Sex hormone-binding globulin

Helps to regulate levels of free sex hormones.

Primary function is the binding of circulating sex hormones to affect the bioavailable fraction and to sequester circulating estrogens and androgens from biologic activity.

Sex hormones, even bound to SHBG, may mediate cell surface signalling, cellular delivery and biologic activity of sex hormones.

Low circulating levels of SHBG associated with impaired glucose control, and plasma levels of sex hormones and risk of type 2 diabetes asociated with free sex hormones.

Blood levels of SHBG do have an impact on genetic susceptibility to type 2 diabetes development.

The sex hormones of the body, which are believed to play a part in type 2 diabetes development are regulated by a protein known as SHBG (sex hormone-binding globulin).

SHBG plasma levels are increased by anlbumin and corticosteroid-binding globulin (CBG).

Only a very small fraction of hormones, about 1-2% 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.

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.

DHEA is weakly bound to SHBG as well, but DHEA-S is not.

Androstenedione is not bound to SHBG either, and is instead bound solely to albumin.

SHBG is produced mostly by the liver and is released into the bloodstream, and other sites that produce SHBG include the brain, uterus, testes, and placenta.

Testes-produced SHBG is called androgen-binding protein.

The gene for SHBG is called Shbg and is located on chromosome 17 on the short arm between the bands 17p12→p13.

Overlapping on the complimentary DNA strand is the gene for spermidine/spermine N1-acetyltransferase family member 2 (SAT2).

There are eight exons, of which exon 1 has three variations called 1L, 1T and 1N which are triggered by three promoters: PL, PT and PN respectively.

SHBG comes with the 1L, 2, 3, 4, 5, 6, 7, and 8 exons connected together.

SHBG is homodimeric, meaning it has two identical peptide chains making up its structure.

SHBG has both enhancing and inhibiting hormonal influences.

SHBG decreases with high levels of insulin, growth hormone, insulin-like growth factor 1 (IGF-1), androgens, prolactin and transcortin.

High estrogen, and thyroxine levels cause SHBG to increase.

Obesity-related reductions in SHBG, related to evidence sugar or monosaccharide-induced hepatic lipogenesis, hepatic lipids and cytokines like TNF-alpha and Interleukin.

Anti-psoriatic drugs that inhibit TNF-alpha cause an increase in SHBG.

The common downstream mechanism for all of these, including the effect of thyroid hormones was downregulation of HNF4, hepatocyte nuclear factor 4.

Adult female, premenopausal SHBG level 40 – 120 nmol/L.

Adult female, postmenopausal levels 28 – 112 nmol/L.

Adult male 20 – 60 nmol/L.

Age 1 – 23 months 60 – 252 nmol/L.

Prepubertal (24m – 8y) 72 – 220 nmol/L.

Pubertal female 36 – 125 nmol/L.

Pubertal male 16 – 100 nmol/L.

SHBG levels are decreased by androgens, administration of anabolic steroids, polycystic ovary syndrome, hypothyroidism, obesity, Cushing’s syndrome, and acromegaly.

Low SHBG levels increase the probability of Type 2 Diabetes.

SHBG levels increase with estrogenic states such as oral contraceptives, pregnancy, hyperthyroidism, cirrhosis, anorexia nervosa, and certain drugs.

Long-term calorie restriction of more than 50 percent increases SHBG, while lowering free and total testosterone and estradiol.

DHEA-S, which lacks affinity for SHBG, is not affected by calorie restriction.

Polycystic Ovarian Syndrome is associated with insulin resistance and excess insulin lowers SHBG, which increases free testosterone levels.

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 decrease by half in girls and goes down to 25% in boys.

The change of SHBG at puberty is triggered by growth hormone, and its pulsatility differs in boys and girls.

In pregnant women in the last two thirds 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.

When checking serum estradiol or testosterone, a total level that includes free and bound fractions can be assayed, or the free portion may be measured alone.

A free androgen index expresses the ratio of testosterone to SHBG and can be used to summarize the activity of free testosterone.

Sex hormone-binding globulin can be measured separate from the total fraction of testosterone.

Leave a Reply

Your email address will not be published. Required fields are marked *