Region‐Specific Expression and Hormonal Regulation of the First Exon Variants of Rat Prolactin Receptor mRNA in Rat Brain and Anterior Pituitary Gland

Abstract

Recent studies have revealed the occurrence of five first exon variants of the rat prolactin receptor mRNA, suggesting that multiple promoters direct prolactin receptor transcription in response to different regulatory factors. In the present study, regional expression of these first exon variants, as well as two prolactin receptor subtypes generated by alternative splicing, was examined in the brains and anterior pituitary glands of female rats. Expression of the long-form was detected in the choroid plexus, hypothalamus, hippocampus, cerebral cortex and anterior pituitary gland, whereas the short form was detected only in the choroid plexus. E1-3 mRNA, a first exon variant, was detected in the choroid plexus, hypothalamus, and anterior pituitary gland, whereas E1-4 was detected only in the choroid plexus. Other variants were not detectable by the polymerase chain reaction protocol employed in this study. Ovariectomy increased the short form in the choroid plexus and the E1-3 expression in the choroid plexus and pituitary gland, but changes in the long-form and E1-4 expression were minimal. Replacement of oestrogens and prolactin suggest that oestrogens down-regulate E1-3 expression in the choroid plexus and pituitary gland, and that the negative effect of oestrogen is mediated by prolactin in the pituitary gland. The present results revealed the region-specific promoter usage in prolactin receptor mRNA transcription, as well as the involvement of oestrogens in the regulation of E1-3 mRNA expression in the brain and pituitary gland.

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

“…However, the sequence of Prlr-S4 cDNA was completely identical with that of the corresponding regions of Prlr gene of the C57BL/6 strain, and no pseudogene sequence was found in this mouse strain. In the rat choroid plexus, the expression levels of both the mRNAs increase during lactation (Ouhtit et al 1993, Bakowska & Morrell 1997, Augustine et al 2003, Nogami et al 2007. In this study, the expression levels of the PRLR-L and PRLR-S4 variants were significantly increased in the lactating mice compared with those in the diestrus mice and were decreased in the PRL-deficient mice compared with the levels in the PRL-normal (i.e.…”

“…In addition, it has been reported that PRL enhances its own uptake in the choroid plexus (Mangurian et al 1992). Supporting this function, a high level of PRLR expression in the choroid plexus has been observed during lactation when the plasma PRL level is also high (Muccioli & Di Carlo 1994, Escalada et al 1996, Sugiyama et al 1996, Pi & Grattan 1999, Augustine et al 2003, Pi et al 2003, Nogami et al 2007, Anderson et al 2008. Also, PRLR expression in this brain region increases during the stress response, accompanying an increase in the plasma PRL level (Fujikawa et al 1995).…”

Regulation of Prolactin Receptor Gene Expression in the Rat Choroid Plexus via Transcriptional Activation of Multiple First Exons during Postnatal Development and Lactation

“…the E1 4 first exon is located in the downstream region of exon 2; therefore, E1 4 mrNa lacks the exon 2 sequence [34]. a recent study detected the expression of E1 3 -, E1 4 -, and E1 5 -PRLR mrNas, but not E1 1 -and E1 2 -PRLR mrNas, in the rat choroid plexus [27]. therefore, the current study used real-time PCR to evaluate the expression levels of the E1 3 -PRLR, E1 4 -PRLR, E1 5 -PRLR, and total PRLR mRNAs.…”

“…PrL is known to be transported from the blood to the cerebrospinal fluid (CSF) via a PrLr-mediated system in the choroid plexus [37], and PrL enhances its own uptake in the choroid plexus [21]. Many studies have reported an increase in PRLR mrNa levels in the choroid plexus during lactation that correlate with plasma PrL level increases [1,2,13,24,27,30,31,33]. These findings suggest that regulation of PRLR expression in the choroid plexus is critical for PrL action in the brain.…”

“…the E1 1 variant of PRLR mRNA is expressed specifically in gonadal tissues [17], whereas the E1 2 variant is transcribed in the liver and kidney [22,35]. the E1 3 variant is expressed generically in a wide range of tissues [18], whereas the E1 4 variant is expressed preferentially in the cerebrum, including the choroid plexus [27,34]. the E1 5 variant is transcribed in the brain, liver, and kidney [35].…”