+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Testosterone increases renal anti-aging klotho gene expression via the androgen receptor-mediated pathway

Testosterone increases renal anti-aging klotho gene expression via the androgen receptor-mediated pathway

Biochemical Journal 464(2): 221-229

Gender is known to be associated with longevity and oestrogen administration induced longevity-associated gene expression is one of the potential mechanisms underlying the benefits of oestrogen on lifespan, whereas the role of testosterone in the regulation of longevity-associated gene expressions remains largely unclear. The klotho gene, predominantly expressed in the kidney, has recently been discovered to be an aging suppressor gene. In the present study, we investigated the regulatory effects of testosterone on renal klotho gene expression in vivo and in vitro. In testosterone-administered mouse kidney and NRK-52E cells, increased klotho expression was accompanied by the up-regulation of the nuclear androgen receptor (AR). Overexpression of AR enhanced the expression of klotho mRNA and protein. Conversely, testosterone-induced klotho expression was attenuated in the presence of flutamide, an AR antagonist. A reporter assay and a chromatin immunoprecipitation (ChIP) assay demonstrated that AR directly binds to the klotho promoter via androgen response elements (AREs) which reconfirmed its importance for AR binding via the element mutation. In summary, our study demonstrates that testosterone up-regulates anti-aging klotho together with AR expression in the kidney in vivo and in vitro by recruiting AR on to the AREs of the klotho promoter.

(PDF emailed within 0-6 h: $19.90)

Accession: 056152763

Download citation: RISBibTeXText

PMID: 25163025

DOI: 10.1042/BJ20140739

Related references

Resveratrol increases anti-aging Klotho gene expression via the activating transcription factor 3/c-Jun complex-mediated signaling pathway. International Journal of Biochemistry and Cell Biology 53: 361-371, 2015

Vitamin D receptor controls expression of the anti-aging klotho gene in mouse and human renal cells. Biochemical and Biophysical Research Communications 414(3): 557-562, 2011

Examining a pathway for hormone mediated maternal effects--yolk testosterone affects androgen receptor expression and endogenous testosterone production in young chicks (Gallus gallus domesticus). General and Comparative Endocrinology 172(3): 487-493, 2011

Testosterone treatment increases androgen receptor and aromatase gene expression in myotubes from patients with PCOS and controls, but does not induce insulin resistance. Biochemical and Biophysical Research Communications 451(4): 622-626, 2014

The suppressive effects of testosterone on growth in young chickens appears to be mediated via a peripheral androgen receptor; studies of the anti-androgen ICI 176,334. Poultry Science 75(6): 763-766, 1996

Testosterone therapy delays cardiomyocyte aging via an androgen receptor-independent pathway. Brazilian Journal of Medical and Biological Research 44(11): 1118-1124, 2012

Physiological testosterone retards cardiomyocyte aging in Tfm mice via androgen receptor-independent pathway. Chinese Medical Sciences Journal 28(2): 88-94, 2013

Testosterone downregulates angiotensin II type-2 receptor via androgen receptor-mediated ERK1/2 MAP kinase pathway in rat aorta. Journal of the Renin-Angiotensin-Aldosterone System 17(4), 2016

Effects of intra- and extracellular factors on anti-aging klotho gene expression. Genetics and Molecular Research 10(3): 2009-2023, 2012

Deficiency in the anti-aging gene Klotho promotes aortic valve fibrosis through AMPKα-mediated activation of RUNX2. Aging Cell 15(5): 853-860, 2017

Statin upregulates the expression of klotho, an anti-aging gene, in experimental cyclosporine nephropathy. Nephron. Experimental Nephrology 120(4): E123-E133, 2015

Winning agonistic encounters increases testosterone and androgen receptor expression in Syrian hamsters. Hormones and Behavior 86: 27-35, 2016

Interleukin 6 activates androgen receptor-mediated gene expression through a signal transducer and activator of transcription 3-dependent pathway in LNCaP prostate cancer cells. Cancer Research 60(8): 2132-2135, 2000

Improvement of multiple pathophysiological phenotypes of klotho (kl/kl) mice by adenovirus-mediated expression of the klotho gene. Journal of Gene Medicine 2(4): 233-242, 2000

Androgen receptor‑mediated upregulation of quaking affects androgen receptor‑related prostate cancer development and anti‑androgen receptor therapy. Molecular Medicine Reports 17(6): 8203-8211, 2018