Proteins which bind to hormones and carry them to the target tissues to produce a desired effect are called hormone binding proteins (HBP). There are four major categories of HBPs on the basis of type of hormone they carry. These include: sex hormone binding proteins (SHBG), thyroid hormone binding proteins, cortisol binding proteins (CBG), steroid hormone binding protein – serum albumin.

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sex hormone-binding globulin

Image: “Sex hormone-binding globulin.” by Doxepine – Own work. License: Public Domain


Hormone Binding Proteins

All these proteins regulate the amount of hormone reaching the target cells. They also regulate the non-protein-bound or ‘free’ circulating active steroid hormones, which are considered as the ‘primary gatekeepers of steroid action’.

Albumin has limited specificity and affinity for steroids. SHBG and CBG unlike albumin, have a higher affinity for steroids and control the access to target tissues. SHBG binds with the androgens and estrogens while CBG binds glucocorticoids and progesterone. Both these binding proteins are glycoproteins but are structurally different.

Plasma SHBG and CBG level varies with their production in the liver which also varies with age, development and in different physiological or pathophysiological conditions. Various pathologies are associated with disturbed production of SHBG and CBG and their abilities to bind hormones.

Sex Hormone-Binding Globulin – SHBG

Sex hormone-binding protein is mainly produced in the liver and in small amounts in the brain, testes, uterus and placenta. This binding protein carries:

DHEA and androstenedione are also almost completely bound to albumin, but affinity of this binding protein is 4-5 times more than albumin. It is bound to biologically active androgens and estrogens. Levels of these proteins vary throughout life depending on the hormonal and metabolic factors. In males, more of the binding protein is occupied as compared to females because males have more androgens.

Conditions that cause an increase in production

In some conditions, the production of SHBG is increased. These include:

Drugs: various drugs also increase the production of these proteins like

  • Estrogens
  • Soy Isoflavones (licorice)
  • Synthetic progestins
  • Glucocorticoids
  • Growth hormone
  • Phenytoin

Conditions that cause a decrease in production

In some conditions, the production of SHBG is decreased like increased level of androgens in blood or increased transcortin levels. These include:

Drugs: various drugs also decrease the production of these proteins like

Thyroid-Binding Globulin (TBG)

Thyroid-binding globulin (TBG) is also formed in the liver. It binds to thyroid hormone present in the circulation, i.e. T3 and T4 primarily. Affinity of this binding protein is more for T4. Its affinity for various forms of thyroid hormones varies as: T4>T3>T1/T2. Newborns have a relatively very high level of TBG.

Conditions that cause an increase in production

Drugs:

  • Estrogens, circulating thyroid/free T3 + T4, Tamoxifen
    • Heroin
    • Mitotane
    • Methadone
    • Fluorouracil
    • Phenothiazines

Conditions that cause decrease in production

Drugs:

  • Testosterone
  • Valproic Acid
  • Phenytoin
  • Slow release nicotinic acid
  • Anabolic steroids
  • Glucocorticoids (Prednisone)

Corticosteroid-Binding Globulin (CBG) (or transcortin)

Corticosteroid-binding globulin (CBG), also called transcortin, carries corticol, progesterone, aldosterone and 11-Deoxycorticosterone (DOC), which is an aldosterone precursor. It is considered to be the main determinant of circulating plasma cortisol levels in humans. It has maximum affinity for cortisol. More than 90% of the cortisol is carried by transcortin. Its level is raised in the prepubertal age. Its production is increased in pregnancy and after use of estrogen as medication.

Production is decreased in the following conditions

  • Hypoproteinemia
  • Cushing’s syndrome
  • Corticoid treatment
  • Some cases of vitamin B12 deficiency
  • Septic shock
  • Drugs: various drugs can also reduce the production of transcortin like use of androgens.

Serum Albumin

Serum albumin is also a hormone-binding protein which is produced in the liver. It is one of the most abundant proteins in the blood. It binds with steroids hormones and other small lipophilic molecules non-specifically. It binds with multiple hormones including:

  • Thyroid hormones
  • Fat soluble hormones
  • Fatty acids to liver
  • Unconj. bilirubin
  • Various minerals

Albumin binds all the steroid hormones with the same affinity. Still, 99% of the albumin binding sites remain open. With age, albumin concentration is decreased. In some conditions, production of albumin is increased like

  • Dehydration
  • Congestive heart failure
  • Poor protein utilization
  • Glucocorticoid excess (adrenal overproduction of cortisol, tumor)

Drugs:

  • Anabolic steroids
  • Androgens
  • Growth hormone
  • Insulin

Similarly, in few conditions production of albumin is decreased. These include:

  • Kidney disease like nephrotic syndrome
  • Liver Disease like cirrhosis
  • Pregnancy
  • Severe malnutrition
  • Conditions of decreased nutrients:
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