EFFECTS OF 17-BETA-ESTRADIOL AND PROGESTERONE ON MITOGEN-ACTIVATED PROTEIN-KINASE EXPRESSION AND ACTIVITY IN RAT UTERINE SMOOTH-MUSCLE

Activation of mitogen-activated protein kinases (MAPKs) is a critical event in mitogenic signal transduction. MAPKs are activated by tyrosin e phosphorylation and translocate to different cellular compartments a ffecting protein function and gene expression. MAPK expression and act ivity was examined in uterine smooth muscle from rats pretreated with estradiol-17 beta alone or with estradiol-17 beta and progesterone. MA PK expression was detected by immunoblotting using erk1/2 antibodies. MAPK activity was detected by measurement of the phosphorylation of a MAPK-specific peptide sequence of myelin basic protein. Steroid treatm ent caused a modest (20%) decline in erk 1 and 2 expression in membran e and cytosolic fractions. Both estrogen and progesterone increased MA PK tyrosine phosphorylation and membrane-associated MAPK activity. Ste roid treatment increased cytosolic MAPK tyrosine phosphorylation, but not enzymatic activity. These data suggest that gonadal steroid hormon es, which stimulate uterine hypertrophy, may exert their hypertrophic effects by increasing MAPK activity.