EXPRESSION OF FUNCTIONAL HISTAMINE H4 RECEPTORS IN MURINE AND HUMAN LEYDIG TUMOR CELLS.

CAROLINA MONDILLO; ADRIANA MARÍA BELÉN ABIUSO; ELBA NORA PEREYRA; MARCOS BESIO MORENO; VANINA MEDINA; MARCO AURELIO RIVAROLA; ALICIA BELGOROSKY; OMAR PEDRO PIGNATARO; ESPERANZA BERENSZTEIN

Barcelona

Congreso; 8th European Congress of Andrology; 2014

Background: Histamine is known to modulate testicular steroidogenesis through H1 and H2 receptors in Leydig cells (LC), and a recent study suggests that it may regulate LC proliferation under pathological conditions. The H4 receptor (H4R), discovered thirteen years ago, is considered a promising drug target for allergy, inflammation, autoimmune disorders and cancer. Although there is indirect evidence of its presence within the testis, neither its specific localization nor its role has been established. Aim: To examine H4R expression and function in LC. Methods: We assessed H4R expression in MA-10 Leydig tumor cells (LTC) by immunofluorescence, and evaluated the effects of two H4R agonists on steroidogenesis and proliferation. We also studied H4R immunoexpression in eleven normal human (h) testes of four age groups (Gr): Gr1(neonatal,n=2), Gr2(postnatal activation,n=4), Gr3(pre-pubertal,n=3) and Gr4(pubertal,n=2), and in two hLC tumors (3.92 and 6.0 years-old). Results: We found that MA-10 LTC express H4R, and that its activation leads to inhibition of LH/hCG-induced cAMP production, StAR expression and steroid synthesis. Moreover, we observed decreased MA-10 cell proliferation after a 24-hour H4R agonist treatment. We also found H4R to be expressed in R2C LTC. Finally, We detected H4R in 2/2 hLC tumors, but only in hLC of 3 normal testes, corresponding to Gr1, Gr2, and Gr4. No H4R was found in other testicular cells. Conclusion: This study constitutes the first important step into understanding the physiological and/or pathological significance of H4R expression within the testis, and should be taken into consideration in the rational design of H4R agonists for therapeutic purposes.