SEX HORMONE BINDING GLOBULIN (SHBG)
ADULT MALE 20-60 nmol/L
Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. Other steroid hormones such as progesterone, cortisol, and other corticosteroids are bound to trancortin
Testosterone and estradiol circulate in the bloodstream, loosely bound mostly to serum albumin (~54%), and to a lesser extent bound tightly to SHBG (~44%). Only a very small fraction of about 1 to 2% is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. SHBG inhibits the function of these hormones. Thus, bioavailability of sex hormones is influenced by the level of SHBG. The relative binding affinity of various sex steroids for SHBG is dihydrotestosterone (DHT), testosterone> androstenediol> estradiol > > estrone.
DHT binds to SHBG with about 5 times the affinity of testosterone and about 20 times the affinity of estradiol. Dehydroepiandrosterone (DHEA) is weakly bound to SHBG, But dehydroepiandersterone sulfate is not bound to SHBG. Androstenedione is not bound to SHBG either, and is instead bound solely to albumin. Estrone is also poorly bound by SHBG. Less than 1% of progresterone is bound to SHBG.
SHBG levels are usually about twice as high in women than in men. In women, SHBG serves to limit exposure to both androgens and estrogens. Low SHBG levels in women have been associated with hyperandrogenism and endometrial cancer due to heightened exposure to androgens and estrogens, respectively.
SHBG is produced mostly by the liver and is released into the bloodstream. Other sites that produce SHBG include the brain, uterus, testes, and placenta.
Testes-also produce SHBG and it is called androgen-binding protein.
SHBG has both enhancing and inhibiting hormonal influences. It decreases with high levels of insulin, growth hormone, IGF 1, androgens, prolactin and transcortin. High estrogen and thyroxine levels cause it to increase as well.
SHBG levels are decreased by androgens, administration of anabolic steroids, polycystic ovary syndrome, hypothyroidism, obesity, Cushing syndrome and acromegaly. Low SHBG levels increase the probability of type two diabetes.
SHBG levels increase with estrogenic states, oral contraceptives, pregnancy, hyperthyroidism, cirrhosis, anorexia nervosa. Long-term calorie restriction of more than 50 percent increases SHBG, while lowering free and total testosterone and estradiol.
In the womb the human fetus has a low level of SHBG allowing increased activity of sex hormones. After birth, the SHBG level rises and remains at a high level throughout childhood. At puberty the SHBG level halves in girls and goes down to a quarter in boys. The change at puberty is triggered by growth hormone, and its pulsatility differs in boys and girls. In pregnant women in the third trimester of pregnancy the SHBG level escalates to five to ten times the usual level for a woman.
Obese girls are more likely to have an early menarche due to lower levels of SHBG. Anorexia or a lean physique in women leads to higher SHBG levels, which in turn can lead to amenorrhea.
Low levels of SHBG can be related to:
- Obesity
- Type 2 diabetes
- Hypothyroidism
- Acromegaly, or too much growth hormone, causing body tissues to grow larger over time
High levels of SHBG can be related to:
- Hepatitis
- Hyperthyroidism
- HIV
- Anticonvulsants, or medicines used to treat seizures