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Article Open Access

Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway

  • Authors:
    • Jing Zhao
    • Ge‑Li Liu
    • Ying Wei
    • Li‑Hong Jiang
    • Peng‑Li Bao
    • Qing‑Yan Yang
  • View Affiliations / Copyright

    Affiliations: Department of Paediatrics, General Hospital of Tianjin Medical University, Tianjin 300052, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2518-2526
    |
    Published online on: July 27, 2016
       https://doi.org/10.3892/mmr.2016.5562
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Abstract

The aim of the present study was to investigate the effect of testosterone on glucolipid metabolism and vascular injury in male rats, and examine the underlying molecular mechanisms. A total of 40 male Sprague-Dawley rats were divided into a control group (n=10), high-fat-diet + castration group (n=10), high‑fat‑diet + castration + low dose testosterone group (n=10), and high-fat-diet + castration + high dose testosterone group (n=10). Hematoxylin and eosin staining was performed to evaluate the morphology of the thoracic aortic tissues. Immunohistochemical staining was used to detect biomarkers of the phosphoinositide 3‑kinase (PI3K) signaling pathway. The mRNA and protein expression levels of PI3K, AKT, insulin receptor substrate‑1 (IRS‑1), glucose transporter type 4 (GLUT‑4), nuclear factor (NF)‑κB and tumor necrosis factor (TNF)‑α in the aortas were determined using quantitative polymerase chain reaction and Western blot analyses, respectively. Apoptosis in the aortic tissues was detected using a TUNEL assay. Castration induced apoptosis in the animals fed a high‑fat‑diet, whereas low dose testosterone replacement ameliorated the apoptosis in the aorta. However, the levels of apoptosis was more severe following high‑dose testosterone treatment. Low‑dose testosterone induced upregulation in the levels of IRS‑1, AKT, GLUT‑4 protein, NF‑κB, TNF‑α and PI3K, compared with those in the animals fed a high‑fat diet following castration. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT, GLUT‑4, NF‑κB, TNF‑α and PI3K. Compared with the rats in the high‑fat diet + castration group, a low dose of testosterone induced upregulation in the mRNA levels of IRS‑1, AKT and GLUT‑4, and downregulation of the mRNA levels of NF‑κB, TNF‑α and PI3K. A high dose of testosterone resulted in a significant decrease in the levels of IRS‑1, AKT and GLUT‑4, and marked increases in the mRNA levels of NF‑κB, TNF‑α and PI3K, compared with the low dose group. Castration induced marked disorders of glucolipid metabolism and vascular injuries in the pubescent male rats. Low‑dose testosterone treatment was found to ameliorate the vascular damage caused by castration via the PI3K/AKT signaling pathway.
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1 

Karoutsou E and Polymeris A: Environmental endocrine disruptors and obesity. Endocr Regul. 46:37–46. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Boodai SA, Cherry LM, Sattar NA and Reilly JJ: Prevalence of cardiometabolic risk factors and metabolic syndrome in obese Kuwaiti adolescents. Diabetes Metab Syndr Obes. 7:505–511. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Kursawe R and Santoro N: Metabolic syndrome in pediatrics. Adv Clin Chem. 65:91–142. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Özer S, Yılmaz R, Özlem Kazancı N, Sönmezgöz E, Karaaslan E, Altuntaş B and Emre Kuyucu Y: Higher HDL levels are a preventive factor for metabolic syndrome in obese Turkish children. Nutr Hosp. 31:307–312. 2014.

5 

Denzer C, Thiere D, Muche R, Koenig W, Mayer H, Kratzer W and Wabitsch M: Gender-specific prevalences of fatty liver in obese children and adolescents: Roles of body fat distribution, sex steroids and insulin resistance. J Clin Endocrinol Metab. 94:3872–3881. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Shelton JB and Rajfer J: Androgen deficiency in aging and metabolically challenged men. Urol Clin North Am. 39:63–75. 2012. View Article : Google Scholar

7 

Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A and Dandona P: Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab. 89:5462–5468. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Moriarty-Kelsey M, Harwood JE, Travers SH, Zeitler PS and Nadeau KJ: Testosterone, obesity and insulin resistance in young males: Evidence for an association between gonadal dysfunction and insulin resistance during puberty. J Pediatr Endocrinol Metab. 23:1281–1287. 2010. View Article : Google Scholar

9 

Janjgava S, Zerekidze T, Uchava L, Giorgadze E and Asatiani K: Influence of testosterone replacement therapy on metabolic disorders in male patients with type 2 diabetes mellitus and androgen deficiency. Eur J Med Res. 19:562014. View Article : Google Scholar : PubMed/NCBI

10 

Sattler F, He J, Chukwuneke J, Kim H, Stewart Y, Colletti P, Yarasheski K and Buchanan T: Testosterone supplementation improves carbohydrate and lipid metabolism in some older men with abdominal obesity. J Gerontol Geriatr Res. 3:10001592014.PubMed/NCBI

11 

Yeap BB, Alfonso H, Chubb SA, Handelsman DJ, Hankey GJ, Golledge J, Flicker L and Norman PE: Lower plasma testosterone or dihydrotestosterone, but not estradiol, is associated with symptoms of intermittent claudication in older men. Clin Endocrinol (Oxf). 79:725–732. 2013.

