CONICET | Buscador de Institutos y Recursos Humanos

Curcumin and heme oxygenase-1effects on Leydig cells steroidogenesis and proliferation.Raices T1, Varela ML1,Besio Moreno M1, Pereyra EN1, Pignataro OP1,2.1 Institute of Biology and Experimental Medicine(IBYME-CONICET). 2 Department of Biological Chemistry, School ofSciences, University of Buenos Aires. E-mail: triniraices@hotmail.com Curcumin (CUR) or diferuloylmethane is a bioactivecomponent of turmeric, a food additive derived from the rhizome of the plant Curcuma longa. This dietary polyphenol isthe subject of countless studies since it has proven to have both prophylacticand therapeutic effects on illnesses as diverse as cancer, diabetes,cardiomyopathies, chronic pain and neurodegenerative diseases. One of itsmechanisms of action is the activation of antioxidant pathways. Given thatthere is not much information about how it affects the endocrine population ofthe testis, the Leydig cells (LCs), we aimed to describe CUR effects on MA-10tumoral cell line steroidogenesis and proliferation. On the other hand, wesought to clarify its interaction with one of the most important antioxidantenzymes, heme oxygenase-1 (HO-1). After a 5-h incubation with growingconcentrations of CUR, we assessed progesterone production by radioimmunoassayand found that CUR stimulates LCs steroidogenesis at 20-40 µM concentrationsand inhibits steroidogenesis at 80-100 µM. This inhibition correlates with amarked alteration of cell morphology and a significant decrease in cellviability as evaluated by trypan blue exclusion assay. Secondly, cellproliferation was assessed after a 24-h incubation period using the sulphorhodamineB assay. CUR has a positive effect at 20 µM concentration and decreasesproliferation at 80-100 µM. We have previously described HO-1 negative effecton MA-10 steroidogenesis and proliferation. Cells were incubated for 5 h withCUR and subjected to Western blot assay. CUR augments basal HO-1 protein levelsin a concentration dependent fashion. CUR also enhances HO-1 expression whenstimulated with hemin, its inducer. What?s more, if LCs are preincubated for 1h with CUR and then subjected to a 5-h incubation with hemin, CUR can partiallyrevert HEM negative effect on steroidogenesis provided that hemin does not induceHO-1 to such extent that it completely abrogates steroidogenesis regulation.The results presented herein contribute to the understanding on how curcuminregulates MA-10 cells functions and how it can impair them if present in highconcentrations. Besides, we show that depending on how strong the stimuliupregulating HO-1 expression is, CUR can act as a protective agent revertingthe negative effect of this enzyme on steroidogenesis.