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

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.

Induction of renal senescence marker protein-30 (SMP30) expression by testosterone and its contribution to urinary calcium absorption in male rats

“…Total RNAs were isolated from rat kidney and liver tissues with Trizol reagent (Invitrogen-Life Technologies, Grand Island, NY, USA) as described 37 . Two micrograms of total RNA was reverse transcribed to synthesize cDNA using ThermoScript™ RT-PCR System (Life technologies, Grand Island, NY, USA) for RT-PCR.…”

Determination of M1/M2 Macrophage Polarization in Ipsilateral and Contralateral Rat Testis Tissue Following Unilateral Torsion/Detorsion

“…Cho et al (2010) reported a decrease in plasma LH concentrations in both the sham and torsion groups in their study, and suggested that the reduction in this hormone could be associated with the effect of stress on the hypothalamus-pituitary–gonadal axis. The same study reported serum testosterone levels to be decreased as a result of the reduction of LH, while an evaluation of FSH levels – an indicator of spermatogenesis – revealed a minimal decrease in the torsion groups [ 31 ]. In the present study, decreases in serum FSH, LH and testosterone levels were detected in the torsion groups when compared with the control group, which supports the previous findings in literature.…”

The role of serum-glucocorticoid regulated kinase 1 in reproductive viability: implications from prenatal programming and senescence

“…Other studies have shown that SGK1 promotes the proliferation and anti-apoptosis of immature SCs [ 58 ] through PI3K, PDK1, AKT signaling pathways [ 59 , 60 ], regulates the protein synthesis and cytoskeleton of mature SCs to change the structure of BTB [ 60 ], and promotes spermatogenesis. In addition, SGK1 highlights the role of FoxO3a in regulating oxidative stress [ 61 ], which can damage BTB by destroying BTB-associated junction proteins and inducing apoptosis of Sertoli cells, leading to testicular damage and spermatogenesis disorders [ 62 ], which could lead to male infertility [ 63 ].…”