Department of Animal Science, Graduate School of Veterinary Medicine, Nippon Veterinary and Animal Science University, Musashino, Tokyo 180-8602, Japan.
J Mol Endocrinol. 2012 Feb 29;48(2):169-76. doi: 10.1530/JME-11-0122. Print 2012 Apr.
Prolactin (Prl) receptor (Prlr) gene is expressed in various brain regions, with the highest level present in the choroid plexus, a site for receptor-mediated PRL transport from the blood to cerebrospinal fluid. We investigated the regulatory mechanism of Prlr gene expression by PRL in the murine choroid plexus. We first examined the organization of the alternative first exons in murine Prlr gene. In addition to the three known first exons, mE1(1), mE1(2), and mE1(3), two first exons, mE1(4) and mE1(5), were newly identified by cDNA cloning. Each first exon variant of Prlr mRNA exhibited tissue-specific or generic expression. In the choroid plexus of mice, the expression levels of mE1(3)-, mE1(4)-, and mE1(5)-Prlr mRNAs were increased in the lactating mice compared with those in the diestrus mice. Furthermore, the expression level of mE1(4)-Prlr mRNA was decreased in the PRL-deficient (Prl(-/-)) mice compared with the PRL-normal (Prl(+/+) and Prl(+/-)) mice. In the ovariectomized Prl(-/-) mice, the expression level of mE1(4)-Prlr mRNA was significantly increased by PRL administration but not by 17β-estradiol administration. The expression levels of the two last exon variants of Prlr mRNAs, encoding the long and short cytoplasmic regions of PRLR, were also increased in the lactating mice and decreased in the Prl(-/-) mice. These findings suggest that PRL stimulates the Prlr gene expression through the transcriptional activation of mE1(4) first exon, leading to increases in the long- and short-form variants of Prlr mRNA in the murine choroid plexus.
催乳素 (Prl) 受体 (Prlr) 基因在各种脑区表达，其中脉络丛表达水平最高，是受体介导的催乳素从血液向脑脊液转运的部位。我们研究了催乳素在小鼠脉络丛中对 Prlr 基因表达的调控机制。我们首先检测了小鼠 Prlr 基因的替代第一外显子的组织。除了已知的三个第一外显子 mE1(1)、mE1(2)和 mE1(3)外，我们还通过 cDNA 克隆新鉴定了两个第一外显子 mE1(4)和 mE1(5)。Prlr mRNA 的每个第一外显子变体都表现出组织特异性或通用表达。在哺乳期小鼠的脉络丛中，与发情期小鼠相比，mE1(3)、mE1(4)和 mE1(5)-Prlr mRNA 的表达水平增加。此外，与 PRL 正常（Prl(+/+)和 Prl(+/-)）小鼠相比，PRL 缺乏（Prl(-/-)）小鼠的 mE1(4)-Prlr mRNA 表达水平降低。在去卵巢的 Prl(-/-)小鼠中，PRL 给药显著增加了 mE1(4)-Prlr mRNA 的表达水平，但 17β-雌二醇给药没有增加。Prlr mRNA 的两个最后外显子变体的表达水平，编码 PRLR 的长和短细胞质区域，在哺乳期小鼠中增加，在 Prl(-/-)小鼠中降低。这些发现表明，催乳素通过转录激活 mE1(4)第一外显子刺激 Prlr 基因表达，导致小鼠脉络丛中 Prlr mRNA 的长和短形式变体增加。
