Local Hormones Introduction .
[1]. Local hormones are the substances which act on the same area of their secretion or in immediate neighborhood.
[2]. The endocrine hormones are secreted in one place but execute their actions on some other remote place.
[3]. Local hormones are usually released in an inactive form and are activated by some conditions or substances.
Classification of Local Hormones .
Local hormones are classified into two types:
1. Hormones synthesized in tissues .
2. Hormones synthesized in blood.
Local Hormones Synthesized in Tissues .
Local hormones synthesized in the tissues are:
1. Prostaglandins and related substances .
2. Other local hormones synthesized in tissues.
Prostaglandins & Its related Hormones .
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| Synthesis of prostaglandins and related hormones . |
Prostaglandins and other hormones which are derived from arachidonic acid are collectively called eicosanoids.
The eicosanoids are:
1. Prostaglandins .
2. Thromboxanes .
3. Prostacyclin .
4. Leukotrienes .
5. Lipoxins .
Synthesis of eicosanoids .
[1]. Phospholipids of the cell membrane are released by the action of phospholipase A2 .
[2]. Phospholipids are converted into arachidonic acid.
[3]. Arachidonic acid is converted into an endoperoxide called prostaglandin G2 (PGG2 ), which is converted into prostaglandin H2 (PGH2 ).
[4]. PGH2 gives rise to prostaglandins, prostacyclin and Thromboxanes .
1. Prostaglandins .
[1]. Prostaglandins were first discovered and isolated from human semen by Ulf von Euler of Sweden, in 1930.
[2]. He thought that these hormones were secreted by prostate gland hence the name prostaglandins. However, now it is believed that almost all the tissues of the body including renal tissues synthesize prostaglandins.
Chemistry of Prostaglandins .
Prostaglandins are unsaturated fatty acids with a cyclopentane ring and 20 carbon atoms.
Synthesis of Prostaglandins .
Prostaglandins are synthesized from arachidonic acid.
Types of Prostaglandins .
A variety of prostaglandins are identified. Active forms of prostaglandins are PGA2 , PGD2 , PGE2 and PGF2 .
Actions of Prostaglandins .
Prostaglandins show variety of physiological actions in the body.
Various actions of prostaglandins are:
1. On blood: Prostaglandins accelerate the capacity of RBCs to pass through minute blood vessels.
2. On blood vessels: PGE2 causes vasodilatation.
3. On GI tract: The prostaglandins reduce gastric secretion. In experimental animals, prostaglandins inhibit the formation of peptic ulcer.
4. On respiratory system: PGE2 causes bronchodilatation.
5. On lipids: Some of the prostaglandins are antilipolytic agents. These hormones inhibit the release of free fatty acids from adipose tissue.
6. On nervous system: In brain, prostaglandins control or alter the actions of neurotransmitters .
7. On reproduction: Prostaglandins play an important role in regulating the reproductive cycle.
[7.1]. These hormones also cause degeneration of corpus luteum (luteolysis).
[7.2]. Prostaglandins increase the receptive capacity of cervical mucosa for sperms and cause reverse peristaltic movement of uterus and fallopian tubes during coitus. This in turn, increases the velocity of sperm transport in female genital tract.
[7.3]. Prostaglandins (PGE2 ) play an important role during parturition and facilitate labor by increasing the force of uterine contractions.
[7.4]. Prostaglandins are secreted from uterine tissues, fetal membranes and placenta. Their concentration increases in maternal blood and amniotic fluid at the time of labor.
[7.5]. Prostaglandins increase the force of uterine contractions by elevating the concentration of calcium ions in the smooth muscle fibers of uterus.
[7.6]. When injected intra-amniotically during pregnancy, prostaglandins induce abortion. When injected during last stages of pregnancy, prostaglandins induce labor.
8. On kidney: The prostaglandins stimulate juxtaglomerular apparatus and enhance the secretion of renin, diuresis and natriuresis.
