Endocrine System: Introduction

Fig. 1: Endocrine Glands


Neuroendocrine System: The nervous and endocrine systems coordinate together to maintain the homeostasis of the body. 

Table 1: Comparison of the functioning of the nervous system and the endocrine system.


A few of the mediators can act as both neurotransmitters and hormones. For example, norepinephrine is released as a neurotransmitter by sympathetic postganglionic neurons and as a hormone by chromaffin cells of the adrenal medullae. 

A certain part of the nervous system regulates the working of the endocrine system. 

The body contains two kinds of glands: 

  • Exocrine glands 
  • Endocrine glands 

Exocrine glands secrete their products into ducts that carry the secretions to the target site. For example sudoriferous (sweat), sebaceous (oil), mucous, and digestive glands. 

Endocrine glands release their products (hormones) into the interstitial fluid around the glands. The hormone diffuses into the blood capillaries from the interstitial fluid and reaches the target site via blood. 

The circulating amount of hormone is usually very low as it is needed only in small quantities. The endocrine glands include the pituitary, thyroid, parathyroid, adrenal, and pineal glands. 

Additionally, several organs and tissues contain cells that secrete hormones but are not exclusively categorized as endocrine glands. These include the hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine, skin, heart, adipose tissue, and placenta. 

All the endocrine glands and hormone-secreting cells constitute the endocrine system.

Endocrinology is the study of structure, function, diagnosis, and treatment of disorders of endocrine glands. 

Hormone Activity

Although the blood carries a particular hormone to all the cells, it affects only specific target cells. Only those target cells have a protein receptor that could bind and interact with that particular hormone. 

For example, thyroid-stimulating hormone (TSH) binds to receptors on cells of the thyroid gland, but it does not bind to cells of the ovaries because ovarian cells do not have TSH receptors. 

Like any other cell protein, receptors are constantly being synthesized and broken down. Normally, a target cell has 2000 to 100,000 receptors for a particular hormone. 

If a hormone is available in excess, the target cell can reduce the number of receptors (down-regulation) to render itself less sensitive to the hormone. For example, when certain cells of the testes are exposed to a high concentration of luteinizing hormone (LH), the number of LH receptors decreases. 

In contrast, up-regulation (increase in the number of receptors) makes a cell more sensitive to the low level of hormone. 

Circulating and Local Hormone

Fig. 2: Circulating and Local Hormones


Most endocrine hormones are circulating hormones—they reach their target site through blood. 

Other hormones, called local hormones, act locally either on neighboring cells or on the same cell that secreted them without entering into the blood.

Paracrine: the hormone that acts on the neighboring cells. 
 
Autocrine: the hormone that acts on the same cells that secret it. 

Interleukin- 2 (IL-2) is released by helper T cells (a type of T-lymphocyte) during immune responses. IL-2 activates nearby immune cells, a paracrine effect. It also functions as an autocrine to stimulate helper T cells to secrete more IL-2 and consequently reinforce the immune response. 

Nitric oxide (NO) is released by endothelial cells that line blood vessels. NO causes vasodilation by relaxing the nearby smooth muscles of blood vessels. This can cause lowering of blood pressure and also erection of the penis in males. The drug Viagra® (sildenafil) enhances the effects stimulated by nitric oxide in the penis. 

The action of local hormone is terminated quickly while the circulating hormones may remain in the blood and produce their effects for a few minutes to few hours. 

In time, circulating hormones are metabolized by the liver and excreted by the kidneys. In cases of hepatic or renal failure, excessive levels of hormones may accumulate in the blood. 

Chemical Classes of Hormones

Depending upon the solubility of hormones they can be divided into
Lipid-soluble hormones
Water-soluble hormones

Table 2: Lipid Soluble Hormones


Table 3: Water Soluble Hormones


Hormone Transport in the Blood

Water-soluble hormones are soluble in blood plasma and mostly circulated in free form (not attached to other molecules).

Most lipid-soluble hormones are circulated in bound form. These are bound to transport proteins that are synthesized by hepatocytes. 

