Local Hormones Synthesized In Tissues Notes

Local Hormones Introduction

• Local hormones are substances that act on the same area of their secretion or in the immediate neighborhood. The endocrine hormones are secreted in one place but execute their actions on some other remote place.
• Local hormones are produced in tissues and blood. These hormones are usually released in an inactive form and are activated by some conditions or substances.

Local hormones are classified into two types:

1. Hormones synthesized in tissues
2. Hormones synthesized in blood.

Read And Learn More: Medical Physiology Notes

Local Hormones Synthesized In Tissues

The local hormones synthesized in the tissues are:

1. Prostaglandins and related substances
2. Other local hormones synthesized in tissues.

Prostaglandins And Its 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: The phospholipids of the cell membrane are released by the action of phospholipase A₂. The phospholipids are converted into arachidonic acid. Arachidonic acid is converted into an endoperoxide called prostaglandin G₂ (PGG₂) which is converted into prostaglandin H₂(PG H₂). PGH₂ gives rise to prostaglandins, prostacyclin, and thromboxanes.

1. Prostaglandins: Prostaglandins were first discovered and isolated from human semen by Ulf von Euler of Sweden in 1930. He named them prostaglandins thinking that these hormones are from prostate gland. However, now it is believed that almost all the tissues of the body including renal tissues synthesize prostaglandins.
   • Chemistry: Prostaglandins are unsaturated fatty acids with a cyclopentane ring and 20 carbon atoms.
   • Synthesis: Prostaglandins are synthesized from arachidonic acid.
   • Types: A variety of prostaglandins are identified. Active forms of prostaglandins are PGA₂, PGD₂, PGE₂, and PGF₂.
   • Actions: 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 Gl tract: The prostaglandins reduce gastric secretion. In experimental animals, prostaglandins inhibit the formation of peptic ulcer.
     4. On the respiratory system: PGE₂ causes broncho-dilatation.
     5. On lipids: Some of the prostaglandins are antilipolytic agents. These hormones inhibit the release of free fatty acids from adipose tissue.
     6. On the nervous system: In the brain, prostaglandins control or alter the actions of neurotransmitters.
     7. On reproduction: Prostaglandins play an important role in regulating the reproductive cycle. These hormones also cause the degeneration of the corpus luteum (luteolysis). 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.
        • Prostaglandins ( PGE₂) play an important role during parturition and facilitate labor by increasing the force of uterine contractions. Prostaglandins are secreted from uterine tissues, fetal membranes, and placenta.
        • Their concentration increases in maternal blood and amniotic fluid at the time of labor. Prostaglandins increase the force of uterine contractions by elevating the concentration of calcium ions in the smooth muscle fibers of uterus.
        • When injected intra-amniotically during pregnancy, prostaglandins induce abortion. When injected during last stages of pregnancy, the prostaglandins induce labor,
     8. On kidney: The prostaglandins stimulate the juxtaglomerular apparatus and enhance the secretion of renin, diuresis, and natriuresis.
        • Mode of action of prostaglandins: Prostaglandins mainly act by the formation of the 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.
      • The thromboxane A₂ causes vasoconstriction. It plays an important role in hemostasis by accelerating the aggregation of platelets. It also accelerates clot formation.
3. Prostacyclin: Prostacyclin is also a derivative of arachidonic acid. It is produced in the endothelial cells and smooth muscle cells of blood vessels. It causes vasodilatation and inhibits platelet aggregation.
4. Leukotrienes
   • Leukotrienes are derived from arachidonic acid via 5-hydroperoxy eicosa-tetraeonic acid (5-HETE). Leukotrienes are the mediators of allergic responses. These hormones also promote inflammatory reactions.
   • The release of leukotrienes increases when some allergic agents combine with antibodies like IgE.
     • The leukotrienes cause:
       1. Bronchiolar constriction
       2. Arteriolar constriction
       3. Vascular permeability
       4. Attraction of neutrophils and eosinophils towards the site of inflammation.
5. Lipoxins
   • Lipoxins are also derived from arachidonic acid via 15-hydroperoxy eicosa-tetraeonic acid (15-HETE), Lipoxins are of two types namely, Lipoxin A and Lipoxin B.
   • Lipoxin A causes dilation of minute blood vessels Both 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 which are listed below.

