Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control
Identification of Melatonin-Regulated Genes in the Ovine Pituitary Pars Tuberalis, a Target Site for Seasonal Hormone Control
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DOI：
10.1210/en.2008-0834
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发表时间：
2008-11-01
期刊：
影响因子：
4.8
通讯作者：
Loudon, Andrew S. I.
中科院分区：
文献类型：
--
作者：
Dupre, Sandrine M.;Burt, Dave W.;Loudon, Andrew S. I.
垂体的结节部（PT）表达高密度的褪黑激素（MEL）受体，并且被认为通过解码夜间褪黑激素分泌的变化来调节季节性生理。已知生物钟基因在PT中表达，以响应MEL分泌的下降（Per 1）和开始（Cry 1），但迄今为止，对该关键MEL靶位点的其他分子变化知之甚少。为了确定可能参与昼夜和光周期转导机制的转录途径，我们进行了全基因组转录组分析，使用PT RNA从绵羊中分离，在24小时周期的三个时间点，无论是长或短的光周期。我们的研究结果揭示了153个转录本的表达在光周期之间的光-暗过渡和54个转录本的表达水平更全球性地改变了光周期（所有时间点合并）。夜间Cry 1诱导与NeuroD 1（神经源性分化因子1）、Pbef/Nampt（烟酰胺磷酸核糖转移酶）、Hif 1 α（缺氧诱导因子-1 α）和Kcnq 5（K+通道）编码基因的上调以及Ror β（一种关键时钟基因调节因子）的下调相关。使用原位杂交，我们证实了PT中Pbef/Nampt、NeuroD 1和Ror β表达的昼夜差异。用MEL处理绵羊增加了Cry 1、Pbef/Nampt、NeuroD 1和Hif 1 α的PT表达，但不增加Kcnq 5的表达。因此，我们的数据揭示了一个集群的Cry 1相关基因，是急性反应MEL和新的转录途径参与MEL行动的PT。（内分泌学149：5527-5539，2008）
The pars tuberalis (PT) of the pituitary gland expresses a high density of melatonin (MEL) receptors and is believed to regulate seasonal physiology by decoding changes in nocturnal melatonin secretion. Circadian clock genes are known to be expressed in the PT in response to the decline (Per1) and onset (Cry1) of MEL secretion, but to date little is known of other molecular changes in this key MEL target site. To identify transcriptional pathways that may be involved in the diurnal and photoperiod-transduction mechanism, we performed a whole genome transcriptome analysis using PT RNA isolated from sheep culled at three time points over the 24-h cycle under either long or short photoperiods. Our results reveal 153 transcripts where expression differs between photoperiods at the light-dark transition and 54 transcripts where expression level was more globally altered by photoperiod (all time points combined). Cry1 induction at night was associated with up-regulation of genes coding for NeuroD1 (neurogenic differentiation factor 1), Pbef/Nampt( nicotinamide phosphoribosyltransferase), Hif1 alpha (hypoxia-inducible factor-1 alpha), and Kcnq5 (K+ channel) and down-regulation of Ror beta, a key clock gene regulator. Using in situ hybridization, we confirmed day-night differences in expression for Pbef/Nampt, NeuroD1, and Ror beta in the PT. Treatment of sheep with MEL increased PT expression for Cry1, Pbef/Nampt, NeuroD1, and Hif1 alpha, but not Kcnq5. Our data thus reveal a cluster of Cry1-associated genes that are acutely responsive to MEL and novel transcriptional pathways involved in MEL action in the PT. (Endocrinology 149: 5527-5539, 2008)