•Sex Hormone Binding Globulin (SHBG)
•Corticosteroid Binding Globulin (CBG)
Aka. TeBG (TESTOSTERONE-estrogen Binding Globulin)
SHBG binds to estrogen and TESTOSTERONE in the blood(making them less bioavailable)
- Bioavailability of ESTRADIOLor TESTOSTERONE is determined by the level of SHBG - ESTRADIOL and TESTOSTERONE travel in the blood either strongly (but reversibly) bound to SHBG (ESTRADIOL 40%) or loosely bound to serum albumin (ESTRADIOL 59%).E.g. Only about 1-2% of circulating ESTRADIOL is "free"to enter a cell and activate its receptor.
SBGH level is delicately balanced by enhancing and inhibiting factors:
- SHBG is ▲ increased by: (makes otherwise unbound hormones LESS bioavailable)
• Liver disease, alcohol
• Hyperthyroidism - high levels of thyroxine (T3)
• Anorexia
• High levels of estrogen - E.g. use of HRT, oral contraceptives (metabolized by liver);
• High levels of GROWTH HORMONE
- SHBG is ▼ reduced by: (makes otherwise bound hormones MORE bioavailable)
• Higher circulating INSULIN levels - (note however, that recent evidence reveals that liver's fat production reduces SHBG, and not any direct effect of INSULIN);
• Obesity - obesity leads to high insulin levels, which causes a reduction in the liver's productionand circulating levels of SHBG (see note above); note that obesity also increases estrogen production in adipose cells via the aromatase enzyme; Thus, obesity can promote cancers such as breast and endometrial cancer -as estrogen becomes more bioavailable (free/unbound to SHBG) for its target tissues.
• Hypothyroidism;
• Androgens;
• Corticosteroid-binding globulin (CBG)
• INSULIN-LIKE GROWTH FACTOR-1(IGF-1)
• Cushing's disease;
• Soy - up to 10% reduction;
• Nettle root - contains compounds that bind to SHBG; nettle root is also anti-aromatase and therefore acts against estrogen production.
High/Low SHBG Conditions
- Low SHBG (making hormones MORE bioavailable) - seen in polycystic ovary syndrome, diabetes, hypothyroidism.
- High SHBG (making hormones LESS bioavailable) - seen in pregnancy, hyperthyroidism, anorexia nervosa. Recent research links high SHBG levels with breast and testicular cancer.
SHBG production sites
- SHBG is produced mainly in the liver cells and released into the bloodstream - other production sites are the brain, uterus, placenta and testes (where it is sometimes called androgen-binding protein).
CBG (a.k.a. transcortin) binds to PROGESTERONE , CORTISOL (and other corticosteroids)in the blood
- Bioavailability of PROGESTERONE , CORTISOL (and other corticosteroids) is determined by level of CBG
- PROGESTERONE is bound by CBG (~18%), albumin (~80%), SHBG (0.6%) and ~2% exists in the free state
Clinical Reproductive medicine and surgery, 2007
CBG level is balanced by enhancing and inhibiting factors:
- CBG is ▲ increased by: (makes otherwise unbound hormones LESS bioavailable)
• Estrogens / Pregnancy
- CBG is ▼ reduced by: (makes otherwise bound hormones MORE bioavailable)
• Cirrhosis (chronic liver disease);
• Alcohol
CBG production
- CBG is produced by the liver
