VITAMIN D REGULATES STEROIDOGENESIS AND INFLUENCES THE EXPRESSION OF SEVERAL COMPONENTS OF THE HISTAMINERGIC SYSTEM IN R2C TUMOR LEYDIG CELLS

SUÁREZ SEBASTIÁN; BESIO MORENO MARCOS; CONSTANZO PABLO; PIGNATARO OMAR P; VARELA, MARÍA LUISA; MONDILLO CAROLINA; KNOBLOVITS PABLO; ABIUSO, ADRIANA MARÍA BELÉN

Buenos Aires

Congreso; LXII Reunión Científica de la Sociedad Argentina de Investigación Clínica; 2017

SAIC

(515) VITAMIN D REGULATES STEROIDOGENESIS AND INFLUENCES THE EXPRESSION OF SEVERAL COMPONENTS OF THE HISTAMINERGIC SYSTEM IN R2C TUMOR LEYDIG CELLS. María Luisa Varela (1), Adriana María Belén Abiuso (1), Marcos Besio Moreno (1), Omar Pedro Pignataro (1), Pablo Knoblovits (2), Sebastián Suárez (2), Pablo René Costanzo (2), Carolina Mondillo (1) (1) Laboratorio de Endocrinología Molecular y Transducción de Señales, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina. (2) Servicio de Endocrinología, Metabolismo y Medicina Nuclear, Hospital Italiano de Buenos Aires. C.A.B.A., Argentina. Leydig cell tumors (LCT) are endocrine tumors of the testicular interstitium. Current evidence indicates that aromatase (CYP19) overexpression and excessive estrogen (E2) production play a crucial part in their genesis. Although most LCT are benign, malignant LCT respond poorly to chemo/radiotherapy, underscoring the importance of developing novel therapeutic strategies. Bioactive vitamin D (calcitriol; CAL) is a steroid hormone with a major role in human health. CAL binds to nuclear vitamin D receptor (VDR), a ligand-inducible transcription factor that functions to control target gene expression. Vitamin D deficiency has been linked to various malignancies, including cancer. Previously, we reported that histamine (HA) is an autocrine growth factor in LCT. Also, we detected VDR in human Leydig cell (LC) hyperplasia and LCT. Several components of the HA-ergic system are targets of VDR, and CAL regulates CYP19 in many cell types. Thus, to assess the question whether CAL plays a role in LCT, we studied its ability to modulate the expression of genes involved in maintaining the tumor phenotype. Experiments were performed in R2C LC (R2C), the best known in vitro model for Leydigioma. R2C were treated with CAL (10-11 M-10-8 M). Gene and protein expression were evaluated by RT-qPCR and Western blot, respectively. Cell proliferation was measured by 3H-Thymidine incorporation. CAL (10-9 M; 5 h) increased the expression of VDR, histidine decarboxylase (HDC) and HA receptors H1 and H4 genes (p