The transport proteins have three functions: 
  1. They make lipid-soluble hormones temporarily water-soluble, thus increasing their solubility in blood. 
  2. They retard the excretion of small hormone molecules from the kidney.
  3. They act as reservoirs for lipid-soluble hormones.
In general, 0.1–10% of a lipid-soluble hormone is available in free form that can diffuse out of capillaries to interact with the receptor on target cells to produce the effect. 

Mechanism of Hormone Action

The effect of a hormone depends on both the hormone itself and the target cell. Different target cells respond differently to the same hormone. 

The hormone could induce synthesis of a new molecule, change in permeability of plasma membrane, enhance transportation of a molecule in and out of the target cell, modify the rate of a metabolic reaction, or cause contraction of the muscle. 

However, first of all, a hormone must bind with its receptor on the target cell. 

The receptors for lipid-soluble hormones are located inside the cytosol or nucleus of target cells. The receptors for water-soluble hormones are present on the plasma membrane of target cells.

Action of Lipid-Soluble Hormones

Fig. 3: Mechanism of Action of Lipid-Soluble Hormone

The mechanism of action of lipid-soluble hormone is as follows:
  1. Lipid soluble Hormone diffuses into the target cell.
  2. The activated receptor-hormone complex alters the gene expression.
  3. Newly formed mRNA directs the synthesis of specific proteins on ribosomes.
  4. New proteins alter the target cell’s activity.

Action of Water-Soluble Hormones

Water-soluble hormones can’t diffuse through the plasma membrane. They interact with receptors that protrude from the target cell surface. 

The receptors are integral transmembrane proteins in the plasma membrane. 

The interaction of hormones with the receptor leads to the generation of a second messenger inside the target cell.

Cyclic adenosine monophosphate (cyclic AMP) is the most common second messenger. 
Fig. 4: Mechanism of Action of Water-Soluble Hormones.


The action of a typical water-soluble hormone occurs as follows:
  1. The binding of hormone (first messenger) to its receptor activates the G protein, which activates adenylyl cyclase.
  2. Activated adenylyl cyclase converts ATP to cAMP.
  3. The cAMP serves as a second messenger to activate protein kinases.
  4. Activated protein kinases phosphorylate cellular proteins.
  5. Millions of phosphorylated proteins cause reactions that produce physiological responses.
  6. Phosphodiesterase inactivates cAMP to turn off the cell response.
Certain hormones such as growth hormone–inhibiting hormone (GHIH) produce their effect by decreasing cyclic AMP formation. The final effect will be a decrease in the activity of the phosphorylated protein.

Hormones can also utilize other second messengers such as calcium ions (Ca2+), cyclic guanosine monophosphate (cGMP), inositol trisphosphate (IP3), and diacylglycerol (DAG).

A particular hormone can produce diverse effects in different cells with the help of different second messengers.

Hormone Interactions

The response of a target cell to a hormone depends on 
  1. The hormone’s concentration in the blood. 
  2. The number of the target cell’s hormone receptors.
  3. The dominance of other hormones.
The effect of a hormone will be more if the concentration of the hormone or the number of the receptor increased.

Permissive effect: Sometimes, the presence of other hormones is required for a hormone to show its effect. This could be due to an increased number of receptors, increased synthesis of effector protein, or decreased hormone metabolism in the presence of the permissive hormone.

For example, the lipolysis (hydrolysis of triglycerides) effect of epinephrine is significantly enhanced in presence of thyroid (T3 and T4) hormones.

Synergistic effect: When the combined effect of two hormones acting together is greater than the sum of their individual effects. This happens when both hormones activate the same second messengers and consequently amplify the response.

For example, both glucagon and epinephrine increase the blood glucose concentration by promoting glycogenolysis (breakdown of glycogen) in liver cells. 

Antagonistic effect: If one hormone opposes the effect of another hormone. 

For example, insulin and glucagon are antagonistic in nature. Insulin stimulates the synthesis of glycogen while glucagon stimulates the breakdown of glucagon by hepatocytes. 




Acknowledgment
The images were created on www.biorender.com.


Reference:
Tortora, Gerard J., and Bryan H. Derrickson. Principles of anatomy and physiology. John Wiley & Sons, 2018.



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