Supplementary Material for: Luteinizing Hormone and GATA4 Action in the Adrenocortical Tumorigenesis of Gonadectomized Female Mice Doroszko M. Chrusciel M. Stelmaszewska J. Slezak T. Rivero-Muller A. Padzik A. Anisimowicz S. Wolczynski S. Huhtaniemi I. Toppari J. Rahman N.A. 10.6084/m9.figshare.5505280.v1 https://karger.figshare.com/articles/journal_contribution/Supplementary_Material_for_Luteinizing_Hormone_and_GATA4_Action_in_the_Adrenocortical_Tumorigenesis_of_Gonadectomized_Female_Mice/5505280 <p><b><i>Background/Aims:</i></b> Physiological role of luteinizing hormone (LH) and its receptor (LHCGR) in adrenal remains unknown. In inhibin-α/Simian Virus 40 T antigen (SV40Tag) (inhα/Tag) mice, gonadectomy-induced (OVX) elevated LH triggers the growth of transcription factor GATA4 (GATA4)-positive adrenocortical tumors in a hyperplasia-adenoma-adenocarcinoma sequence. <b><i>Methods:</i></b> We investigated the role of LHCGR in tumor induction, by crossbreeding inhα/Tag with <i>Lhcgr</i> knockout (LuRKO) mice. By knocking out <i>Lhcgr</i> and <i>Gata4</i> in Cα1 adrenocortical cells (<i>Lhcgr-ko, Gata4</i>-ko) we tested their role in tumor progression. <b><i>Results:</i></b> Adrenal tumors of OVX inhα/Tag mice develop from the hyperplastic cells localized in the topmost layer of zona fasciculata. OVX inhα/Tag/LuRKO only developed SV40Tag positive hyperplastic cells that were GATA4 negative, cleaved caspase-3 positive and did not progress into adenoma. In contrast to <i>Lhcgr-ko, Gata4</i>-ko Cα1 cells presented decreased proliferation, increased apoptosis, decreased expression of <i>Inha</i>, <i>SV40Tag</i> and <i>Lhcgr</i> tumor markers, as well as up-regulated adrenal- and down-regulated sex steroid gene expression. Both <i>Gata4</i>-ko and <i>Lhcgr</i>-ko Cα1 cells had decreased expression of steroidogenic genes resulting in decreased basal progesterone production. <b><i>Conclusion:</i></b> Our data indicate that LH/LHCGR signaling is critical for the adrenal cell reprogramming by GATA4 induction prompting adenoma formation and gonadal-like phenotype of the adrenocortical tumors in inhα/Tag mice.</p> 2017-10-17 12:22:15 Lhcgr GATA4 Adrenocortical tumors Molecular mechanisms Transgenic mice