Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells
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 acti...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2016/6437585 |
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| author | Huika Li Thy Pham Brett C. McWhinney Jacobus P. Ungerer Carel J. Pretorius Derek J. Richard Robin H. Mortimer Michael C. d’Emden Kerry Richard |
| author_facet | Huika Li Thy Pham Brett C. McWhinney Jacobus P. Ungerer Carel J. Pretorius Derek J. Richard Robin H. Mortimer Michael C. d’Emden Kerry Richard |
| author_sort | Huika Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c8bf8e00bb8a4be9ab992d0d6eb6db6f |
| institution | DOAJ |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-c8bf8e00bb8a4be9ab992d0d6eb6db6f2025-08-20T03:23:42ZengWileyInternational Journal of Endocrinology1687-83371687-83452016-01-01201610.1155/2016/64375856437585Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer CellsHuika Li0Thy Pham1Brett C. McWhinney2Jacobus P. Ungerer3Carel J. Pretorius4Derek J. Richard5Robin H. Mortimer6Michael C. d’Emden7Kerry Richard8Conjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, AustraliaSchool of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4000, AustraliaConjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, AustraliaConjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, AustraliaConjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, AustraliaSchool of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4000, AustraliaConjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, AustraliaConjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, AustraliaConjoint Endocrine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, AustraliaSex 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.http://dx.doi.org/10.1155/2016/6437585 |
| spellingShingle | Huika Li Thy Pham Brett C. McWhinney Jacobus P. Ungerer Carel J. Pretorius Derek J. Richard Robin H. Mortimer Michael C. d’Emden Kerry Richard Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells International Journal of Endocrinology |
| title | Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells |
| title_full | Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells |
| title_fullStr | Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells |
| title_full_unstemmed | Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells |
| title_short | Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells |
| title_sort | sex hormone binding globulin modifies testosterone action and metabolism in prostate cancer cells |
| url | http://dx.doi.org/10.1155/2016/6437585 |
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