Exposure to phosphodiesterase type 5 inhibitors stimulates aromatase expression in human adipocytes in vitro

Antonio Aversa, Massimiliano Caprio, Antonella Antelmi, Andrea Armani, Marina Brama, Emanuela A. Greco, Davide Francomano, Matilde Calanchini, Giovanni Spera, Luigi Di Luigi, Giuseppe M C Rosano, Andrea Lenzi, Silvia Migliaccio, Andrea Fabbri

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Abstract

Introduction. Prolonged tadalafil administration in men with erectile dysfunction is associated with increased testosterone (T): estradiol (E2) ratio mainly related to reduction of E2 levels. Aim. To investigate the presence of phosphodiesterase type 5 (PDE5) isoenzyme in primary human visceral adipocytes and whether different PDE5 inhibitors (PDE5i) could directly modulate aromatase (ARO) expression in differentiated human visceral adipocytes in culture. Main Outcome Measures. PDE5 mRNA and protein expression in primary human visceral adipocytes as well as mRNA and protein expression of ARO, with functional activity after selective PDE5 blockade by tadalafil and sildenafil. Methods. Purified primary human visceral pre-adipocytes were differentiated ex vivo and were exposed to tadalafil or sildenafil (1μM) for different intervals of time (6-12-24-96 hours). ARO mRNA content and expression were measured by Western Blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. T and E2 in supernatants were measured by ELISA also in the presence of letrozole. Results. Differentiated adipocytes were found to express detectable levels of PDE5 transcripts. Acute exposure (6 hours) to both PDE5i tadalafil and sildenafil increased ARO mRNA expression by 4.7- and 2.8-fold, respectively (P2 concentrations in the supernatant (1.7 and 2 fold, respectively; P

Original languageEnglish
Pages (from-to)696-704
Number of pages9
JournalJournal of Sexual Medicine
Volume8
Issue number3
DOIs
Publication statusPublished - Mar 2011

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Keywords

  • CYP19
  • Endothelial Health
  • Estradiol
  • Human Visceral Adipocytes
  • Nitric Oxide
  • PDE5 Inhibitors
  • Sildenafil
  • Tadalafil

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Aversa, A., Caprio, M., Antelmi, A., Armani, A., Brama, M., Greco, E. A., Francomano, D., Calanchini, M., Spera, G., Luigi, L. D., Rosano, G. M. C., Lenzi, A., Migliaccio, S., & Fabbri, A. (2011). Exposure to phosphodiesterase type 5 inhibitors stimulates aromatase expression in human adipocytes in vitro. Journal of Sexual Medicine, 8(3), 696-704. https://doi.org/10.1111/j.1743-6109.2010.02152.x