Beyond Hormone Transport: SHBG as a Modulator of Sex Hormone Delivery and Action

Our research centers on sex hormone–binding globulin (SHBG), a key circulating protein that regulates the bioavailability, distribution, and tissue access of sex hormones. Rather than acting as a passive carrier, SHBG critically controls when, where, and to what extent androgens and estrogens are delivered to target tissues or sequestered from excessive signaling.

Emerging evidence suggests that alterations in SHBG levels profoundly reshape sex hormone action in metabolic and inflammatory contexts. Clinically, low circulating SHBG is strongly associated with metabolic disorders such as type 2 diabetes and hormone-related cancers. Nutritional overload and chronic inflammation further suppress SHBG production, thereby enhancing free hormone exposure. However, whether changes in SHBG actively drive disease progression by dysregulating hormone delivery or merely reflect disease states remains unresolved.

A major obstacle in addressing this question has been the lack of appropriate experimental models, as standard laboratory mice do not express circulating SHBG after birth. To overcome this limitation, our group integrates patient samples with SHBG transgenic mouse models that recapitulate human-like hormone-binding dynamics. This approach allows us to directly test how SHBG-mediated modulation of sex hormone availability influences tissue-specific signaling.

Using this integrated strategy, we investigate how altered sex hormone delivery and restraint by SHBG contribute to the pathogenesis of chronic and inflammatory diseases, including diabetes, diabetic neuropathy, sarcopenia and cancers.

Ultimately, our goal is to redefine SHBG not simply as a static biomarker, but as an active regulator of sex hormone action and a potential therapeutic lever for restoring hormonal balance in chronic and age-related diseases.