Hormone-Binding Proteins

-
In Lecturio - 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 depending on the 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.
sex hormone-binding globulin
Image: “Sex hormone-binding globulin.” by Doxepine – Own work. License: Public Domain

Hormone-Binding Proteins

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 levels vary with their production in the liver which also varies with age, development and different physiological or pathophysiological conditions. Various pathologies are associated with disturbed production of SHBG and CBG and their abilities to bind hormones.
Binding proteinHormone
SHBGEstrogen, Testosterone
CBGCortisol
NeurophysinsVasopressin, Oxytocin
TBGThyroid hormone
IGFBPInsulin-like growth factors
VDBPCalcitriol

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 their affinity to SHBG is 4-5 times greater. It is bound to biologically active androgens and estrogens. Levels of SHBG 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. Other steroid hormones such as progesterone, cortisol and other corticosteroids are bund to transcortin.

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. Such drugs are:
  • 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. Such conditions cause increased level of androgens in the blood or increased transcortin levels. These include:
Drugs: Various drugs also decrease the production of these proteins. In this group fall

Thyroid-Binding Globulin (TBG)

Thyroid-binding globulin (TBG) is also formed in the liver and released into circulation to bind reversibly to the thyroid hormonespresent 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.
The normal levels of TBG in circulation is 1.1- 2.1 mg/dl. An increase in this level leads to increase in the total T4 and T3 levels but not an increase in the free hormone activity.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,is an alpha globulin secreted by the liver after expression of the SERPINA6 gene that encodes it. It carries various hormones in different levels as shown:
  • 75% of cortisol.
  • 78% of corticosterone.
  • 17% of aldosterone.
  • 18% of progesterone
Other hormones carried by transcortin include 4% f testosterone and 11-Deoxycorticosterone (DOC), which is an aldosterone precursor. It is the main determinant of circulating plasma cortisol levels in humans. CBG has maximum affinity for cortisol. More than 90% of the cortisol is carried by transcortin. Its level is raised in the prepubertal age, during 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 steroid 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. These conditions include:
  • 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:

Comentários

Enviar um comentário

Mensagens populares deste blogue

Hemorrhoids (Piles) — Symptoms and Treatment

-
Imagem
Hemorrhoids cushions are normal structures of the lower rectum.  They are very vascular and pathology develops when that vasculature becomes engorged (especially the veins). Itching and pain are common symptoms of hemorrhoid pathology. Hemorrhoids are classified on their origin relative to the dentate line: external (below the dentate line), internal (above the dentate line), and prolapsed internal hemorrhoids. Most hemorrhoids are treated with dietary modification (increase fiber) and stool softeners, but occasionally surgery is required. Table of Contents Definition of Hemorrhoids Epidemiology of Hemorrhoids Etiology of Hemorrhoids Pathology and Pathophysiology of Hemorrhoids Symptoms of Hemorrhoids Diagnosis of Hemorrhoids Differential Diagnoses of Hemorrhoids Therapy of Hemorrhoids Progression and Prognosis of Hemorrhoids Review Questions References Image : “Types of hemorrhoids” by WikipedianProlific and Mikae...
Ler mais

12 Cranial Nerves — Functions and Mnemonics

-
Imagem
Crania l nerves emerge directly via the spinal cord from the bony skull because they supply cranial structures or fulfill specific functions. During medical studies, cranial nerves are an essential element of the subjects of the brain and the nervous system. In the following, you will find a concise overview of the classification, the functions and the course of the 12 cranial nerves. Table of Contents Classification of Cranial Nerves List of Cranial Nerves Cranial nerve I: Olfactory Nerve Cranial nerve II: Optic Nerve Cranial Nerve III: Oculomotor Nerve Cranial Nerve IV: Trochlear Nerve Cranial Nerve V: Trigeminal Nerve Cranial Nerve VI: Abducent Nerve Cranial Nerve VII: Facial Nerve Cranial Nerve VIII: Vestibulocochlear Nerve Cranial Nerve IX: Glossopharyngeal Nerve Cranial Nerve X: Vagus Nerve Cranial Nerve XI: Accessory Nerve Cranial Nerve XII: Hypoglossal Nerve Overview of the 12 cranial nerves Review Questions References Image : “Cranial Nerves” by Br...
Ler mais

Nerve Tissue: Brain

-
Imagem
In LECTURIO :) - Table of Contents Introduction to the Brain The Cerebrum The Cerebellum The Meninges The Spinal Cord References Image :  “Skull and brain normal human diagram”  by Patrick J. Lynch. License:  CC BY 2.5 Introduction to the Brain The brain is the central organ of the human nervous system along with the spinal cord. It is made up of: The cerebrum Diencephalon, consisting of thalamus, hypothalamus and pituitary gland The cerebellum The brainstem- consisting of midbrain, pons and medulla Image :  “Introduction to Brain Structures”  by BruceBlaus. License:  CC BY 3.0 The organ weighs about 1400 grams on average in an adult. It is housed and protected by the skull bones which include the: Parietal Frontal Occipital Ethmoid Sphenoid bone The bones of the face Image :  “Cranial sutures shown from the top of the head”  by Xxjamesxx. License:  CC BY-SA 3.0 At birth, the paired an...
Ler mais