CoChat
Sign Up
Cited by 166Hormonal and reproductive studiesSexual function and dysfunction studiesHypothalamic control of reproductive hormones

Testosterone Partially Ameliorates Metabolic Profile and Erectile Responsiveness to PDE5 Inhibitors in an Animal Model of Male Metabolic Syndrome

Filippi, Sandra, Vignozzi, Linda, Morelli, Annamaria, Chavalmane, Aravinda K., Sarchielli, Erica, Fibbi, Benedetta, Saad, Farid, Sandner, Peter +4 more·2009·The Journal of Sexual Medicine
DOI 10.1111/j.1743-6109.2009.01467.x
Open this paper in CoChat — free account

Abstract

Introduction: 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). Aim: 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. Main Outcome Measures: 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. Conclusion: 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.

Integrity signals

Registry

Crossref · 10.1111/j.1743-6109.2009.01467.x

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Testosterone administration was able to restore sensitivity to acetylcholine and PDE5 inhibitors in MetS animals.

    “Interestingly, we previously reported that T administration was able to restore sensitivity to Ach and PDE5i [60].”

    From Treatment of Functional Hypogonadism Besides Pharmacological Substitution (2020) · cites this paper as [60]

  • The rabbit model of metabolic syndrome shares with the human phenotype several basic characteristics of MetS: hypertension, glucose intolerance, dyslipidemia, and increased visceral fat.

    “This animal model shares with the human phenotype several basic characteristics of MetS, i.e., hypertension, glucose intolerance, dyslipidemia, and increased visceral fat [60].”

    From Treatment of Functional Hypogonadism Besides Pharmacological Substitution (2020) · cites this paper as [60]

  • The rabbit model shows a MetS factor-dependent hypogonadotropic hypogonadism and erectile dysfunction.

    “In addition, these rabbits show a MetS factor-dependent hypogonadotropic HP and ED [60].”

    From Treatment of Functional Hypogonadism Besides Pharmacological Substitution (2020) · cites this paper as [60]

  • The distinction between a functional and an organic form of hypogonadism is captious because even diet-induced hypogonadotropic hypogonadism is associated with distinct organic alterations within the hypothalamus, the testis and the penis.

    “The distinction between a functional and an organic form of HG is, in some ways, captious because, as demonstrated in our preclinical model, even diet-induced hypogonadotropic HG is associated with distinct, organic alterations within the hypothalamus, the testis and the penis [606162].”

    From Treatment of Functional Hypogonadism Besides Pharmacological Substitution (2020) · cites this paper as [60]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Filippi, S., Vignozzi, L., Morelli, A., Chavalmane, A. K., Sarchielli, E., Fibbi, B., Saad, F., Sandner, P., Ruggiano, P., Vannelli, G. B., Mannucci, E., & Maggi, M.
Affiliations
  • University of Florence (IT)
  • Bayer (Germany) (DE)
Corresponding author
Maggi, Mario
ORCID
Venue
The Journal of Sexual Medicine
Publisher
Oxford University Press (OUP)
Published
2009-12-01
Volume
6
Issue
12
Pages
3274-3288
ISSN
  • 1743-6095 (ISSN-L)
  • 1743-6109
DOI
10.1111/j.1743-6109.2009.01467.x
OpenAlex
W2124892033
Cited by
166
References
57
Citations by year
2026: 4 · 2025: 6 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 8 · 2019: 9 · 2018: 9 · 2017: 8 · 2016: 5 · 2015: 9 · 2014: 20 · 2013: 19 · 2012: 16
FWCI
10.41
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • The Journal of Sexual Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Florence Research (University of Florence) (submittedVersion)
Funders
Ministero dell’Istruzione, dell’Università e della Ricerca
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
metabolic syndrome, testosterone supplementation, erectile dysfunction, hypogonadotropic hypogonadism, phosphodiesterase-5 inhibitors, high-fat diet, triptorelin, GnRH analogues, endothelial nitric oxide synthase, visceral obesity, animal models, rabbits
MeSH terms
Sildenafil Citrate, Animals, Blood Glucose, Disease Models, Animal, Drug Synergism, Glucose Tolerance Test, Hypogonadism, Erectile Dysfunction, Male, Phosphodiesterase Inhibitors, Piperazines, Purines, Rabbits, Sulfones, Testosterone, Metabolic Syndrome, Phosphodiesterase 5 Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review