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).
To clarify the relationships among MetS, hypogonadism, and ED, we developed an animal
model of MetS.
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.
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.
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.
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.