title: Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome.
abstract: BACKGROUND
  Metabolic syndrome (MetS) is a clustering of cardio-metabolic risk factors (hyperglycemia, hypertension, dyslipidemia, visceral fat accumulation) that is also associated with hypogonadism and erectile dysfunction (ED).
  
  
  OBJECTIVE
  To clarify the relationships among MetS, hypogonadism, and ED, we developed an animal model of MetS.
  
  
  METHODS
  Male rabbits fed a high-fat diet (HFD), with or without testosterone (T) supplementation, were compared with control rabbits (fed a standard chow) and with rabbits made hypogonadal by a single injection of a long-acting GnRH-analog, triptorelin.
  
  
  METHODS
  Evaluation of metabolic disturbances (plasma glucose, cholesterol, triglycerides, testosterone, LH, FSH level, glucose tolerance, mean arterial pressure, visceral fat accumulation), and corpora cavernosa (CC) relaxant capacity (in vitro contractility study) in HFD animals as compared with control, GnRH analog-treated rabbits, and T-supplemented HFD rabbits.
  
  
  RESULTS
  HFD rabbits showed all the features of MetS. HFD induced hypogonadotropic hypogonadism is characterized by a reduction of plasma T, FSH, LH levels, testis and seminal vesicles weight, and testicular steroidogenic enzymes. Such a phenotype is similar to that induced by triptorelin administration. A reduced GnRH immunopositivity in hypothalamus suggests a central origin of HFD-related hypogonadism. HFD also induced penile alterations, as demonstrated by a reduction of acetylcholine-and electrical field stimulation-induced CC relaxation, hyper-responsiveness to the NO donor, SNP, and unresponsiveness to PDE5 inhibitors. Similar penile alterations were observed in triptorelin treated rabbit. In HFD, as well as in triptorelin treated rabbits, PDE5 and eNOS mRNA expression quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) were significantly decreased. T administration prevented almost all penile alterations observed in HFD rabbits. T treatment dramatically reduced HFD-induced visceral obesity, partially ameliorating also the metabolic profile.
  
  
  CONCLUSIONS
  We have developed an animal model of MetS associated with hypogonadotropic hypogonadism and penile alterations including unresponsiveness to PDE5 inhibitors. T supplementation was able to partially revert HFD-induced phenotype.
authors.affiliation: University of Florence Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction- Departments of Pharmacology and Clinical Physiopathology, Florence, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Filippi
authors.forename: Linda
authors.initials: L
authors.lastname: Vignozzi
authors.forename: Annamaria
authors.initials: A
authors.lastname: Morelli
authors.forename: Aravinda K
authors.initials: AK
authors.lastname: Chavalmane
authors.forename: Erica
authors.initials: E
authors.lastname: Sarchielli
authors.forename: Benedetta
authors.initials: B
authors.lastname: Fibbi
authors.forename: Farid
authors.initials: F
authors.lastname: Saad
authors.forename: Peter
authors.initials: P
authors.lastname: Sandner
authors.forename: Peggy
authors.initials: P
authors.lastname: Ruggiano
authors.forename: Gabriella B
authors.initials: GB
authors.lastname: Vannelli
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
mesh_terms: D000818:Animals; D001786:Blood Glucose; D004195:Disease Models, Animal; D004357:Drug Synergism; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology*; D005951:Glucose Tolerance Test; D007006:Hypogonadism / Q000150:complications / Q000188:drug therapy; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism*; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use*; D013739:Testosterone / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D013739:Testosterone; D000068677:Sildenafil Citrate