Effects of sex hormone-binding globulin (SHBG) on androgen bioactivity in vitro
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Usage of genetic SHBG variants in combination with the luciferase androgen reporter assay modifies in vitro androgen bioactivity and reveals increased activity for genetic variants that lower binding affinity.
“Indeed, usage of genetic SHBG variants in combination with the luciferase androgen reporter assay modifies in vitro androgen bioactivity and reveals increased activity for genetic variants that lower binding affinity [41].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [41]
Section 3.3 reports that the luciferase bioassay showed less suppression of androgen bioactivity with the binding-deficient S42L variant and the lower-affinity R123H variant than with wild-type SHBG. It found no detectable difference for two other variants with modestly lower binding affinity, R123C and P156L. The claim is therefore supported for some, but not all, lower-affinity variants tested. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAdding recombinant human SHBG to SHBG-deficient serum significantly reduces androgen bioactivity in vitro, confirming the inhibitory effect of SHBG on androgen exposure.
“Using this reporter assay, it was demonstrated that adding recombinant human SHBG to SHBG-deficient serum significantly reduces androgen bioactivity in vitro, hereby confirming the inhibitory effect of SHBG on androgen exposure [41].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [41]
Sex steroid-binding plasma proteins play a crucial role in the regulation of androgen action.
“These sex steroid-binding plasma proteins therefore play a crucial role in the regulation of androgen action (Laurent et al., 2016).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Laurent et al., 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 73 · Cited by 31
- Authors
- Laurent, M. R., Helsen, C., Antonio, L., Schollaert, D., Joniau, S., Vos, M. J., Decallonne, B., Hammond, G. L., Vanderschueren, D., & Claessens, F.
- Affiliations
- KU Leuven (BE)
- University Medical Center Groningen (NL)
- University of British Columbia (CA)
- Corresponding author
- Claessens, Frank
- ORCID
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 437
- Pages
- 280-291
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2510064153
- Cited by
- 31
- References
- 73
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 3
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Licence
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- FWO (G085413N)
- KU Leuven Research Council (GOA/15/017)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- sex hormone-binding globulin, androgen receptor, luciferase reporter assay, free testosterone, bioavailable testosterone, dilution effect, hypogonadism, testosterone replacement therapy, androgen receptor antagonists, androgen synthesis inhibitors, androgen deprivation therapy, prostate cancer, HEK293 cells
- MeSH terms
- Adult, Aged, Androgens, Animals, Biological Assay, Humans, Male, Mice, Transgenic, Middle Aged, Pilot Projects, Prostatic Neoplasms, Sex Hormone-Binding Globulin, Rats, Wistar, Serum, Mutant Proteins, Young Adult, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
