کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8476694 | 1550842 | 2016 | 34 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effects of sex hormone-binding globulin (SHBG) on androgen bioactivity in vitro
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Effects of sex hormone-binding globulin (SHBG) on androgen bioactivity in vitro Effects of sex hormone-binding globulin (SHBG) on androgen bioactivity in vitro](/preview/png/8476694.png)
چکیده انگلیسی
Biochemical assessments of androgen status (hyper- or hypoandrogenism) are usually based on serum testosterone concentrations. According to the free hormone hypothesis, sex hormone-binding globulin (SHBG) determines free and bioavailable testosterone concentrations. Previous studies have suggested that in vitro androgen bioassay results may also be influenced by SHBG and correlate with free or bioavailable testosterone concentrations. To test this hypothesis, we established a stable HEK293 cell line with high expression of the human androgen receptor (AR) and a luciferase reporter downstream of a classical androgen response element. Importantly, we demonstrate that bioassay results are sensitive to dilution effects which increase apparent bioactivity in an SHBG-dependent manner. We therefore adopted a method using undiluted serum, which reduced cell proliferation but did not significantly affect the luciferase signal, cell viability or cytotoxicity. To correct for serum matrix effects, we applied signal correction based on internal controls with AR agonists or antagonists. Using this method, we provide direct evidence that in vitro androgen bioactivity reflects the inhibitory effects of SHBG, and correlates with free or bioavailable testosterone concentrations in adult hypogonadal men receiving androgen replacement therapy. In men receiving anti-androgens, serum bioactivity decreased tenfold while serum testosterone concentrations decreased only four-fold. Further pilot results in prostate cancer patients showed that androgen synthesis inhibitors result in more complete inhibition of androgen bioactivity than gonadorelin-based androgen deprivation therapy, even in patients whose testosterone concentrations were undetectable by mass spectrometry. We conclude that in vitro androgen reporter bioassays are useful tools to study how androgen bioactivity in serum is determined by androgens, anti-androgens as well as SHBG, provided that dilution and matrix effects are accounted for.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 437, 5 December 2016, Pages 280-291
Journal: Molecular and Cellular Endocrinology - Volume 437, 5 December 2016, Pages 280-291
نویسندگان
Michaël R. Laurent, Christine Helsen, Leen Antonio, Dieter Schollaert, Steven Joniau, Michel J. Vos, Brigitte Decallonne, Geoffrey L. Hammond, Dirk Vanderschueren, Frank Claessens,