Cortisol Binding Globulin (CBG), also known as transcortin, is a protein found in the bloodstream that plays a central role in managing the body’s stress response. Produced primarily in the liver, CBG’s main function is to transport cortisol, the body’s primary stress hormone. This protein regulates the availability of cortisol, influencing how the body responds to physiological demands.
The Role of CBG in Cortisol Regulation
CBG primarily regulates cortisol by binding to it, which renders the hormone inactive while it is in circulation. This bound form of cortisol cannot readily interact with cells or trigger biological effects. Only a small fraction of circulating cortisol remains “free” or unbound, and this free cortisol is the biologically active form.
This binding mechanism allows CBG to act as both a reservoir and a buffer for cortisol. When the body requires more active cortisol, such as during stress or inflammation, CBG can release its bound cortisol. CBG can release cortisol to target tissues. This dynamic process helps maintain stable levels of free cortisol, ensuring its availability when needed while preventing excessive exposure to the hormone. The binding is reversible and influenced by factors such as temperature, where higher temperatures can decrease CBG’s affinity for cortisol, increasing free cortisol availability, particularly at sites of inflammation.
Factors Influencing CBG Levels
CBG levels in the body can fluctuate due to a variety of physiological states, medications, and medical conditions. Estrogen, for instance, significantly influences CBG production, leading to increased levels. This is particularly evident during pregnancy, where CBG concentrations can rise two to threefold. Oral contraceptives, which contain estrogen, also cause a similar increase in CBG levels, influencing total cortisol but generally not significantly affecting free cortisol.
Conversely, certain conditions and medications can lead to a decrease in CBG levels. Since the liver is the primary site of CBG production, liver diseases such as cirrhosis or hepatitis can impair its synthesis, resulting in lower CBG concentrations. Thyroid disorders also play a role, with conditions like hypothyroidism potentially slowing cortisol metabolism and leading to increased free cortisol, while insulin can inhibit CBG synthesis.
Chronic inflammatory conditions can decrease CBG levels, sometimes due to inhibition of synthesis by inflammatory cytokines like IL-6. Additionally, genetic variations in the SERPINA6 gene, which provides instructions for making CBG, can lead to inherently low CBG levels. Glucocorticoid medications, which are synthetic cortisol, can also modulate circulating levels of CBG, often decreasing them with prolonged use.
Impact of Altered CBG Levels
Variations in CBG levels directly affect the amount of free, biologically active cortisol available to the body’s tissues. When CBG levels are abnormally high, more cortisol becomes bound, leading to a reduction in free cortisol. This can lead to symptoms of cortisol deficiency, such as fatigue or low blood pressure, even if total cortisol measurements appear normal. High CBG levels can also reduce the body’s ability to respond quickly to stress or inflammation.
Conversely, abnormally low CBG levels mean less cortisol is bound, resulting in an increase in free cortisol. This can contribute to symptoms resembling cortisol excess, often referred to as hypercortisolism or Cushing’s syndrome. Symptoms can include weight gain, muscle weakness, high blood sugar, and high blood pressure. Such changes in CBG can influence how the body manages stress and maintains metabolic balance. The interpretation of total cortisol measurements becomes less reliable when CBG levels are altered, making assessment of free cortisol important for understanding the body’s hormonal status.