Sex hormone binding globulin
Encyclopedia
Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein
that binds to sex hormones, to be specific, testosterone
and estradiol
. Other steroid hormone
s such as progesterone
, cortisol
, and other corticosteroids are bound by transcortin
.
. Only a small fraction is unbound, or "free," and thus biologically active and able to enter a cell
and activate its receptor
. The SHBG inhibits the function of these hormones. Thus, bioavailability of sex hormones is influenced by the level of SHBG. SHBG has a higher affinity for Dihydrotestosterone
than for Testosterone
or for Estradiol
, making it essential in women for regulating the bio-availability of Dihydrotestosterone
.
and is released into the bloodstream. 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 located on chromosome 17.
and insulin-like growth factor 1 (IGF-1) (see:milk). Also, high androgen
and transcortin
levels decrease SHBG, whereas high growth hormone
, estrogen
, and thyroxine
levels increase it.
However, recent evidence suggests that it is the liver's production of fats that reduces SHBG levels, not any direct effect of insulin and specific genetic mechanisms that do this have been found.
, diabetes, and hypothyroidism
. Conditions with high SHBG include pregnancy
, hyperthyroidism
, and anorexia nervosa
.
A free androgen index
expresses the ratio of testosterone to the sex hormone-binding globulin and can be used to summarize the activity of free testosterone.
The total testosterone is likely the most accurate measurement of testosterone levels and should always be measured at 8 o'clock in the morning. Sex hormone-binding globulin can be measured separate from the total fraction of testosterone.
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
that binds to sex hormones, to be specific, testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
and estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
. Other steroid hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s such as progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
, cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
, and other corticosteroids are bound by transcortin
Transcortin
Transcortin, also corticosteroid-binding globulin or CBG, is officially called serpin peptidase inhibitor, clade A , member 6.It is an alpha-globulin.-Binding:...
.
Transport of sex hormones
Testosterone and estradiol circulate in the bloodstream, bound mostly to SHBG and to some degree bound to serum albuminSerum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
. Only a small fraction is unbound, or "free," and thus biologically active and able to enter a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
and activate its receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
. The SHBG inhibits the function of these hormones. Thus, bioavailability of sex hormones is influenced by the level of SHBG. SHBG has a higher affinity for Dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
than for Testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
or for Estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
, making it essential in women for regulating the bio-availability of Dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
.
SHBG production
SHBG is produced mostly by the liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
and is released into the bloodstream. Other sites that produce SHBG include the brain, uterus, testes, and placenta. Testes-produced SHBG is called androgen-binding protein. The gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
for SHBG is located on chromosome 17.
Control
SHBG levels appear to be controlled by a delicate balance of enhancing and inhibiting factors. Its level is decreased by high levels of insulinInsulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
and insulin-like growth factor 1 (IGF-1) (see:milk). Also, high androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
and transcortin
Transcortin
Transcortin, also corticosteroid-binding globulin or CBG, is officially called serpin peptidase inhibitor, clade A , member 6.It is an alpha-globulin.-Binding:...
levels decrease SHBG, whereas high growth hormone
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
, estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
, and thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
levels increase it.
However, recent evidence suggests that it is the liver's production of fats that reduces SHBG levels, not any direct effect of insulin and specific genetic mechanisms that do this have been found.
Blood values
Reference ranges for blood tests for SHBG have been estimated to be:| Patient type | Range |
|---|---|
| Adult female, premenopausal | 40 - 120 nmol/L |
| Adult female, postmenopausal | 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 |
Conditions with high or low levels
Conditions with low SHBG include polycystic ovary syndromePolycystic ovary syndrome
Polycystic ovary syndrome is one of the most common female endocrine disorders. PCOS is a complex, heterogeneous disorder of uncertain aetiology, but there is strong evidence that it can to a large degree be classified as a genetic disease....
, diabetes, and hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
. Conditions with high SHBG include pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
, hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
, and anorexia nervosa
Anorexia nervosa
Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...
.
Measurement of sex hormones
When determining levels of circulating estradiol or testosterone, either a total measurement that includes the "free" and the bound fractions could be done, or only the "free" hormone could be measured.A free androgen index
Free androgen index
Free Androgen Index or FAI is a ratio used to determine abnormal androgen status in humans. The ratio is the total testosterone level divided by the sex hormone binding globulin level, and then multiplying by a constant, usually 100. The concentrations of testosterone and SHBG are normally...
expresses the ratio of testosterone to the sex hormone-binding globulin and can be used to summarize the activity of free testosterone.
The total testosterone is likely the most accurate measurement of testosterone levels and should always be measured at 8 o'clock in the morning. Sex hormone-binding globulin can be measured separate from the total fraction of testosterone.