Hormons act as integrating elements linking various regulatory mechanisms and metabolic processes in organs. They play the role of chemical intermediaries that ensure the transfer of signals that occur in different organs and in the central nervous system. Cells respond differently to hormones.
Through the adenylate cyclase system, the elements affect the rate of biochemical processes in the target cell. Consider this system in detail.
Physiological effect
The response of cells to the action of hormones depends on its chemical structure, as well as the type of cell it affects.
The concentration of hormones in the blood is quite low. To trigger the activation mechanism of the enzyme with the participation of the adenylate cyclase system, they must be recognized and then associated with receptors - special proteins with high specificity.
The physiological effect is determined by various factors, for example, the concentration of the hormone. It is determined by the speedinactivation during decay, occurring mainly in the liver, and the rate of its excretion along with metabolites. The physiological effect depends on the degree of affinity of the hormone for carrier proteins. Thyroid and steroid elements move along the bloodstream together with proteins. The number and type of receptors on target cells are also determining factors.
Stimulating Signals
The processes of synthesis and secretion of hormones are stimulated by internal and external impulses directed to the central nervous system. Neurons carry these signals to the hypothalamus. Here, due to them, the synthesis of statins and liberins (peptide releasing hormones) is stimulated. They, in turn, inhibit (suppress) or stimulate the synthesis and secretion of elements in the anterior pituitary gland. These chemical components are called triple hormones. They stimulate the production and secretion of elements in the peripheral endocrine glands.
Signs of hormones
Like other signaling molecules, these elements share a number of common features. Hormones:
- Excreted from the cells that produce them into the extracellular space.
- Not used as an energy source.
- They are not structural elements of cells.
- Have the ability to establish a specific relationship with cells that have specific receptors for a particular hormone.
- Differ in high biological activity. Even in small concentrations, hormones can effectively affect cells.
Target Cells
Their interaction with hormones is provided by special receptor proteins. They are found on the outer membrane, in the cytoplasm, on the nuclear membrane and other organelles.
There are two domains (sites) in any receptor protein. Due to them, the functions are implemented:
- Hormone recognition.
- Transformation and transmission of the received impulse to the cell.
Features of receptors
In one of the protein domains there is a site that is complementary (mutually complementary) to some element of the signal molecule. The binding of the receptor to it is similar to the process of formation of the enzyme-substrate complex and is determined by the affinity constant.
Most of the receptors are currently not well understood. This is due to the complexity of their isolation and purification, as well as the extremely low content of each type of receptor in the cells. However, it is known that the interaction of hormones with receptors is of a physicochemical nature. hydrophobic and electrostatic bonds are formed between them.
The interaction of a hormone and a receptor is accompanied by conformational changes in the latter. As a result, the complex of the signal molecule with the receptor is activated. Being in an active state, it is able to provoke a specific intracellular response to the incoming signal. When the synthesis or ability of receptors to interact with signaling molecules is impaired, diseases appear - endocrine disorders.
They may be related to:
- Lack of synthesis.
- Changes in the structure of receptor proteins (genetic disorders).
- Blocking receptors with antibodies.
Interaction types
They differ depending on the structure of the hormone molecule. If it is lipophilic, it is able to penetrate the lipid layer in the outer membrane of the targets. An example is steroid hormones. If the size of the molecule is significant, it cannot penetrate into the cell. Accordingly, receptors for lipophilic hormones are located inside the targets, and for hydrophilic hormones - outside, on the outer membrane.
Second intermediaries
Getting a response to a hormonal signal from hydrophilic molecules is provided by the intracellular mechanism of impulse transmission. It functions through the so-called second intermediaries. In contrast, hormone molecules are quite diverse in their shape.
Cyclic nucleotides (cGMP and cAMP), calmodulin (calcium-binding protein), calcium ions, inositol triphosphate, enzymes involved in the synthesis of cyclic nucleotides and protein phosphorylation act as "second messengers".
The action of hormones through the adenylate cyclase system
There are 2 main ways to transmit an impulse to target cells from signal elements:
- Adenylate ceclase (guanylate cyclase) system.
- Phosphoinositide mechanism.
The scheme of hormone action through the adenylate cyclase system involves: G protein, protein kinases,receptor protein, guanosine triphosphate, adenylate ceclase enzyme. In addition to these substances, ATP is also necessary for the normal functioning of the system.
Receptor, G protein, near which GTP and adenylate cyclase are located, are built into the cell membrane. These elements are in a dissociated state. After the formation of the complex of the signal molecule and the receptor protein, the conformation of the G protein changes. As a result, one of its subunits acquires the ability to interact with GTP.
