Hormone Mechanisms of action: We will divide these mechanisms based on two different types of hormones, the hydrophilic and hydrophobic hormones1-6.
Hormone Mechanisms of action is the Lesson 3 of Chapter 1 (Introduction to Endocrinology, the Endocrine system). We will begin this lesson today as the first of 2 parts: hydrophilic (part 1) and hydrophobic (part 2) hormones.
Hormone Mechanisms of action part I: hydrophilic hormones
Hormones are grouped into three structural classes: amines or amino acid-derived hormones, peptide- or protein-based hormones, and lipid-based hormones7. However, from a mechanistic perspective, we can group all these classes into two major categories: the hydrophilic and hydrophobic hormones.
Structures of the hydrophilic hormones
- Amines or amino acid derivatives8,9. These hydrophilic hormones are derived from tyrosine. They comprise of the catecholamines (epinephrine, norepinephrine). Not all amino acid-derived or amine hormones (g., thyroid hormone) are hydrophilic.
- The polypeptide/protein hormones10-15 consist of hormones made of several amino acids, and this category includes polymers of different length. These include insulin16, glucagon17, somatostatin17, vasopressin2,18, and many other protein hormones13,19.
Hydrophilic means that they like water, and all hydrophilic hormones act by a similar mechanism. The other group is composed of hydrophobic hormones, which will be covered in the next lesson of Chapter I.
Let us take a closer look at each class of hormones based on structure and mechanisms of action. Let us recall what happens when hormones are secreted. Contrary to what you may have heard, hormones are not secreted directly into the bloodstream. Hormones are synthesized inside the cell and then secreted into the extracellular milieu. Once released, the hormone is exposed to the vasculature of the tissue and typically absorbed through the capillaries into the bloodstream. This is like a highway system. The hormones cruise through the systemic circulation and exit at multiple points to the extracellular matrices until they reach their target tissue or cells. What this means is that the hormone may exit the bloodstream to end up at a wrong target tissue just as a driver who takes the wrong exit on a highway. The hormone is reabsorbed into the blood till it reaches the correct target.
Endocrine system Hormone Mechanisms of action: Hydrophilic hormones
Hydrophilic hormones, as you can imagine, has no problem dissolving in an aqueous environment such as the blood. Therefore, they can be easily transported in the systemic circulation. Once the hormone reaches the right target organ, tissue, or cell, it can now interact with the cell. Remember that the cell membrane carries phospholipids. While the hydrophilic hormone may interact with the head of the lipid on the cell surface, it would have to go through the lipid tails to cross the cell membrane. Therefore, the hydrophilic hormone would have to go through a “hostile” environment. How does it do that? Well, it just does not! The hormone recognizes its target via a specific receptor, which must be on the target cell surface. Once the hormone arrives at its destination, it recognizes its receptor on the target cell, which “tells” the hormone that it is at the correct destination. The hormone then binds to its receptor on the cell surface. A molecule, such as a hormone, which binds a receptor, is called a ligand. This is a term you will hear quite often. This binding causes the receptor to change shape and send a signal inside the cell. This is why we call this form of messaging system a signaling pathway.
Endocrine System Hormone Mechanisms of action: The role of hormone receptors
Think of a cell receptor as a gatekeeper. It only allows a specific message to be signaled through the cell. As a result, the ligand has to be able to communicate with the receptor to activate that signaling pathway. As you can imagine, since the receptor has to send a message, it must initiate a chain reaction to carry the message through. Therefore, the receptor must be in contact with other molecules. One such molecule is commonly a G protein, and receptors coupled to a G protein are called G protein-coupled receptors. Since the receptor has to communicate with the hormone outside the cell and another molecule inside the cell, then the receptor has to span the cell membrane. For the message to reach its destination, the receptor has to activate its G protein and let it go to carry on that message.
Endocrine System Hormone Mechanisms of action: Hydrophilic hormones use a second messenger system
Once released from the receptor, the G protein will bind to another protein. In this case, it will bind and activate an enzyme called adenylate cyclase (AC). The AC then converts an ATP molecule into cyclic AMP (cAMP). This cAMP can now lead the way to the activation of various enzymes or other proteins. We call cAMP a second messenger. Now you can picture a hormone as a courier who drops a package to a security concierge at a specific gate, the receptor. Imagine the cell surface hormone receptor as a security guard who cannot leave his/her post. In this case, the receptor (security guard) has strict instruction not to let any messenger in. Therefore, the receptor takes the message from the first messenger (the hormone) and transfers it to a second messenger via his/her assistant, the G protein-dependent AC. AC now transfers the message through the conversion of ATP to cAMP (the 2nd messenger). The second messenger will now trigger the activation of other proteins or enzymes to allow a specific action. This is how the hydrophilic hormones exert their actions via a second-messenger system. This is like a switch that is turned on or off, and it is relatively fast acting. Neurotransmitters act this way as neuroendocrine hormones, which are hydrophilic. That is, in a nutshell, the hydrophilic hormone mechanisms of action.
In summary, hydrophilic hormones are soluble in aqueous environments. They are secreted in the extracellular milieu and absorbed into the blood, which takes them to their target cells. The hormones then bind to their receptors at the cell surface. The receptor changes shape and releases its bound G protein. The G protein activates AC, which converts ATP into the second messenger cAMP. This second messenger then carries the message to other molecules, resulting in specific actions. This system is fast-acting because it works like an on/off switch that does not require the synthesis of new molecules. It just activates pre-existing factors for a quick response. That is in general how hydrophilic hormones work. What about hydrophobic hormones?
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