Chronic treatment with sildenafil stimulates Leydig cell and testosterone secretion

Int J Exp Pathol. 2009 Aug;90(4):454-62. doi: 10.1111/j.1365-2613.2009.00660.x.


The phosphodiesterase type 5 (PDE5) inhibitor, Sildenafil, is a novel, oral treatment approach for pulmonary hypertension. As Leydig cells present PDE5, this study was conducted to investigate the effects of the chronic treatment with Sildenafil (25 mg/kg) on male Swiss Webster mice steroidogenesis. After a 4-week long experimental design, Leydig cells were analysed by morphological and immunocytochemical procedures. Serum testosterone was assayed by radioimmunoassay. Leydig cells presented noteworthy ultrastructural alterations, such as a vesicular smooth endoplasmic reticulum, large vacuoles scattered through the cytoplasm, enlarged mitochondria with discontinue cristaes and whorle membranes with vesicles at the periphery, which are typical characteristics of an activated steroid-secreting cell. Important immunocytochemical labelling for steroidogenic acute regulatory protein, cytochrome P450 side-chain cleavage enzyme and testosterone were detected in isolated Leydig cells. In addition, Sildenafil-treated mice showed significant increased levels of total testosterone. The results obtained in the present study are consistent with the hypothesis that the accumulation of cyclic guanosine monophosphate by PDE5 inhibition could be involved in the androgen biosynthesis stimulation. Important clinical implications of hormonal disorders should be taken into account for patients with pulmonary hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cholesterol Side-Chain Cleavage Enzyme / analysis
  • Immunohistochemistry
  • Leydig Cells / drug effects
  • Leydig Cells / metabolism*
  • Leydig Cells / ultrastructure
  • Male
  • Mice
  • Mice, Inbred Strains
  • Microscopy, Electron, Transmission
  • Phosphodiesterase 5 Inhibitors*
  • Phosphoproteins / analysis
  • Piperazines / pharmacology*
  • Purines / pharmacology
  • Sildenafil Citrate
  • Stimulation, Chemical
  • Sulfones / pharmacology*
  • Testosterone / analysis
  • Testosterone / biosynthesis*
  • Testosterone / blood
  • Vasodilator Agents / pharmacology*


  • Phosphodiesterase 5 Inhibitors
  • Phosphoproteins
  • Piperazines
  • Purines
  • Sulfones
  • Vasodilator Agents
  • steroidogenic acute regulatory protein
  • Testosterone
  • Sildenafil Citrate
  • Cholesterol Side-Chain Cleavage Enzyme