Histidine Decarboxylase as a novel therapeutic target for the treatment of Leydig cell tumors in prepubertal boys

BESIO MORENO, M.; PIGNATARO, O.P.; ABIUSO, M.; RIVAROLA, M. A.; MONDILLO, C.; ABIUSO, M.; RIVAROLA, M. A.; MONDILLO, C.; BELGOROSKY, A.; BERENSZTEIN, E.; BELGOROSKY, A.; BERENSZTEIN, E.; BESIO MORENO, M.; PIGNATARO, O.P.

Buenos Aires

Congreso; XXVI Annual Meeting of the Latin American Pediatric Endocrinology Society; 2016

Sociedad Latinoamericana de Endocrinología Pediátrica

Leydig cell tumors (LCTs) account for 1-3% of all testicular tumors in adults and 4% in prepubertal children. While usually benign, approximately 10% of LCTs in adult patients exhibit a malignant phenotype and respond poorly to chemotherapy or radiation. LCT incidence has been increasing worldwide. Although the etiology of LCTs is still unknown, several studies indicate that overexpression of CYP19 aromatase (CYP19) and excessive estrogen (E2) production play a significant role in sustaining Leydig cell tumorigenesis. Also, IGF-1 has been reported to elicit proliferative effects in rat Leydig tumor cells (LTCs) through an autocrine mechanism. Previously, we described the proliferative effect of histamine (HA) and the overexpression of histidine descarboxylase (HDC) in MA-10 LTCs. Considering that MA-10 LTCs lack 17α-hidroxylase and produce progesterone (P4) as the major steroid in response to trophic hormone and cAMP analogs, we decided to complement our former studies by evaluating the potential role of HDC in regulating the proliferation of R2C LTCs, which show constitutive CYP19 overexpression, as well as elevated E2 and IGF-1 synthesis. Furthermore, we studied HDC expression in human LCT versus normal human testis (NHT). The expression of HDC in R2C LTCs was evaluated by Western Blot and immunocytochemistry. P4 and E2 levels were determined by radioimmunoassay, and CYP19 mRNA expression was evaluated by RT-qPCR. Cell proliferation was assessed as a function of 3H-Thymidine incorporation. HDC immunoexpression was also studied in 9 NHT samples of four age groups (G): G1(neonatal, n=2), G2(infantile, n=1), G3(juvenile, n=3) and G4(pubertal, n=3), and in 3 LCT samples. We observed high HDC expression in R2C LTCs, and it significantly increased after a 24h-treatment with 100ng/ml IGF-1 (p