Mode of action of prostaglandins .
Prostaglandins mainly act by the formation of second messenger cyclic AMP.
2. Thromboxanes .
Thromboxanes are derived from arachidonic acid.
Thromboxanes are of two types :
1. Thromboxane A2 , which is secreted in platelets .
2. Thromboxane B2 , the metabolite of thromboxane A2 .
Actions of Thromboxane A2 :
1. Causes vasoconstriction .
2. Plays an important role in hemostasis by accelerating aggregation of platelets .
3. Accelerates clot formation.
3. Prostacyclin .
[1]. Prostacyclin is also a derivative of arachidonic acid.
[2]. It is produced in the endothelial cells and smooth muscle cells of blood vessels.
Actions of Prostacyclin .
It causes vasodilatation and inhibits platelet aggregation.
4. Leukotrienes .
[1]. Leukotrienes are derived from arachidonic acid via 5hydroperoxyeicosatetraeonic acid (5HPETE).
[2]. Leukotrienes are the mediators of allergic responses. These hormones also promote inflammatory reactions.
[3]. The release of leukotrienes increases when some allergic agents combine with antibodies like IgE.
Actions of Leukotrienes .
Leukotrienes cause:
1. Bronchiolar constriction .
2. Arteriolar constriction .
3. Vascular permeability .
4. Attraction of neutrophils and eosinophils towards the site of inflammation.
5. Lipoxins .
[1]. Lipoxins are also derived from arachidonic acid via 15 hydroperoxyeicosatetraeonic acid (15HPETE).
[2]. Lipoxins are of two types namely, lipoxin A and lipoxin B.
Actions of Lipoxin .
Lipoxin A causes dilation of minute blood vessels. Both the types inhibit the cytotoxic effects of killer T cells.
Other Local Hormones Synthesized in Tissues .
In addition to prostaglandins and related hormonal substances, tissues secrete some more hormones
1. Acetylcholine .
2. Serotonin .
3. Histamine .
4. Substance P .
5. Heparin .
6. Leptin .
7. Gastrointestinal hormones.
1. Acetylcholine .
Acetylcholine is the cholinergic neurotransmitter . It is the transmitter substance at neuromuscular junction. It is also secreted by other nerve endings and other cells.
Source of secretion of Acetylcholine .
1. Presynaptic terminals .
2. Preganglionic parasympathetic nerve .
3. Postganglionic parasympathetic nerve .
4. Preganglionic sympathetic nerve .
5. Postganglionic sympathetic cholinergic nerves such as:
a. Nerves supplying eccrine sweat glands .
b. Sympathetic vasodilator nerves in skeletal muscle .
6. Nerves in amacrine cells of retina .
7. Mast cell .
8. Gastric mucosa .
9. Lungs .
10. Many regions of brain.
Actions of Acetylcholine .
1. Produces excitatory function of synapse by opening the sodium channels .
2. Activates smooth muscles in GI tract, urinary tract and skeletal muscles .
3. Inhibits cardiac function .
4. Causes vasodilatation.
Destruction of Acetylcholine .
[1]. Acetylcholine is very quick in action. Immediately after executing the action, it is destroyed by acetylcholinesterase.
[2]. This enzyme is present in basal lamina of the synaptic cleft.
2. Serotonin .
Serotonin is otherwise known as 5hydroxytryptamine.
Source of secretion of Serotonin .
Serotonin is secreted in the following structures:
1. Hypothalamus
2. Limbic system .
3. Cerebellum .
4. Spinal cord .
5. Retina .
6. Gastrointestinal tract .
7. Lungs .
8. Platelets.
Actions of Serotonin .
1. Is an inhibitory substance .
2. Inhibits impulses of pain sensation in posterior gray horn of spinal cord .
3. Causes mood depression and induces sleep .
4. Causes vasoconstriction.
3. Histamine .
Source of secretion of Histamine .
