Comparative genomics reveals tissue-specific regulation of prolactin receptor gene expression

Abstract

Prolactin (PRL), acting via the PRL receptor (PRLR), controls hundreds of biological processes across a range of species. Endocrine PRL elicits well-documented effects on target tissues such as the mammary glands and reproductive organs in addition to coordinating wholebody homeostasis during states such as lactation or adaptive responses to the environment. While changes in PRLR expression likely facilitates these tissue-specific responses to circulating PRL, the mechanisms regulating this regulation in non-rodent species has received limited attention. We performed a wide-scale analysis of PRLR 5 0 transcriptional regulation in pig tissues. Apart from the abundantly expressed and widely conserved exon 1, we identified alternative splicing of transcripts from an additional nine first exons of the porcine PRLR (pPRLR) gene. Notably, exon 1.5 transcripts were expressed most abundantly in the heart, while expression of exon 1.3-containing transcripts was greatest in the kidneys and small intestine. Expression of exon 1.3 mRNAs within the kidneys was most abundant in the renal cortex, and increased during gestation. A comparative analysis revealed a human homologue to exon 1.3, hE1 N2 , which was also principally transcribed in the kidneys and small intestines, and an exon hE1 N3 was only expressed in the kidneys of humans. Promoter alignment revealed conserved motifs within the proximal promoter upstream of exon 1.3, including putative binding sites for hepatocyte nuclear factor-1 and Sp1. Together, these results highlight the diverse, conserved and tissue-specific regulation of PRLR expression in the targets for PRL, which may function to coordinate complex physiological states such as lactation and osmoregulation.

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

“…For example, in addition to the abundantly expressed and widely conserved exon 1 among different species, the PRLR gene has multiple additional first exons because of alternative splicing in different tissues (52). Different tissues can have different 5Ј-regions of the Prlr gene (53).…”

“…It remains to be determined whether Zfhx3 directly binds to Prlr promoter, and if so where it binds. Porcine Prlr promoter, which is the best studied so far among different species for the potential use of Prlr as a marker for reproductive performance (56 -59), has 12 alternative first exons (52). Similar to porcine Prlr, the 5Ј region of mouse Prlr is also quite large, spanning more than 120 kb (Fig.…”

Gene expression levels of the insulin-like growth factor family in patients with AMD before and after ranibizumab intravitreal injections

“…Some reports revealed that it can play an antiapoptotic role and that it can stimulate angiogenesis, but other reports showed that IGFBP3 could inhibit angiogenesis and counteract the effect of VEGF. 27 Although an increased level of IGF1 in vitreous proliferative diabetic retinopathy is seen, the IGFBP1 and IGFBP3 levels were unchanged. 57 In turn, infants with ROP had a lower plasma IGFBP3 level.…”

“… 51 Some of these proteins can act through IGF-independent mechanisms. 27 Moreover, retinas in a hypoxia condition showed a decreased expression of IGFBP7 compared to retinas in a normal condition. 13 Lofqvist et al 59 detected a greater expression of IGF2 than IGF1 in the photoreceptors and blood vessels of mouse retina.…”

“…The IGF family plays an important role in the pathogenesis of many diseases, including eye diseases. 27 Lambooij et al 28 and Rosenthal et al 29 suggested its implication in the development of AMD. However, the exact role of IGFs in AMD still needs to be explained.…”