ArticleBasic & clinical pharmacology & toxicology2026
Pregnane X Receptor Regulates Human Endocrine System by Inducing Sex Hormone-Binding Globulin Expression.
Article in Basic & clinical pharmacology & toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Sex hormone-binding globulin (SHBG) is a sex hormone carrier. We aimed to characterize the role of pregnane X receptor (PXR), a major regulator of drug metabolism, in SHBG regulation. Serum SHBG was measured in four clinical trials (n = 61) and expression in in vitro experiments in human 3D hepatocyte spheroids and HepG2 cells. We also analysed previously published chromatin immunoprecipitation sequencing data from cryopreserved human hepatocytes. One-week dosing of PXR ligand rifampicin increased SHBG in all but one healthy volunteer (geometric mean induction 2.0-fold; SHBG concentration 70.5 ± 34.1 nmol/L with rifampicin and 36.1 ± 19.0 nmol/L with control; p < 0.0001; 95% confidence interval of the mean of differences between arms 31.9-42.0). In men, serum total testosterone increased and free androgen index decreased. In 3D human hepatocyte spheroids, rifampicin caused a clear induction of SHBG mRNA, while SPA70, a PXR antagonist, decreased both basal and rifampicin-induced SHBG mRNA expression. Analysis of ChIP-sequencing data identified a rifampicin-induced PXR binding site within the SHBG gene. These results show that PXR is a novel regulator of serum SHBG in humans. This mechanism may mediate effects of PXR-activating drugs and other chemicals on sex hormone balance and have implications for metabolic health.
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