EN CÉLULAS MUSCULARES ESQUELÉTICAS EL 17b-ESTRADIOL Y EL CALCITRIOL REGULAN LA EXPRESIÓN DE LA ONCOPROTEÍNA C-FOS A TRAVÉS DE LAS CASCADAS MAPKs”

RONDA A C; BUITRAGO C; BOLAND R

Rosario, Argentina

Congreso; XXIII Reunion Annual Asociación Argentina de Osteología y Metabolismo Mineral (AAOMM); 2006

The C2C12 skeletal muscle cell line expresses 1α,25(OH)2-vitamin D3 (calcitriol) and 17b-estradiol (estradiol) receptors but the actions of these steroid hormones are unclear. In various tissues, calcitriol and estradiol promote responses through mitogen activated protein kinases (MAPKs). We have previously shown that calcitriol rapidly activates p38 MAPK and stimulates muscle cell proliferation via extracellular regulated kinases (ERKs) 1/2. In the present work, immunoblot analysis using phosphospecific antibodies revealed that estradiol also activates ERK1/2 and p38 MAPK in a time-dependent manner faster than calcitriol. The involvement of Src kinases in calcitriol-mediated MAPKs stimulation was demonstrated using the specific inhibitor PP1. Moreover, in cells transfected with a c-Src antisense probe, the effects of calcitriol on p38 MAPK phosphorylation were reduced. Studies are undergoing to ascertain whether Src also participates in estradiol activation of MAPKs. Modulation of gene expression upon stimulation of MAPKs by the two hormones was investigated. Both calcitriol and estradiol induced ERK1/2-dependent phosphorylation of Elk-1 and CREB transcription factors. Of relevance, Elk-1 phosphorylation by either hormone was correlated with c-fos oncoprotein increased expression. In addition, treatment of cells with estradiol but not calcitriol, increased c-jun protein levels. Summarizing, both hormones activate through MAPK pathways the expression of early genes with key roles in muscle cell proliferation. This mechanism may help to understand myopathies characterized by alterations in contractility and atrophy in calcitriol deficit states and muscular weakness in post menopause women without hormonal replacement therapy.