1. Acetylcholine
2. Serotonin
3. Histamine
4. Substance P
5. Heparin
6. Leptin
7. Gl hormones.

 

1. Acetylcholine: Acetylcholine is the cholinergic neurotransmitter. It is the transmitter substance at neuromuscular junction. It is also released by the following nerve endings:
   1. Preganglionic parasympathetic nerve
   2. Postganglionic parasympathetic nerve
   3. Preganglionic sympathetic nerve
   4. Postganglionic sympathetic cholinergic nerves such as:
   5. Nerves supplying eccrine sweat glands
   6. Sympathetic vasodilator nerves in skeletal muscle
   7. Nerves in amacrine cells of retina
   8. Mast cell
   9. Gastric mucosa
   10. Lungs
   11. Many regions of brain.
       • Acetylcholine produces the excitatory function of the synapse by opening the sodium channels. Acetylcholine is very quick in action. It is also destroyed immediately after executing the action by the enzyme acetylcholinesterase. This enzyme is present in the basal lamina of the synaptic cleft.
       • Acetylcholine activates smooth muscles in Gl tract, urinary tract, and skeletal muscles. It inhibits cardiac function and causes vasodilatation.
2. Serotonin: It is otherwise known as 5-hydroxytryptamine. Serotonin is secreted in the following structures:
   1. Hypothalamus
   2. Limbic system
   3. Cerebellum
   4. Spinal cord
   5. Retina
   6. Gi tract
   7. Lungs
   8. Platelets
      • Serotonin is an inhibitory substance. It inhibits impulses of pain sensation in the posterior gray horn of spinal cord. It causes mood depression and sleep. It also causes vasoconstriction.
3. Histamine
   • It is secreted in nerve endings of the hypothalamus, limbic cortex, and other parts of the cerebral cortex. It is an excitatory neurotransmitter substance secreted in the spinal cord.
     Histamine is also released from tissues during allergic conditions, inflammation, or damage.
   • It causes vasodilatation and enhances the capillary permeability of fluid and plasma proteins from blood into the affected tissues. So, the accumulation of fluid with proteins develops local edema.
   • In the Gl tract, histamine increases motility.
4. Substance P
   • Substance P is the neurotransmitter for pain. It is secreted by nerve endings (first-order neurons of the pain pathway) in spinal cord and retina.
   • It is also the neurotransmitter substance in Gl tract. The presence of chyme in the duodenum causes the secretion of substance P. In Gl tract, it increases the mixing and propulsive movements of small intestine.
5. Heparin: Heparin is produced in mast cells. Mast cells are the wandering cells present immediately outside the capillaries in large number of tissues or organs, which contain more connective tissue. These wandering cells are abundant in liver and lungs. Basophils also secrete heparin. Heparin is a naturally produced anticoagulant.
6. Leptin
   • Leptin (in Greek it means thin) is a protein hormone with 167 amino acids. It is secreted by adipocytes in adipose tissues. Leptin plays an important role in controlling adipose tissue and food intake.
   • Leptin acts on the hypothalamus and inhibits the feeding center resulting in a stoppage of food intake. At the same time it also stimulates the metabolic reactions involved in the utilization of fat stored in adipose tissue for energy. Thus, the circulating leptin level informs the brain about energy storage and the necessity to regulate food intake and metabolic reactions.
7. Gastrointestinal Hormones: The gastrointestinal hormones are explained.

Local Hormones Produced In Blood

The local hormones produced in the blood are:

1. Serotonin
2. Angiotensinogen
3. Kinins.

Kinins: Kinins are biologically active protein hormones that are circulating in blood. The two kinins which are identified in human beings are:

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 kininogen (HMW kininogen) – the precursor of bradykinin
2. Low molecular weight kinogen (LMW kinogen) – the 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 kininogen
  • HMW kinogen is α₂ globulin secreted in liver. It is hydrolyzed by plasma kallikrein to form bradykinin.
  • Plasma kallikrein is circulating in blood in its inactive form called prekallikrein.
  • Prekallikrein is converted into active kallikrein by activated factor 12 which initiates the intrinsic pathway of blood coagulation. Kallikrein also activates factor 12.
• Formation of kallidin LMW kinogen
  • LMW kinogen is secreted in many tissues. It is hydrolyzed by tissue kallikrein to form kallidin which is also known as lysyl bradykinin.
  • Tissue kallikrein is present in many tissues like salivary glands, pancreas, intestine, sweat glands, kidneys, and prostate.

Actions of Bradykinin

• Bradykinin
  1. Dilates blood vessels and decreases 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. Is believed to cause contraction of extravascular smooth muscles especially smooth muscles of intestine.

Action of Kallidin: Kallidin is also a vasodilator hormone.

Actions of Kallikreins

1. Kallikreins hydrolyze the kinogens to form kinins
2. Along with HMW kininogen, the plasma kallikrein activates factor 12 during blood coagulation
3. Kallikreins are potent vasodilators.