Novel genes involved in pathophysiology of gonadotropin-dependent adrenal tumors in mice

: Doroszko M, Chrusciel M, Belling K, Vuorenoja S, Dalgaard M, Leffers H, Nielsen HB, Huhtaniemi I, Toppari J, Rahman NA

Publisher: ELSEVIER IRELAND LTD

: 2017

: Molecular and Cellular Endocrinology

: MOLECULAR AND CELLULAR ENDOCRINOLOGY

: MOL CELL ENDOCRINOL

: 444

: C

: 9

: 18

: 10

: 0303-7207

DOI: https://doi.org/10.1016/j.mce.2017.01.036

Specific inbred strains and transgenic inhibin-a Simian Virus 40 T antigen (inhafrag) mice are genetically susceptible to gonadectomy-induced adrenocortical neoplasias. We identified altered gene expression in prepubertally gonadectomized (COX) inh alpha/Tag and wild-type (WT) mice. Besides earlier reported Gata4 and Lhcgr, we found up-regulated Esrl, Prlr-rsl, and down-regulated GrblO, Mrnp24, Sgcd, Rerg, Gnas, Nfatc2, Gnrhr, lgf2 in inh alpha/Tag adrenal tumors. Sex-steroidogenic enzyme genes expression (Srd5a 1, Cypl9a1) was up-regulated in tumors, but adrenal-specific steroidogenic enzyme (Cyp21al, Cyp11b1, Cypl1b2) 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 inh alpha/fag 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. Grb 10, Rerg, Gnas, and Nfatc2) in the tumors remains to be addressed. (C) 2017 Elsevier B.V. All rights reserved.