Characterization of multiple first exons in murine prolactin receptor gene and the effect of prolactin on their expression in the choroid plexus

• Published in: Journal of molecular endocrinology Vol. 48; no. 2; pp. 169 - 176
• Main Authors: Tabata, Hidemi, Kobayashi, Momoko, Ikeda, Junko H, Nakao, Nobuhiro, Saito, Toru R, Tanaka, Minoru
• Format: Journal Article
• Language: English
• Published: England Society for Endocrinology 01.04.2012
• Subjects: 17 beta -Estradiol; Amino Acid Sequence; Animals; Base Sequence; Blood; Brain; Cerebrospinal fluid; Choroid plexus; Choroid Plexus - physiology; Cloning; Estradiol - pharmacology; Estrous Cycle - physiology; Exons; Female; Gene expression; Gene Expression - drug effects; Humans; Lactation - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Ovariectomy; Prolactin; Prolactin - genetics; Prolactin - metabolism; Prolactin - pharmacology; Prolactin receptors; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein transport; Receptors, Prolactin - genetics; Receptors, Prolactin - metabolism; Regular papers; Transcription activation
• ISSN: 0952-5041; 1479-6813
• DOI: 10.1530/JME-11-0122

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, mE11, mE12, and mE13, two first exons, mE14 and mE15, 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 mE13-, mE14-, and mE15-Prlr mRNAs were increased in the lactating mice compared with those in the diestrus mice. Furthermore, the expression level of mE14-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 mE14-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 mE14 first exon, leading to increases in the long- and short-form variants of Prlr mRNA in the murine choroid plexus.