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Cited by 43Prostate Cancer Treatment and ResearchHormonal and reproductive studiesSperm and Testicular Function

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

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Li, Huika, Pham, Thy, McWhinney, Brett C., Ungerer, Jacobus P., Pretorius, Carel J., Richard, Derek J., Mortimer, Robin H., d’Emden, Michael C. +1 more·2016·International Journal of Endocrinology
DOI 10.1155/2016/6437585PMC PMC5136390
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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.

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Cited by

Sorted by citations

Authors
Li, H., Pham, T., McWhinney, B. C., Ungerer, J. P., Pretorius, C. J., Richard, D. J., Mortimer, R. H., d’Emden, M. C., & Richard, K.
Affiliations
  • Queensland Health (AU)
  • Queensland University of Technology (AU)
  • Conjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, Australia
Corresponding author
Richard, Kerry
ORCID
Venue
International Journal of Endocrinology
Publisher
Wiley
Published
2016
Volume
2016
Pages
1-10
ISSN
  • 1687-8337 (ISSN-L)
  • 1687-8345
DOI
10.1155/2016/6437585
PMC
PMC5136390
OpenAlex
W2549886846
Cited by
43
References
2
Citations by year
2026: 2 · 2025: 2 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 5 · 2020: 1 · 2019: 4 · 2018: 5
FWCI
2.68
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Endocrinology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Royal Brisbane and Women’s Hospital Research Foundation
  • Science Education and Research Trust Fund
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
sex hormone-binding globulin, testosterone, prostate cancer, LNCaP cells, testosterone uptake, testosterone metabolism, testosterone glucuronide, androgen receptor, prostate-specific antigen, cell growth inhibition

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