Differential effects of sex steroid hormones on the expression of multiple first exons including a novel first exon of prolactin receptor gene in the rat liver

Abstract

In addition to the known four alternative first exons E1 1 , E1 2 , E1 3 and E1 4 of the rat prolactin receptor (PRL-R) gene, a novel first exon, E1 5 , was identified by cDNA cloning of the 58-end region of PRL-R mRNA in the rat liver. Genomic fragments containing E1 5 and its 58-or 38-flanking regions were also cloned from rat kidney genomic DNA. A sequence search for E1 5 revealed that E1 5 is located 49 kb upstream of exon 2 of the PRL-R gene in rat chromosome 2q16. RT-PCR analysis revealed that E1 5 was preferentially expressed in the liver, brain and kidney. Expression profiles of E1 2 -, E1 3 -and E1 5 -PRL-R mRNAs in the liver of male and female rats at 5 days of age and those at 8 weeks of age were examined by RT-PCR. The levels of E1 2 -PRL-R mRNA in the female rat increased remarkably in rats at 8 weeks of age compared with those at 5 days of age, and the levels of E1 5 -PRL-R mRNA in the male rat decreased markedly at 8 weeks of age compared with those at 5 days of age. In the female rat, the levels of E1 2 -PRL-R mRNA at 8 weeks of age decreased with ovariectomy performed at 4 weeks of age and recovered with the administration of -oestradiol. On the contrary, the levels of E1 5 -PRL-R mRNA increased with ovariectomy and decreased with the oestrogen treatment. In the male rat liver, the levels of E1 2 -PRL-R mRNA at 8 weeks of age increased strikingly with castration performed at 4 weeks of age and became undetectable with the administration of testosterone. The levels of E1 5 -PRL-R mRNA increased slightly with castration and were restored by testosterone treatment. Removal of gonadal tissues and sex steroid hormone treatment had no effect on the expression levels of E1 3 -PRL-R mRNA in both female and male rat livers. These results indicated that the expression of the PRL-R gene in the liver is regulated by the differential effects of sex steroid hormones on the transcription of the multiple first exons including the novel one.

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 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]. Previously, we showed that PrLr gene expression in the rat cerebrum increased during lactation in female rats while the postnatal development of male and female rats depended on the transcriptional activation of E1 4 [20,34].…”

“…in mammals, PRLR gene expression is regulated via the transcriptional activation of multiple alternative first exons that encode 5'-untranslated regions. Five first exons have been identified in the rat PRLR gene, i.e., E1 1 , E1 2 , E1 3 , E1 4 , and E1 5 [16,22,34,35]. 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].…”

“…Five first exons have been identified in the rat PRLR gene, i.e., E1 1 , E1 2 , E1 3 , E1 4 , and E1 5 [16,22,34,35]. 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].…”

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

“…In rat Prlr gene, five alternative first exons, E1 1 , E1 2 , E1 3 , E1 4 , and E1 5 , have been identified previously (Hu et al 1996, Moldrup et al 1996, Tanaka et al 2002. In rats, the E1 1 variant of Prlr mRNA is specifically expressed in the gonadal tissues (Hu et al 1997) and the E1 2 variant is transcribed in the liver and kidney (Moldrup et al 1996, Tanaka et al 2005. In addition, the E1 3 variant is expressed in a wide range of tissues (Hu et al 1998), whereas the E1 4 variant is preferentially expressed in the brain (Tanaka et al 2002).…”

“…In addition, the E1 3 variant is expressed in a wide range of tissues (Hu et al 1998), whereas the E1 4 variant is preferentially expressed in the brain (Tanaka et al 2002). Finally, the E1 5 variant is used in the brain, liver, and kidney (Tanaka et al 2005). In murine Prlr gene, three first exons homologous to rat E1 1 , E1 2 , and E1 3 (referred to as mE1 1 , mE1 2 , and mE1 3 respectively) have been detected to date (Davis & Linzer 1989, Hu et al 1997.…”