12 

Srinath R, Hill Golden S, Carson KA and Dobs A: Endogenous testosterone and its relationship to preclinical and clinical measures of cardiovascular disease in the atherosclerosis risk in communities (ARIC) study. J Clin Endocrinol Metab. 100:1602–1608. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Yu J, Akishita M, Eto M, Ogawa S, Son BK, Kato S, Ouchi Y and Okabe T: Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells: Role of phosphatidylinositol 3-kinase/akt pathway. Endocrinology. 151:1822–1828. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Li F, Li L, Zhong Y, Xie Q, Huang J, Kang X, Wang D, Xu L and Huang T: Relationship between LTR methylation and gag expression of HIV-1 in human spermatozoa and sperm-derived embryos. PLoS One. 8:e548012013. View Article : Google Scholar : PubMed/NCBI

15 

Beaudin G: Men and low testosterone. Diabetes Self Manag. 32:24–27. 2015.PubMed/NCBI

16 

Jockenhövel F: Testosterone therapy - what, when and to whom? Aging Male. 7:319–324. 2004. View Article : Google Scholar

17 

Botella-Carretero JI, Balsa JA, Gómez-Martin JM, Peromingo R, Huerta L, Carrasco M, Arrieta F, Zamarron I, Martin-Hidalgo A and Vazquez C: Circulating free testosterone in obese men after bariatric surgery increases in parallel with insulin sensitivity. J Endocrinol Invest. 36:227–232. 2013.

18 

Zhang N, Zhang H, Zhang X, Zhang B, Wang F, Wang C, Zhao M, Yu C, Gao L, Zhao J and Guan Q: The relationship between endogenous testosterone and lipid profile in middle-aged and elderly Chinese men. Eur J Endocrinol. 170:487–494. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Gu YQ, Wang XH, Xu D, Peng L, Cheng LF, Huang MK, Huang ZJ and Zhang Y: A multicenter contraceptive efficacy study of injectable testosterone undecanoate in healthy Chinese men. J Clin Endocrinol Metab. 88:562–568. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Gårevik N, Rane A, Björkhem-Bergman L and Ekström L: Effects of different doses of testosterone on gonadotropins, 25-hydroxyvitamin D3 and blood lipids in healthy men. Subst Abuse Rehabil. 5:121–127. 2014. View Article : Google Scholar

21 

Rosano GM, Sheiban I, Massaro R, Pagnotta P, Marazzi G, Vitale C, Mercuro G, Volterrani M, Aversa A and Fini M: Low testosterone levels are associated with coronary artery disease in male patients with angina. Int J Impot Res. 19:176–182. 2007. View Article : Google Scholar

22 

Shores MM, Matsumoto AM, Sloan KL and Kivlahan DR: Low serum testosterone and mortality in male veterans. Arch Intern Med. 166:1660–1665. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Duckles SP and Miller VM: Hormonal modulation of endothelial NO production. Pflugers Arch. 459:841–851. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Lapauw B, Ouwens M, 't Hart LM, Wuyts B, Holst JJ, T'Sjoen G, Kaufman JM and Ruige JB: Sex steroids affect triglyceride handling, glucose-dependent insulinotropic polypeptide and insulin sensitivity: A 1-week randomized clinical trial in healthy young men. Diabetes Care. 33:1831–1833. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ and McKinlay JB: Low sex hormone-binding globulin, total testosterone and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab. 91:843–850. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, Morales AM, Volterrani M, Yellowlees A, Howell JD and Channer KS; TIMES2 Investigators: Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 34:828–837. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Guay AT: The emerging link between hypogonadism and metabolic syndrome. J Androl. 30:370–376. 2009. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Zhao J, Liu GL, Wei Y, Jiang LH, Bao PL and Yang QY: Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway. Mol Med Rep 14: 2518-2526, 2016.
APA
Zhao, J., Liu, G., Wei, Y., Jiang, L., Bao, P., & Yang, Q. (2016). Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway. Molecular Medicine Reports, 14, 2518-2526. https://doi.org/10.3892/mmr.2016.5562
MLA
Zhao, J., Liu, G., Wei, Y., Jiang, L., Bao, P., Yang, Q."Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway". Molecular Medicine Reports 14.3 (2016): 2518-2526.
Chicago
Zhao, J., Liu, G., Wei, Y., Jiang, L., Bao, P., Yang, Q."Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway". Molecular Medicine Reports 14, no. 3 (2016): 2518-2526. https://doi.org/10.3892/mmr.2016.5562
Copy and paste a formatted citation
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Spandidos Publications style
Zhao J, Liu GL, Wei Y, Jiang LH, Bao PL and Yang QY: Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway. Mol Med Rep 14: 2518-2526, 2016.
APA
Zhao, J., Liu, G., Wei, Y., Jiang, L., Bao, P., & Yang, Q. (2016). Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway. Molecular Medicine Reports, 14, 2518-2526. https://doi.org/10.3892/mmr.2016.5562
MLA
Zhao, J., Liu, G., Wei, Y., Jiang, L., Bao, P., Yang, Q."Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway". Molecular Medicine Reports 14.3 (2016): 2518-2526.
Chicago
Zhao, J., Liu, G., Wei, Y., Jiang, L., Bao, P., Yang, Q."Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway". Molecular Medicine Reports 14, no. 3 (2016): 2518-2526. https://doi.org/10.3892/mmr.2016.5562
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