Vitamin D modifies steroidogenesis and regulates the expression of components of the histaminergic system in tumoral Leydig cells

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

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencia; 2017

Sociedad Argentina de Investigación Clínica

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