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Pioglitazone’s beneficial effects on erectile function preservation after cavernosal nerve injury in the rat are negated by inhibition of the insulin-like growth factor-1 receptor: a preclinical study

International Journal of Impotence Research volume 31, pages 1–8 (2019)Cite this article

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Abstract

To determine if the insulin-like growth factor-1 (IGF-1) pathway is involved in the improvement in erectile function recovery in rats after nerve crush injury treated with pioglitazone (Pio). Sprague-Dawley rats were divided into four groups. The first group received sham operation (n = 5). The second group underwent bilateral cavernous nerve injury (BCNI, n  = 7). The third group received BCNI and Pio treatment (BCNI  +  Pio, n = 7), whereas the fourth group underwent BCNI with Pio treatment and IGF-1 inhibition (BCNI  +  Pio  +  JB-1, n = 7). The IGF-1 receptor (IGF-1R) was inhibited by JB-1, a small molecular antagonist of the receptor. After 14 days of treatment, erectile function was measured via intracorporal pressure normalized to mean arterial pressure (ICP/MAP) and the major pelvic ganglion and cavernous nerve harvested for western blot and immunohistochemistry (IHC) of phosphorylated-IGF-1Rβ (p-IGF-1Rβ), phosphorylated-ERK1/2 (p-ERK1/2), and neuronal NOS (nNOS). BCNI  +  Pio animals exhibited improvements in ICP/MAP, similar to Sham animals, and BCNI  +  Pio  +  JB-1 rats demonstrated a reduced ICP/MAP similar to BCNI-only rats at all measured voltages. Western blot results showed upregulation of p-IGF-1Rβ was observed in the BCNI  +  Pio group. Low levels of p-ERK1/2 were seen in the JB-1-treated animals. The immunoblot results were supported by IHC findings. Intense IHC staining of nNOS was detected in the BCNI  +  Pio group. The group treated with JB-1 showed minimal protein expression of p-ERK1/2, nNOS, and p-IGF-1Rβ. Pio improves erectile function in rats undergoing BCNI via an IGF-1-mediated pathway.

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Funding

Funding for this project was provided by the Sexual Medicine Society of North America.

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Authors and Affiliations

  1. Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA

    Daniel J. Heidenberg, Nora M. Haney, Bashir M. Rezk, Sudha Talwar, Sudesh K. Srivastav, Matthew Honda, Salah Awadallah, James Anaissie, Taylor Peak, Kenneth J. DeLay, Phillip J. Kadowitz, Suresh C. Sikka, Asim B. Abdel Mageed & Wayne J. G. Hellstrom

  2. Department of Urology, George Washington School of Medicine and Health Sciences, Washington, DC, 20037, USA

    Daniel J. Heidenberg

  3. Department of Natural Sciences, Biology Unit, Southern University at New Orleans, New Orleans, LA, USA

    Bashir M. Rezk & Samuel C. Okpechi

  4. Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    Samuel C. Okpechi

  5. Louisiana State University Health Sciences Center, New Orleans, LA, USA

    Bryant Song & Kevin Swan

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Correspondence to Wayne J. G. Hellstrom.

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Heidenberg, D., Haney, N., Rezk, B.M. et al. Pioglitazone’s beneficial effects on erectile function preservation after cavernosal nerve injury in the rat are negated by inhibition of the insulin-like growth factor-1 receptor: a preclinical study. Int J Impot Res 31, 1–8 (2019). https://doi.org/10.1038/s41443-018-0054-2

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