title: Transient rise of serum testosterone level after single sildenafil treatment of adult male rats.
abstract: BACKGROUND
  Phosphodiesterase type 5 (PDE5) inhibitors have been established in therapy for a variety of physiological disorders including erectile dysfunction. Despite its popularity and wide usage in erectile dysfunction treatment, the short-term effect of PDE5 inhibition on Leydig cell functionality and testosterone dynamics is missing.
  
  
  OBJECTIVE
  This study was designed to assess the acute in vivo effects of sildenafil citrate (Viagra) treatment on testosterone production.
  
  
  METHODS
  Male adult rats were given sildenafil (1.25 mg/kg BW) per os, and testosterone production were analyzed 30, 60, 120, and 180 minutes after treatment. Additionally, in vitro effect of sildenafil extract on Leydig cell steroidogenesis was estimated.
  
  
  METHODS
  The formation of testicular interstitial fluid (TIF), and testosterone, cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP) content was followed. Occurrence and phosphorylation of mature steroidogenic acute regulatory protein (StAR) and interaction with protein kinase G 1 (PRKG1) were assessed by immunoprecipitation and Western blot.
  
  
  RESULTS
  Serum testosterone was increased 60 and 120 minutes after sildenafil treatment. In 60 minutes, TIF volume was doubled and stayed increased till the end of the experimental period. cGMP and testosterone content in TIF were increased 30 minutes after treatment, and cAMP decreased in 60 minutes. Further, sildenafil-induced stimulation of testosterone production was abolished by ex vivo addition of PRKG1 inhibitor but not by protein kinase A inhibitor. Sildenafil treatment increased the level of phosphorylated and total StAR protein. Moreover, co-immunoprecipitation of StAR and PRKG1 was increased following sildenafil treatment suggesting the active role of this kinase in initiation of testosterone synthesis. Additionally, sildenafil extract applied in vitro on primary Leydig cell culture increased cGMP accumulation and testosterone production in time- and dose-dependent manner without effect on cAMP level.
  
  
  CONCLUSIONS
  Acute sildenafil treatment enlarged TIF volume but also stimulated testosterone production which may be significant considering the positive testosterone effect in regulation of sexual activity.
authors.affiliation: Reproductive Endocrinology and Signaling Group, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
authors.forename: Marija M
authors.initials: MM
authors.lastname: Janjic
authors.forename: Natasa J
authors.initials: NJ
authors.lastname: Stojkov
authors.forename: Maja M
authors.initials: MM
authors.lastname: Bjelic
authors.forename: Aleksandar I
authors.initials: AI
authors.lastname: Mihajlovic
authors.forename: Silvana A
authors.initials: SA
authors.lastname: Andric
authors.forename: Tatjana S
authors.initials: TS
authors.lastname: Kostic
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D047468:Immunoprecipitation; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D013737:Testis / Q000378:metabolism*; D013739:Testosterone / Q000097:blood*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010750:Phosphoproteins; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D000068677:Sildenafil Citrate; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP