Researchers at the University of Oulu announced on Mar. 11 that they have discovered a previously unknown mechanism in humans that may explain how certain medicines and environmental chemicals disrupt the balance of sex hormones. The study focuses on the pregnane X receptor (PXR), which is known for regulating how the liver processes medicines, but has now been shown to also influence the production of SHBG, a protein responsible for transporting sex hormones in the bloodstream.
This discovery is significant because it deepens scientific understanding of endocrine disruptors—chemicals that interfere with hormonal systems. SHBG plays a key role in regulating levels of hormones such as testosterone and oestrogen, determining how much is available for use by the body.
In their research, healthy volunteers were given rifampicin, an antibiotic recognized as one of the strongest activators of PXR, for one week. The results showed that SHBG levels in participants' blood doubled in almost all cases, and total testosterone levels rose in men. Further experiments using liver cells demonstrated that rifampicin increased SHBG production; however, this effect disappeared when PXR was blocked.
The researchers say these findings suggest many everyday chemicals could influence sex hormone levels indirectly by increasing SHBG production through PXR activation. "We have long known that some chemical substances can disturb the balance of sex hormones. Now we’ve identified a mechanism - a new PXR–SHBG–testosterone pathway - that explains these effects in humans," said Professor of Internal Medicine Janne Hukkanen, who led the study at the University of Oulu.
PXR can be activated by various chemicals including certain medicines, food compounds, and environmental chemicals such as pesticides, flame retardants, and plastic additives. The team believes this finding may have broad implications for understanding how exposure to different substances affects human health.
The study was published in Basic & Clinical Pharmacology & Toxicology.
