title: Novel genes involved in pathophysiology of gonadotropin-dependent adrenal tumors in mice.
abstract: Specific inbred strains and transgenic inhibin-α Simian Virus 40 T antigen (inhα/Tag) mice are genetically susceptible to gonadectomy-induced adrenocortical neoplasias. We identified altered gene expression in prepubertally gonadectomized (GDX) inhα/Tag and wild-type (WT) mice. Besides earlier reported Gata4 and Lhcgr, we found up-regulated Esr1, Prlr-rs1, and down-regulated Grb10, Mmp24, Sgcd, Rerg, Gnas, Nfatc2, Gnrhr, Igf2 in inhα/Tag adrenal tumors. Sex-steroidogenic enzyme genes expression (Srd5a1, Cyp19a1) was up-regulated in tumors, but adrenal-specific steroidogenic enzyme (Cyp21a1, Cyp11b1, Cyp11b2) down-regulated. We localized novel Lhcgr transcripts in adrenal cortex parenchyma and in non-steroidogenic A cells, in GDX WT and in intact WT mice. We identified up-regulated Esr1 as a potential novel biomarker of gonadectomy-induced adrenocortical tumors in inhα/Tag mice presenting with an inverted adrenal-to-gonadal steroidogenic gene expression profile. A putative normal adrenal remodeling or tumor suppressor role of the down-regulated genes (e.g. Grb10, Rerg, Gnas, and Nfatc2) in the tumors remains to be addressed.
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Finland.
authors.forename: Milena
authors.initials: M
authors.lastname: Doroszko
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Finland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Chrusciel
authors.affiliation: DTU Multi-Assay Core, Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Belling
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Vuorenoja
authors.affiliation: DTU Multi-Assay Core, Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Marlene
authors.initials: M
authors.lastname: Dalgaard
authors.affiliation: DTU Multi-Assay Core, Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Leffers
authors.affiliation: DTU Multi-Assay Core, Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: H Bjørn
authors.initials: HB
authors.lastname: Nielsen
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Finland; Institute of Reproductive and Developmental Biology, Imperial College London, London, UK.
authors.forename: Ilpo
authors.initials: I
authors.lastname: Huhtaniemi
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Finland; Department of Pediatrics, Turku University Hospital, Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Toppari
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Finland; Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Poland. Electronic address: nafis.rahman@utu.fi.
authors.forename: Nafis A
authors.initials: NA
authors.lastname: Rahman
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D050980:GATA Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D063990:Gene Ontology; D052138:Genes, Neoplasm; D006062:Gonadotropins / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D013256:Steroids / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D050980:GATA Transcription Factors; D006062:Gonadotropins; D013256:Steroids
keywords: Adrenal tumor; Biomarker; GATA4; Gonadotropin; LHCGR; Pathophysiology