Regulation of phosphodiesterase 5 expression and activity in human pregnant and non-pregnant myometrial cells by human chorionic gonadotropin.

OBJECTIVES: This study has a twofold aim: 1) to investigate whether protein expression and enzyme activity of phosphodiesterase 5 (PDE5) can be detected in human myometrium and undergo changes in relation to the presence of pregnancy and/or labor; 2) to evaluate whether PDE5 expression and activity in myometrial cells can be influenced by human chorionic gonadotropin (HCG).

METHODS: Primary cultures of myometrial cells, obtained from non-pregnant women and from pregnant women at term, either before or during labor, were carried out in the presence of HCG or dibutyryl-cyclic AMP (db-cAMP), the non-hydrolizable analogue of cAMP. PDE5 expression in cultures of myometrial cells was detected by immunocytochemistry and western blot. PDE5 activity was detected in cell extracts by enzyme assay.

RESULTS: PDE5 is expressed and is functionally active in smooth muscle cells. Treatment of cell cultures with HCG and db-cAMP results in a reduction of PDE5 expression and activity. The effects of HCG and db-cAMP are exerted irrespective of the functional status of the myometrium (non-pregnant, pregnant not in labor, pregnant in labor).

CONCLUSIONS: PDE5 protein is expressed in human non-pregnant and pregnant myometrium. HCG reduces PDE5 expression and enzyme activity in smooth muscle cells, possibly through a pathway involving cAMP.