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

Abstract

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 tissuespecific 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 K/K ) mice compared with the PRL-normal (Prl C/C and Prl C/K ) mice. In the ovariectomized Prl K/K mice, the expression level of mE1 4 -Prlr mRNA was significantly increased by PRL administration but not by 17b-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 K/K 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.

Zinc Finger Homeodomain Factor Zfhx3 Is Essential for Mammary Lactogenic Differentiation by Maintaining Prolactin Signaling Activity

“…In mice, five alternative first exons have been identified for Prlr, including E1 1 , E1 2 , E1 3 , E1 4 , and E1 5 ( Fig. 5H) (55). Little is known about how the putative promoters upstream of these first exons drive Prlr transcription and what factors bind to the promoter sequences.…”

Reproductive status affects the expression of prolactin receptor mRNA in the brain of female Damaraland mole-rats

“…Previous studies, administering radio-labelled prolactin to rats and mice have shown that high prolactin levels in the peripheral circulation result in increased prolactin uptake at the ChP, measured as the amount of radio-labelled prolactin found in the cerebrospinal fluid (Walsh et al 1978;Mangurian et al 1992;Brown et al 2016). Moreover, during lactation, a physiological condition of chronically high plasma prolactin levels, Prlr mRNA and protein expression at the ChP are significantly increased (Pi and Grattan 1999a;Pi and Grattan 1999b;Augustine et al 2003;Tabata et al 2012). Also, Prlr protein expression in the rostral and caudal ARC is increased during lactation (Pi and Grattan 1999b).…”

Prolactin transport into mouse brain is independent of prolactin receptor

“…Accompanying this physiologic state of hyperprolactinemia are a number of important adaptations that occur in the brain that prolactin is involved in mediating, such as the stimulation of maternal behavior, suppression of the stress response, and an increase in food intake (4). We have previously shown that there is a 3-to 5-fold increase in expression of prolactin receptors in the choroid plexus during lactation in the rat (12), and all prolactin receptor isoforms have been shown to have up-regulated expression in the mouse choroid plexus during lactation (24). In the mouse, we have shown a large increase in pSTAT5 expression in a number of brain regions during lactation (25), demonstrating an increase in responsiveness in the brain to prolactin during lactation.…”