title: 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 whole-body 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' 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, hE1N2, which was also principally transcribed in the kidneys and small intestines, and an exon hE1N3 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.
authors.affiliation: Department of Animal ScienceGenome CenterUniversity of California Davis, 2335 Meyer Hall, One Shields Avenue, Davis, California 95616, USABaylor College of MedicineUSDA/ARS Children's Nutrition Research Center, 1100 Bates Street, Room 9022, Houston, Texas, USAUSDAARS, U.S. Meat Animal Research Center, PO Box 166, Clay Center, Nebraska 68933, USA.
authors.forename: Anke
authors.initials: A
authors.lastname: Schennink
authors.affiliation: Department of Animal ScienceGenome CenterUniversity of California Davis, 2335 Meyer Hall, One Shields Avenue, Davis, California 95616, USABaylor College of MedicineUSDA/ARS Children's Nutrition Research Center, 1100 Bates Street, Room 9022, Houston, Texas, USAUSDAARS, U.S. Meat Animal Research Center, PO Box 166, Clay Center, Nebraska 68933, USA jftrott@ucdavis.edu.
authors.forename: Josephine F
authors.initials: JF
authors.lastname: Trott
authors.affiliation: Department of Animal ScienceGenome CenterUniversity of California Davis, 2335 Meyer Hall, One Shields Avenue, Davis, California 95616, USABaylor College of MedicineUSDA/ARS Children's Nutrition Research Center, 1100 Bates Street, Room 9022, Houston, Texas, USAUSDAARS, U.S. Meat Animal Research Center, PO Box 166, Clay Center, Nebraska 68933, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Manjarin
authors.affiliation: Department of Animal ScienceGenome CenterUniversity of California Davis, 2335 Meyer Hall, One Shields Avenue, Davis, California 95616, USABaylor College of MedicineUSDA/ARS Children's Nutrition Research Center, 1100 Bates Street, Room 9022, Houston, Texas, USAUSDAARS, U.S. Meat Animal Research Center, PO Box 166, Clay Center, Nebraska 68933, USA.
authors.forename: Danielle G
authors.initials: DG
authors.lastname: Lemay
authors.affiliation: Department of Animal ScienceGenome CenterUniversity of California Davis, 2335 Meyer Hall, One Shields Avenue, Davis, California 95616, USABaylor College of MedicineUSDA/ARS Children's Nutrition Research Center, 1100 Bates Street, Room 9022, Houston, Texas, USAUSDAARS, U.S. Meat Animal Research Center, PO Box 166, Clay Center, Nebraska 68933, USA.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Freking
authors.affiliation: Department of Animal ScienceGenome CenterUniversity of California Davis, 2335 Meyer Hall, One Shields Avenue, Davis, California 95616, USABaylor College of MedicineUSDA/ARS Children's Nutrition Research Center, 1100 Bates Street, Room 9022, Houston, Texas, USAUSDAARS, U.S. Meat Animal Research Center, PO Box 166, Clay Center, Nebraska 68933, USA.
authors.forename: Russell C
authors.initials: RC
authors.lastname: Hovey
mesh_terms: D000818:Animals; D001483:Base Sequence; D002645:Chickens; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D023281:Genomics; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011981:Receptors, Prolactin / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D034421:Sus scrofa / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D011981:Receptors, Prolactin
keywords: gene regulation; kidney; prolactin; receptor; transcription factors