Role of serum- and glucocorticoid-inducible kinase-1 in regulating torsion-induced apoptosis in rats

Y.-M Cho,S.-W Wang,H.-F Pu,W J Huang,L.-T Ho,P S Wang

doi:10.1111/j.1365-2605.2010.01091.x

Abstract

Serum- and glucocorticoid-inducible kinase-1 (SGK1) is a serine/threonine protein kinase that responds to various stimuli and mediates cell survival. Although it is known that testicular torsion leads to testicular damage and male infertility, the role of SGK1 in torsion remains unclear. This study investigated whether torsion-induced apoptosis is associated with changes in phosphoinositide-dependent protein kinase-1 (PDK1), SGK1 and forkhead transcription factor FOXO3a expression and/or phosphorylation in rats. Sprague-Dawley rats were divided into four groups: sham (control), 1, 2 and 4 h of unilateral torsion. Bilateral testes, testicular interstitial fluid (TIF) and blood samples were collected immediately after torsion. Our results revealed that SGK1 protein and mRNA were abundantly present in testes and were induced by 2 h of torsion, but that phosphorylation of SGK1, PDK1 and FOXO3a decreased simultaneously. After 2 h of torsion, the testosterone secretion capacity of the primary Leydig cells and testicular interstitial cells (TICs) was impaired and apoptotic spermatogonia and TICs were observed; in addition, the mean seminiferous tubular diameter was decreased. Torsion increased plasma corticosterone levels, but decreased plasma luteinizing hormone and testosterone levels. However, the testosterone levels of the TIF in the ipsilateral testes were significantly enhanced after 2 h of torsion, but suppressed in the contralateral testes. This animal study suggests that PDK1, SGK1 and FOXO3a are involved in torsion-induced apoptosis and that medical therapy should be performed as early as 2 h after the occurrence of torsion to prevent further damage.

Highlights

Testicular torsion leads to infertility (Filho et al, 2004); it is caused by spermatic cord twisting (Turner & Brown, 1993; Turner et al, 2005)
Expression of FOXO3a (Fig. 6J) cannot be directly correlated with cells undergo-. The results from this in vivo study support our hypothesis that testicular ischaemia-induced apoptosis is associated with the PDK1, Serum- and glucocorticoid-inducible kinase-1 (SGK1) and FOXO3a signalling cascade
After torsion stimulation, that the PDK1 ⁄ SGK1 ⁄ FOXO3a signalling cascade was downregulated, that the plasma corticosteroid level was increased, that plasma luteinizing hormone (LH) and testosterone levels were decreased and that the testosterone-secreting capacity of Leydig cells (LCs) and testicular interstitial cells (TICs) was impaired

Summary

Introduction

Testicular torsion leads to infertility (Filho et al, 2004); it is caused by spermatic cord twisting (Turner & Brown, 1993; Turner et al, 2005). This obstruction of blood supply to the testes creates a condition in which there is a shortage of oxygen and nutrients from the blood and this results in testicular cell damage. Previous evidence from various ischaemia ⁄ reperfusion models has indicated that both necrosis and apoptosis are mechanisms for ischaemia- ⁄ reperfusion-induced cell death (Shiraishi et al, 2000, 2001). The detailed apoptotic mechanisms induced by up to 4 h testicular torsion remain to be determined

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Discussion

Conclusion