Abstract
The aim of this study was to investigate the involvement of androgen, mainly testosterone, in the expression of renal senescence marker protein-30 (SMP30) in male rats. We found that the renal SMP30 expression was up-regulated by endogenous testosterone stimulation during puberty. Interestingly, androgen-deficient orchidectomized (ORX) rats exhibited lower SMP30 mRNA and protein expression in the kidney, and that was restored by testosterone propionate (TP) replacement. Abrogation of androgen receptor (AR) activity by co-treatment with flutamide abolished testosterone-induced SMP30 expression in the kidney as well as in the NRK52E cells. However, SMP30 expression was unaltered in the liver of ORX rats. We also showed a positive correlation between renal SMP30 expression and plasma testosterone level during the aging process. TP-induced SMP30 expression in ovariectomized (OVX) rats was observed and was an evidence to explain the gender difference of SMP30 levels. Immunofluorescence assay showed that renal SMP30 was specifically expressed in the proximal tubular segments of the kidney. The urinary Ca2+ level was increased in both ORX and male aging rats. Taken together, our results indicate a novel role of testosterone in regulating SMP30 expression specifically in the kidney to contribute to urinary calcium absorption.
Highlights
Aging is characterized by environmental or physiological pressures to trigger cellular senescence and disturb body homeostatic mechanism, leading to a progressive functional loss of physiological integrity[1]
We found that the puberty-associated enhancement of plasma testosterone was observed in young (2–3 months old) rats (Fig. 1A)
There was no difference in the plasma Ca2+ level, volume of urine, water intake and plasma parathyroid hormone (PTH) among all the four groups (Supplementary Table S2). These results suggested that testosterone enhanced renal Senescence marker protein-30 (SMP30) expression participates in the regulation of urinary calcium and might be involved in the maintenance of Ca2+ homeostasis
Summary
Aging is characterized by environmental or physiological pressures to trigger cellular senescence and disturb body homeostatic mechanism, leading to a progressive functional loss of physiological integrity[1]. Longitudinal studies have suggested that rapid bone loss after 65 year of age in men, which is related to deficient levels of testosterone or estradiol[3]. An epidemiologic study has indicated that elderly men with high urinary calcium excretion are associated with higher frequency of reduction in bone mineral density (BMD)[5]. We investigated the effect of testosterone on SMP30 expression in rat kidney. Our results demonstrated that testosterone has a role in stimulating SMP30 mRNA and protein expression through androgen receptor (AR) in rat kidney, which contributes to regulate urinary Ca2+ concentration. These findings present a novel role of testosterone in the regulation of SMP30 expression
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