CALCITRIOL AS A POTENTIAL THERAPEUTIC OPTION FOR THE TREATMENT OF LEYDIG CELL TUMORS

ABIUSO, ADRIANA MARÍA BELÉN; BELGOROSKY, ALICIA; VARELA, MARÍA LUISA; PIGNATARO OMAR P; MONDILLO CAROLINA; BESIO MORENO MARCOS; BERENSZTEIN, ESPERANZA

Florianopolis

Congreso; SLEP 2019; 2019

Sociedad Lationoamericana de Endocrinología Pediátrica

CALCITRIOL AS A POTENTIAL THERAPEUTIC OPTION FOR THE TREATMENT OF LEYDIG CELL TUMORSVARELA, María Luisa1; ABIUSO, Adriana María Belén1; BESIO MORENO, Marcos1; PIGNATARO, Omar Pedro1; BELGOROSKY, Alicia2; BERENSZTEIN, Esperanza2 MONDILLO, Carolina1.1.Laboratorio de Endocrinología Molecular y Transducción de Señales, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490 (C1428ADN), Buenos Aires, Argentina.2.Servicio de Endocrinología, Hospital de Pediatría ?Prof. Dr. Juan P. Garrahan?, Buenos Aires, Argentina. Vitamin D (VD) is a steroid hormone with key roles in human health. Its main biologically active form, 1α,25-dihydroxy-vitamin D3 (calcitriol, CAL), binds to a specific receptor exhibiting ubiquitous tissue expression, the VD receptor (VDR). Besides influencing calcium and phosphate homeostasis, VD regulates immunity, angiogenesis and growth, differentiation and apoptosis in many cell types, including malignant cells. Leydig cell tumors (LCT) are endocrine tumors of the testis, with increased incidence recently reported. Although mostly benign, LCT are associated with precocious puberty in children and a wide variety of hormonal manifestations in adults. Importantly, malignant LCT are unresponsive to chemo or radiotherapy. These facts highlight the need to increase our knowledge about LCT, to find new therapeutic options. Although CAL treatment has been described as effective in several tumor types, little is known about its potential as a therapeutic drug in LCT. Objectives: To study the effect of CAL on tumor Leydig cell proliferation in vitro and LCT growth in vivo. To evaluate the expression of VDR in testis sections of prepubertal patients with different testicular pathologies (LCT, Leydig cell hyperplasia, germ cell tumor or Sertoli cell tumor). Methods: In in vitro experiments, tumor Leydig cell lines R2C and MA-10 were treated with CAL (10-11M to 10-8 M) for 48 hours, after which cell proliferation was determined using Sulforhodamine B assay. Murine LCT models were developed by subcutaneously injecting R2C and MA-10 cells into athymic mice and C57 x BALB/c offspring (F1), respectively. CAL treatment (0,05 µg) was administered thrice a week for 15 days. Tumor size was measured using a digital caliber. Formalin-fixed, paraffin-embedded human sample sections were tested for VDR expression using immunohistochemistry. The study was approved by the Ethical Committee of Hospital de Pediatría Garrahan.Results: Both R2C and MA-10 cells showed decreased proliferation after treatment with CAL at 10-9 M and 10-11 M in vitro (p