New Mechanism Discovered: How Chemicals Disrupt Sex Hormones

Researchers at the University of Oulu have identified a previously unknown mechanism in humans that may explain why certain medicines and environmental chemicals disrupt the balance of sex hormones. This significant discovery deepens the scientific understanding of endocrine disruptors — chemicals known to interfere with the body's hormonal systems.

The Role of PXR and SHBG

The core of this research centers on the pregnane X receptor (PXR), a protein known for monitoring the body's chemical burden. While PXR is primarily recognized for its role in regulating how the liver processes medicines, the new findings indicate it also profoundly influences the production of Sex Hormone-Binding Globulin (SHBG).

SHBG is a crucial protein that transports sex hormones, such as testosterone and estrogen, in the bloodstream. By doing so, SHBG helps regulate their overall levels and determines their availability for the body's use.

Key Findings from the Rifampicin Study

To investigate this connection, healthy volunteers in the study received the antibiotic rifampicin, a potent PXR activator, for one week. The results were striking:

• SHBG levels in the blood doubled in almost all participants.
• In men, total testosterone levels also increased significantly.

Further experiments conducted in liver cells corroborated these findings, demonstrating that rifampicin directly boosted SHBG production. Crucially, this effect was entirely eliminated when PXR was blocked, confirming PXR's direct involvement.

"A new PXR–SHBG–testosterone pathway has been identified that explains how chemical substances can disturb the balance of sex hormones in humans."
— Professor Janne Hukkanen, Lead Researcher

Implications for Everyday Chemicals

According to the researchers, these findings strongly suggest that many common chemicals may indirectly influence sex hormones by increasing SHBG production through PXR activation.

PXR can be activated by a wide array of substances, including certain medicines, compounds found in food, and environmental chemicals. This includes common exposures such as pesticides, flame retardants, and plastic additives. Consequently, the researchers believe this finding may have broad significance across various fields.

Advancing Endocrine Disruptor Research

Professor of Internal Medicine Janne Hukkanen, who led the study, emphasized the practical impact of their work.

Understanding this newly identified PXR–SHBG–testosterone mechanism improves the ability to predict how different medicines and environmental chemical exposures may affect hormonal systems. This knowledge is vital for developing safer substances and effectively reducing their harmful effects on human health.