Sex Hormone-Binding Carrier Proteins

•Sex Hormone Binding Globulin (SHBG)

•Corticosteroid Binding Globulin (CBG)

SHBG (sex hormone binding globulin)

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 (Corticosteroid-binding Globulin)

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