The formed complex "G protein + GTP" activates adenylate cyclase. She, in turn, begins to transform ATP molecules into cAMP. It is able to activate specific enzymes - protein kinases. Due to this, the reactions of phosphorylation of various protein molecules with the participation of ATP are catalyzed. The composition of proteins at the same time includes the remains of phosphoric acid.
Due to the mechanism of action of hormones in the adenylate cyclase system, the activity of the phosphorylated protein changes. In different types of cells, proteins of different functional activity are affected: nuclear or membrane molecules, as well as enzymes. As a result of phosphorylation, proteins can become functionally active or inactive.
Adenylate cyclase system: biochemistry
Due to the interactions described above, the rate of biochemical processes in the target changes.
It is necessary to say about the insignificant duration of activation of the adenylate cyclase system. The brevity is due to the fact that the G protein, after binding to the enzymeGTPase activity begins to appear. It restores conformation after GTP hydrolysis and ceases to act on adenylate cyclase. This leads to the termination of the cAMP formation reaction.
Inhibition
In addition to the direct participants in the scheme of the adenylate cyclase system, in some targets there are receptors associated with G molecules, leading to inhibition of the enzyme. Adenylaceteclase is inhibited by the "GTP + G protein" complex.
When cAMP production stops, phosphorylation does not stop immediately. As long as the molecules exist, the activation of protein kinases will continue. To stop the action of cAMP, cells use a special enzyme - phosphodiesterase. It catalyses the hydrolysis of 3', 5'-cyclo-AMP to AMP.
Some compounds that have an inhibitory effect on phosphodiesterase (for example, theophylline, caffeine) help maintain and increase the concentration of cyclo-AMP. Under the influence of these substances, the duration of activation of the adenylate cyclase messenger system. In other words, the action of the hormone is enhanced.
Inositol triphosphate
Besides the adenylate cyclase signal transduction system, there is another signal transduction mechanism. It involves calcium ions and inositol triphosphate. The latter is a substance derived from inositol phosphatide (a complex lipid).
Inositol triphosphate is formed under the influence of phospholipase "C", a special enzyme that is activated during conformational changes in the intracellular domaincell membrane receptor.
Due to the action of this enzyme, the phosphoester bond of the phosphatidyl-inositol-4,5-bisphosphate molecule is hydrolyzed. As a result, inositol triphosphate and diacylglycerol are formed. Their formation leads, in turn, to an increase in the content of ionized calcium in the cell. This contributes to the activation of various calcium-dependent protein molecules, including protein kinases.
In this case, as with the launch of the adenylate cyclase system, protein phosphorylation acts as one of the stages of impulse transmission inside the cell. It leads to a physiological response of the cell to the effect of the hormone.
Connecting element
A special protein, calmodulin, is involved in the functioning of the phosphoinositide mechanism. A third of its composition is formed by negatively charged amino acids (Asp, Glu). In this regard, it is able to actively bind Ca+2.
There are 4 binding sites in one calmodulin molecule. As a result of interaction with Ca + 2, conformational changes begin in the calmodulin molecule. As a result, the Ca + 2-calmodulin complex acquires the ability to regulate the activity of many enzymes: phosphodiesterase, adenylate cyclase, Ca + 2, Mg + 2 - ATPase, as well as various protein kinases.
Nuances
In different cells, under the influence of the Ca + 2-calmodulin complex on the isoenzymes of one enzyme (for example, on adenylate cyclase of various types), in one case activation will be observed, and in the other - inhibition of cAMP formation. This is due to the fact that allosteric centers in isoenzymesmay include different amino acid radicals. Accordingly, their reaction to the impact of the complex will be different.
Extra
As you can see, "second messengers" are involved in the adenylate cyclase system and in the processes described above. When the phosphoinositide mechanism functions, they are:
- Cyclic nucleotides. As in the adenylate cyclase system, they are c-GMP and c-AMP.
- Calcium ions.
- Sa-calmodulin complex.
- Diacylglycerol.
- Inositol triphosphate. This element is also involved in signal transduction in the adenylate cyclase system.
The mechanisms of signaling from hormone molecules within targets involving the above mediators have several common features:
- One of the stages of information transfer is the process of protein phosphorylation.
- Activation stops under the influence of special mechanisms. They are launched by the process participants themselves (under the influence of negative feedback mechanisms).
Conclusion
Hormones act as the main humoral regulators of physiological functions in the body. They are produced in the endocrine glands or produced by specific endocrine cells. Hormones are released into the lymph, blood and have a distant (endocrine) effect on target cells.
Currently, the properties of these moleculeswell enough studied. The processes of their biosynthesis are known, as well as the main mechanisms of influence on the body. However, there are still many unsolved mysteries related to the peculiarities of the interaction of hormones and other compounds.
