Regulation of phosphodiesterase 5 expression and activity in human pregnant and non-pregnant myometrial cells by human chorionic gonadotropin.
OBJECTIVE
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.
Belmonte
Alessia
A
Department of Surgery, University Tor Vergata, Rome, Italy.
Ticconi
Carlo
C
Dolci
Susanna
S
Giorgi
Mauro
M
Zicari
Alessandra
A
Lenzi
Andrea
A
Jannini
Emmanuele A
EA
Piccione
Emilio
E
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007743:Labor, Obstetric; D009119:Muscle Contraction / Q000187:drug effects*; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones
D006063:Chorionic Gonadotropin; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D003994:Bucladesine; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D006152:Cyclic GMP