功能，如繁殖、应激反应、以及动物生长新的外壳。然而，计算白天的长度，来判断是处于一年中的哪个季节是由褪黑激素来调节的。我们仅知道褪黑素是松果体在夜间释放的。直到现在，褪黑素是如何传达信号给垂体的，仍然是30年来的未解之谜。
以绵阳为实验模型，他们发现夜间褪黑素分泌的持续时间控制了靠近大脑的特定脑垂体区域中，不同形式的血管内皮生长因子(VEGF)的产生。VEGF能够防止冬季的血管生长，反而刺激夏天血管增长。
文章的共同一作Domingo Tortonese博士说，我们发现，这种褪黑素依赖的VEGF之间会形成两种互补效应。首先，它导致链接脑域脑下垂体的血管重塑;其次，它作为信号信使，作用于腺体不同区域的垂体细胞，产生激素来控制季节性的生育能力。
该研究阐述了，动物能够适应变化环境，调整繁殖时间的生理机制。这些发现将对农业产业，以及人类医学产生积极影响。
原文链接：
Mechanisms regulating angioGENEsis underlie seasonal control of pituitary function
原文摘要:
Seasonal changes in mammalian physiology, such as those affecting reproduction, hibernation, and metabolism, are controlled by pituitary hormones released in response to annual environmental changes. In temperate zones, the primary environmental cue driving seasonal reproductive cycles is the change in day length (i.e., photoperiod), encoded by the pattern of melatonin secretion from the pineal gland. However, although reproduction relies on hypothalamic gonadotrophin-releasing hormone output, and most cells producing reproductive hormones are in the pars distalis (PD) of the pituitary, melatonin receptors are localized in the pars tuberalis (PT), a physically and functionally separate part of the gland. How melatonin in the PT controls the PD is not understood. Here we show that melatonin time-dependently acts on its receptors in the PT to alter splicing of vascular endothelial growth factor (VEGF). Outside the breeding season (BS), angiogenic VEGF-A stimulates vessel growth in the infundibulum, aiding vascular communication among the PT, PD, and brain. This also acts on VEGF receptor 2 (VEGFR2) expressed in PD prolactin-producing cells known to impair gonadotrophin secretion. In contrast, in the BS, melatonin releases antiangiogenic VEGF-Axxxb from the PT, inhibiting infundibular angiogenesis and diminishing lactotroph (LT) VEGFR2 expression, lifting reproductive axis repression in response to shorter day lengths. The time-dependent, melatonin-induced differential expression of VEGF-A isoforms culminates in alterations in gonadotroph function opposite to those of LTs, with up-regulation and down-regulation of gonadotrophin gene expression during the breeding and nonbreeding seasons, respectively. These results provide a mechanism by which melatonin can control pituitary function in a seasonal manner.
作者：Domingo Tortonese
