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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/28320
Title: Regulatory role of testosterone in organic cation transport: In vivo and in vitro studies
Authors: Paranee Meetam
Chutima Srimaroeng
Sunhapas Soodvilai
Varanuj Chatsudthipong
Mahidol University
National Institute of Environmental Health Sciences
Keywords: Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jun-2009
Citation: Biological and Pharmaceutical Bulletin. Vol.32, No.6 (2009), 982-987
Abstract: The renal proximal tubule (RPT) plays a crucial role in organic cation (OC) secretion and has a major impact on pharmacokinetics of OC drugs. Secretory transport is vectorial. Thus, it involves transporters located at both basolateral and apical membranes. Although sex hormones have been shown to regulate OC transport, there is little data on the effect of testosterone on OC secretion in a whole animal. Therefore, we determined the clearance of tetraethylammonium (TEA), a model OC substrate, in intact and castrated male mice. Castration significantly decreased renal TEA secretion by 30%, and testosterone supplementation returned TEA secretion to control levels in castrated mice. The mechanism of this effect was further examined in isolated mouse renal proximal tubules (mRPT). TEA uptake in isolated mRPT from castrated mice was reduced by 36%. This effect was reversed in tubules from castrated mice supplemented with testosterone. Kinetic analysis of [3H]-TEA uptake in isolated mRPT showed a decreased Vmax with no change in K m, implying that the decrease in transport rate was caused by lowering in the number of transporters in castrated mice rather than a change in transporter affinity. Quantitative real time polymerase chain reaction (real time PCR) revealed that organic cation transporter (OCT)2 is the major TEA transporter in male mice. Moreover, OCT2 mRNA level was significantly reduced after castration. Castrated mice also showed a modest increase in organic cation/carnitine transporter 1 (OCTN1) mRNA level, indicating that testosterone may also regulate apical OCTN1 expression. These data suggest that testosterone regulates transepithelial transport of OC through modulation of OCT2 expression in male mice. © 2009 Pharmaceutical Society of Japan.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=66549096122&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/28320
ISSN: 13475215
09186158
Appears in Collections:Scopus 2006-2010

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