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

J Soc Gynecol Investig. 2005 Dec;12(8):570-7. doi: 10.1016/j.jsgi.2005.09.002.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / pharmacology
  • Bucladesine / pharmacology*
  • Cells, Cultured
  • Chorionic Gonadotropin / pharmacology*
  • Cyclic GMP / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Humans
  • Immunohistochemistry
  • Labor, Obstetric
  • Muscle Contraction / drug effects*
  • Myometrium / drug effects*
  • Myometrium / metabolism
  • Myometrium / ultrastructure
  • Phosphoric Diester Hydrolases / genetics
  • Phosphoric Diester Hydrolases / metabolism*
  • Piperazines / pharmacology
  • Pregnancy
  • Purines
  • Sildenafil Citrate
  • Sulfones

Substances

  • Chorionic Gonadotropin
  • Piperazines
  • Purines
  • Sulfones
  • Bucladesine
  • Sildenafil Citrate
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human
  • Cyclic GMP