Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Sex hormone binding globulin modifies testosterone action and metabolism in prostate cancer (LNCaP) cells (#357)

Huika Li 1 , Thy Pham 2 , Brett C McWhinney 1 , Jacobus P Ungerer 1 , Carel J Pretorius 1 , Derek J Richard 2 , Robin H Mortimer 1 , Michael C d'Emden 1 , Kerry Richard 1
  1. Queensland Health, Herston, QUEENSLAND, Australia
  2. Queensland University of Technology, Brisbane, Qld, Australia

The major role of Sex Hormone Binding Globulin (SHBG) is considered to be transport of steroid hormones in serum. However, growing evidence suggests that SHBG may play an intracellular role in regulating hormone action. Testosterone is thought to play an important role in prostate cancer cell growth and we have examined the effects of SHBG and testosterone on prostate cell growth and function. The androgen sensitive prostate cancer cell line, LNCaP, was exposed to various concentration of testosterone and SHBG both alone and in combination. The effects of SHBG on cell growth, testosterone uptake and metabolism and on testosterone induced gene expression were examined.

SHBG was internalised by LNCaP cells and uptake was not androgen dependent. In testosterone uptake assays, intracellular levels of testosterone peaked at 1 hour and thereafter increasing amounts of glucuronidated-testosterone was effluxed from the cell until almost 95% of testosterone was glucuronidated at 24 hours. In the presence of SHBG, only 7% of testosterone was glucuronidated at 24 hours suggesting that SHBG may have a protective effect. As expected, testosterone induced the expression of prostate specific antigen (PSA) mRNA. However addition of SHBG, rather than limiting testosterone function, further increased the testosterone-induced expression of PSA mRNA and further enhanced the testosterone-induced decrease in androgen receptor mRNA. The results strongly suggest that, as well as being the major serum carrier of sex hormones, SHBG is endocytosed and plays a role in the intracellular regulation of androgen action.