Differential regulation of prolactin receptor mRNA expression in rat liver and kidney by testosterone and oestradiol

Abstract

Prolactin (PRL) exerts a wide variety of physiological effects on mammalian tissues through its receptor (PRL-R) on the target cells. PRL-R in rat tissue consists of two isoforms, the long and the short form, and the regulatory mechanisms of their mRNA expression in tissues are complex and diverse. The present study reports the differential regulation of PRL-R mRNA expression in rat liver and kidney by testosterone and oestradiol. Using Northern blot analysis, short form PRL-R mRNA was clearly detected in female rat liver and male rat kidney, and long form PRL-R mRNA was faintly observed only in female rat liver. However, the reverse transcription-polymerase chain reaction method enabled efficient analysis of mRNA levels in short and long forms of PRL-R in the liver and kidney of both male and female rats. The mRNA levels for the long and short forms of PRL-R were depressed in the liver of male rats but not in that from female rats during sexual maturation. Castration of male rats resulted in the induction of the mRNAs for these two forms of PRL-R in the liver. Testosterone, but not oestradiol, completely blocked the induction by castration of liver PRL-R gene expression. In kidney, in contrast, mRNA levels for both forms of PRL-R were depressed in female rats but not in male rats after sexual maturation. Administration of oestradiol, but not of testosterone, caused marked repression of short form PRL-R mRNA, particularly in the kidney of male rats. The levels of long form PRL-R mRNA in the kidney was less affected by the administration of oestradiol. These results have suggested that the expression of PRL-R mRNAs in rat liver and kidney is differentially regulated by testosterone and oestrogen.

Long isoform of prolactin receptor predominates in rat intrahepatic bile ducts and further increases under obstructive cholestasis

“…3B and C), at this stage PrlR expression is sex-independent in both hepatocytes and bile-duct epithelial cells. Further, in contrast to the sex differentiation of PrlR expression in hepatocytes (Sakaguchi et al 1994), in cholangiocytes the level of PrlR declines but remains sex-independent. Nevertheless, we have shown a low level of PrlR mRNA in cholangiocytes of mature male and female rats (Fig.…”

“…Female and male sex hormones act on the alternative splicing of PrlR premRNA in rat hepatocytes in a unidirectional manner: they increase the preferential inclusion of the distal exon into mature mRNA (Table 3), although with different efficacies. The effect of oestrogens on alternative splicing resulting in preferential usage of the distal exon was demonstrated for growth hormone receptor pre-mRNA in mouse hepatocytes (Talamantes & Ortiz 2002) and for PrlR pre-mRNA in rat hepatocytes (Sakaguchi et al 1994). The level of long PrlR isoforms in normal cholangiocytes is almost equal to that found in hepatocytes of male and female rats (Tables 2 and 3).…”

“…3A and B), which is also well established Table 2. (Sakaguchi et al 1994, Smirnova et al 1994, Bogorad et al 2004: male sex hormones decrease and female sex hormones increase PrlR level. In contrast, immunohistochemistry did not reveal any pronounced PrlR-positive signal in cholangiocytes (Fig.…”

“…The total level of PrlR in hepatocytes is regulated by sex hormones: oestrogens increase and androgens decrease the content of PrlR mRNA and protein (Jolicoeur et al 1989, Sakaguchi et al 1994. As in other tissues, prolactin was shown to be another positive regulator of PrlR expression in the liver (Baxter & Zaltsman 1984.…”

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

“…It has also been shown that the expression levels of PRL-R mRNA in the different brain regions are regulated by oestrogen, which increases the utilization of E1 2 and E1 3 first exons (Pi et al 2003). In the liver, the expression of the PRL-R gene is known to be regulated by sex steroid hormones; up-regulation by oestrogen and down-regulation by testosterone (Jolicoeur et al 1989, Sakaguchi et al 1994. However, the molecular mechanisms of the effects of the sex steroid hormones on the expression of the PRL-R gene in the liver are not yet known.…”