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Testosterone regulates the autophagic clearance of androgen binding protein in rat Sertoli cells.

Ma Y, Yang HZ, Xu LM, Huang YR, Dai HL, Kang XN - Sci Rep (2015)

Bottom Line: Dysregulation of androgen-binding protein (ABP) is associated with a number of endocrine and andrology diseases.Further studies identified that the autophagic clearance of ABP might be selectively regulated by testosterone, independent of stress (hypoxia)-induced autophagic degradation.These data demonstrate that testosterone up-regulates ABP expression at least partially by suppressing the autophagic degradation.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Biobank, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Building 1, 1630 DongFang Road, Shanghai. 200127, China [2] Department of Urology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Building 7, 1630 DongFang Road, Shanghai. 200127, China.

ABSTRACT
Dysregulation of androgen-binding protein (ABP) is associated with a number of endocrine and andrology diseases. However, the ABP metabolism in Sertoli cells is largely unknown. We report that autophagy degrades ABP in rat Sertoli cells, and the autophagic clearance of ABP is regulated by testosterone, which prolongs the ABP biological half-life by inhibiting autophagy. Further studies identified that the autophagic clearance of ABP might be selectively regulated by testosterone, independent of stress (hypoxia)-induced autophagic degradation. These data demonstrate that testosterone up-regulates ABP expression at least partially by suppressing the autophagic degradation. We report a novel finding with respect to the mechanisms by which ABP is cleared, and by which the process is regulated in Sertoli cells.

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Related in: MedlinePlus

ABP colocalises with LC3 in primary Sertoli cells.(A), Rat primary Sertoli cells were treated with CQ (50 uM) or rapamycin (10 nM) for 24 h (n = 3), or treated with ATG7 or MTOR siRNA for 48 h (n = 3), ABP mRNA was determined by qPCR. (B–C), Cells were treated with CQ or rapamycin for 24 h, and ABP and LC3 were assessed with double immunofluorescence (B). The average number of colocalisations per cell was calculated from 10 random fields (approximately 200 cells) (C) (n = 3, **p < 0.01).
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f2: ABP colocalises with LC3 in primary Sertoli cells.(A), Rat primary Sertoli cells were treated with CQ (50 uM) or rapamycin (10 nM) for 24 h (n = 3), or treated with ATG7 or MTOR siRNA for 48 h (n = 3), ABP mRNA was determined by qPCR. (B–C), Cells were treated with CQ or rapamycin for 24 h, and ABP and LC3 were assessed with double immunofluorescence (B). The average number of colocalisations per cell was calculated from 10 random fields (approximately 200 cells) (C) (n = 3, **p < 0.01).

Mentions: To investigate how autophagy regulates ABP expression, we first detected ABP gene transcription, and found that either inhibition or stimulation of autophagy did not change the ABP mRNA levels (Fig. 2A). We then used anti-ABP and anti-LC3 antibodies to identify their positions, and the results revealed that ABP colocalised with LC3 in primary rat Sertoli cells (Fig. 2B), indicating that ABP is engulfed by the autophagosomes and, therefore, degraded by lysosomes. We also found their colocalisation was promoted by either CQ or rapamycin treatment (Fig. 2B, 2C), suggesting that the ABP expression level is regulated by the autophagic flux.


Testosterone regulates the autophagic clearance of androgen binding protein in rat Sertoli cells.

Ma Y, Yang HZ, Xu LM, Huang YR, Dai HL, Kang XN - Sci Rep (2015)

ABP colocalises with LC3 in primary Sertoli cells.(A), Rat primary Sertoli cells were treated with CQ (50 uM) or rapamycin (10 nM) for 24 h (n = 3), or treated with ATG7 or MTOR siRNA for 48 h (n = 3), ABP mRNA was determined by qPCR. (B–C), Cells were treated with CQ or rapamycin for 24 h, and ABP and LC3 were assessed with double immunofluorescence (B). The average number of colocalisations per cell was calculated from 10 random fields (approximately 200 cells) (C) (n = 3, **p < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352847&req=5

f2: ABP colocalises with LC3 in primary Sertoli cells.(A), Rat primary Sertoli cells were treated with CQ (50 uM) or rapamycin (10 nM) for 24 h (n = 3), or treated with ATG7 or MTOR siRNA for 48 h (n = 3), ABP mRNA was determined by qPCR. (B–C), Cells were treated with CQ or rapamycin for 24 h, and ABP and LC3 were assessed with double immunofluorescence (B). The average number of colocalisations per cell was calculated from 10 random fields (approximately 200 cells) (C) (n = 3, **p < 0.01).
Mentions: To investigate how autophagy regulates ABP expression, we first detected ABP gene transcription, and found that either inhibition or stimulation of autophagy did not change the ABP mRNA levels (Fig. 2A). We then used anti-ABP and anti-LC3 antibodies to identify their positions, and the results revealed that ABP colocalised with LC3 in primary rat Sertoli cells (Fig. 2B), indicating that ABP is engulfed by the autophagosomes and, therefore, degraded by lysosomes. We also found their colocalisation was promoted by either CQ or rapamycin treatment (Fig. 2B, 2C), suggesting that the ABP expression level is regulated by the autophagic flux.

Bottom Line: Dysregulation of androgen-binding protein (ABP) is associated with a number of endocrine and andrology diseases.Further studies identified that the autophagic clearance of ABP might be selectively regulated by testosterone, independent of stress (hypoxia)-induced autophagic degradation.These data demonstrate that testosterone up-regulates ABP expression at least partially by suppressing the autophagic degradation.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Biobank, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Building 1, 1630 DongFang Road, Shanghai. 200127, China [2] Department of Urology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Building 7, 1630 DongFang Road, Shanghai. 200127, China.

ABSTRACT
Dysregulation of androgen-binding protein (ABP) is associated with a number of endocrine and andrology diseases. However, the ABP metabolism in Sertoli cells is largely unknown. We report that autophagy degrades ABP in rat Sertoli cells, and the autophagic clearance of ABP is regulated by testosterone, which prolongs the ABP biological half-life by inhibiting autophagy. Further studies identified that the autophagic clearance of ABP might be selectively regulated by testosterone, independent of stress (hypoxia)-induced autophagic degradation. These data demonstrate that testosterone up-regulates ABP expression at least partially by suppressing the autophagic degradation. We report a novel finding with respect to the mechanisms by which ABP is cleared, and by which the process is regulated in Sertoli cells.

Show MeSH
Related in: MedlinePlus