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International Journal of Endocrinology
Volume 2016, Article ID 6437585, 10 pages
http://dx.doi.org/10.1155/2016/6437585
Research Article

Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells

1Conjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, Australia
2School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4000, Australia
3Department of Endocrinology and Diabetes, Royal Brisbane and Women’s Hospital, Herston, QLD 4029, Australia

Received 15 June 2016; Revised 10 October 2016; Accepted 20 October 2016

Academic Editor: Sergio D. Paredes

Copyright © 2016 Huika Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Sex Hormone Binding Globulin (SHBG) is the major serum carrier of sex hormones. However, growing evidence suggests that SHBG is internalised and plays a role in regulating intracellular hormone action. This study was to determine whether SHBG plays a role in testosterone uptake, metabolism, and action in the androgen sensitive LNCaP prostate cancer cell line. Internalisation of SHBG and testosterone, the effects of SHBG on testosterone uptake, metabolism, regulation of androgen responsive genes, and cell growth were assessed. LNCaP cells internalised SHBG by a testosterone independent process. Testosterone was rapidly taken up and effluxed as testosterone-glucuronide; however this effect was reduced by the presence of SHBG. Addition of SHBG, rather than reducing testosterone bioavailability, further increased testosterone-induced expression of prostate specific antigen and enhanced testosterone-induced reduction of androgen receptor mRNA expression. Following 38 hours of testosterone treatment cell morphology changed and growth declined; however, cotreatment with SHBG abrogated these inhibitory effects. These findings clearly demonstrate that internalised SHBG plays an important regulatory and intracellular role in modifying testosterone action and this has important implications for the role of SHBG in health and disease.