Inflammatory Correlates SHBG refers to the well-documented clinical relationship where chronic, low-grade systemic inflammation significantly and dynamically influences the circulating concentration of Sex Hormone-Binding Globulin (SHBG). SHBG is a critical glycoprotein synthesized primarily by the liver that binds and transports sex hormones, predominantly testosterone and estradiol, thereby regulating their crucial bioavailability. Understanding this correlation is vital because inflammation, often driven by metabolic dysfunction, can drastically alter SHBG levels, consequently changing the effective free hormone concentration at the target tissue level.
Origin
This concept is derived from the cross-disciplinary fields of endocrinology and immunology, recognizing that the liver, as the main site of SHBG synthesis, is highly responsive to the presence of inflammatory cytokines. Research demonstrating that elevated markers of systemic inflammation, such as C-Reactive Protein (CRP) and Interleukin-6 (IL-6), correlate with altered SHBG production established this fundamental link. The term highlights the profound metabolic-inflammatory influence on the precise regulation of sex hormones.
Mechanism
The mechanism involves pro-inflammatory cytokines acting as powerful signaling molecules that directly modulate the gene expression and synthesis of SHBG within hepatocytes, the primary liver cells. Chronic inflammation, which is frequently associated with underlying insulin resistance, can either upregulate or downregulate SHBG production, depending on the specific hormonal and metabolic context. This resulting change in binding protein concentration subsequently alters the crucial ratio of bound to unbound (free) sex hormones, directly impacting target tissue androgenic and estrogenic signaling.
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