[1]. Histamine is secreted in nerve endings of hypothalamus, limbic cortex and other parts of cerebral cortex and spinal cord.
[2]. Histamine is also released from tissues during allergic condition, inflammation or damage.
Actions of Histamine .
1. It is an excitatory neurotransmitter substance .
2. Histamine released from tissues causes vasodilatation and enhances the capillary permeability for fluid and plasma proteins from blood into the affected tissues. So, the accumulation of fluid with proteins develops local edema .
3. In GI tract, histamine increases the motility.
4. Substance P .
Source of secretion i.
1. Nerve endings (first order neurons of pain pathway) in spinal cord and retina . ii.
2. GI tract (by the presence of chyme).
Actions of Substances P .
1. Substance P is the neurotransmitter for pain
2. It is also the neurotransmitter substance in GI tract. In GI tract, it increases the mixing and propulsive movements of small intestine.
5. Heparin .
Source of secretion of Heparin .
1. Mast cells .
2. Basophils.
Actions of Heparin .
Heparin is a naturally produced anticoagulant .
6. Leptin .
Leptin (in Greek, it means thin) is a protein hormone with 167 amino acids.
Source of secretion of Leptin .
Leptin is secreted by adipocytes in adipose tissues.
Actions of Leptin .
[1]. Leptin plays an important role in controlling the adipose tissue and food intake.
[2]. Leptin acts on hypothalamus and inhibits the feeding center, resulting in stoppage of food intake . [3]. At the same time, it also stimulates the metabolic reactions involved in utilization of fat stored in adipose tissue for energy.
[4]. Thus, the circulating leptin level informs the brain about the energy storage and the necessity to regulate metabolic reactions, food intake and body weight.
Local Hormones Produced in Blood .
Local hormones produced in the blood are:
1. Serotonin
2. Angiotensinogen
3. Kinins.
Kinins .
Kinins are biologically active protein hormones which are circulating in blood. Kinins are of two types: 1. Bradykinin .
2. Kallidin.
Along with other proteins of their family, kinins form the kinin system or kinin-kallikrein system.
Formation of Kinins .
Kinins are cleaved from their precursors which are of two types:
1. High-molecular-weight kinogen (HMW kinogen) – precursor of bradykinin .
2. Low-molecular-weight kinogen (LMW kinogen) – precursor of kallidin.
The cleavage of kinins from their precursors occurs by proteases called kallikreins, which are of two types, plasma kallikrein and tissue kallikrein.
Formation of bradykinin from HMW kinogen .
[1]. HMW kinogen is α-2-globulin secreted in liver. It is hydrolyzed by plasma kallikrein to form bradykinin.
[2]. Plasma kallikrein is circulating in blood in its inactive form called prekallikrein.
[3]. Prekallikrein is converted into active kallikrein by activated factor XII, which initiates the intrinsic pathway of blood coagulation. Kallikrein also activates factor XII .
Formation of kallidin LMW kinogen .
[1]. LMW kinogen is secreted in many tissues. It is hydrolyzed by tissue kallikrein to form kallidin, which is also known as lysylbradykinin.
[2]. Tissue kallikrein is present in many tissues like salivary glands, pancreas, intestine, sweat glands, kidneys and prostate.
Actions of Kinins .
Bradykinin:
1. Dilates the blood vessels and decreases the blood pressure. It is considered as a potent vasodilator .
2. Increases the blood flow throughout the body by its vasodilator action .
3. Increases permeability of capillaries during inflammatory conditions, resulting in edema in the affected area .
4. Stimulates pain receptors .
5. Causes contraction of extravascular smooth muscles, especially smooth muscles of intestine.
Kallidin:
Kallidin is also a vasodilator hormone.
Actions of Kallikreins .
1. Kallikreins hydrolyze the kinogens to form kinins .
2. Along with HMW kinogen, the plasma kallikrein activates factor XII during blood coagulation .
3. Kallikreins are potent vasodilators.
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