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Journal of the Society for Gynecologic Investigation
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Regulation of Phosphodiesterase 5 Expression and Activity in Human Pregnant and Non-pregnant Myometrial Cells by Human Chorionic Gonadotropin

Alessia Belmonte, MD

Department of Surgery, Section of Gynecology and Obstetrics, University Tor Vergata, Rome; Department of Public Health and Cellular Biology, Section of Anatomy, University Tor Vergata, Rome; Department of Experimental Medicine, Section of Medical Sexology, University of L'Aquila, L'Aquila; Department of Basic and Applied Biology, Section of Physiology, University of L'Aquila, L'Aquila; Department of Medical Pathophysiology, Section of Endocrinology, University La Sapienza, Rome; Department of Experimental Medicine, University La Sapienza, Rome, Italy

Carlo Ticconi, MD

Department of Surgery, Section of Gynecology and Obstetrics, University Tor Vergata, Rome; Department of Public Health and Cellular Biology, Section of Anatomy, University Tor Vergata, Rome; Department of Experimental Medicine, Section of Medical Sexology, University of L'Aquila, L'Aquila; Department of Basic and Applied Biology, Section of Physiology, University of L'Aquila, L'Aquila; Department of Medical Pathophysiology, Section of Endocrinology, University La Sapienza, Rome; Department of Experimental Medicine, University La Sapienza, Rome, Italy; ticconi{at}med.uniroma2.it

Susanna Dolci, PhD

Mauro Giorgi, PhD

Alessandra Zicari, MD

Andrea Lenzi, MD

Emmanuele A. Jannini, MD

Emilio Piccione, MD

Department of Surgery, Section of Gynecology and Obstetrics, University Tor Vergata, Rome; Department of Public Health and Cellular Biology, Section of Anatomy, University Tor Vergata, Rome; Department of Experimental Medicine, Section of Medical Sexology, University of L'Aquila, L'Aquila; Department of Basic and Applied Biology, Section of Physiology, University of L'Aquila, L'Aquila; Department of Medical Pathophysiology, Section of Endocrinology, University La Sapienza, Rome; Department of Experimental Medicine, University La Sapienza, Rome, Italy

Objectives: This study has a twofold aim: 1) to investigate whether protein expression and enzyme activity of phosphodiesterase 4 (PDE5) can be detected in human myometrium and undergo changes in relation to the presence of pregnancy and/or labor; 2) to evaluate whether PDE 5 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 tem, either before or during labor, were carried out in the presence of HCG or dibutyryl-cyclic AMP (ad-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 myscle 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 (n0n-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

Key Words: Phosphodiesterase 5 • human chorionic gonadotropin • myometrium • pregnance • labor

Journal of the Society for Gynecologic Investigation, Vol. 12, No. 8, 570-577 (2005)
DOI: 10.1016/j.jsgi.2005.09.002
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