Hormone Introduction .
[1]. Hormones are chemical messengers, synthesized by endocrine glands.
[2]. Based on chemical nature, hormones are classified into three types :-
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| Classification of hormones depending upon chemical nature . |
1. Steroid hormones .
2. Protein hormones .
3. Derivatives of the amino acid called tyrosine.
Steroid Hormones .
[1]. Steroid hormones are the hormones synthesized from cholesterol or its derivatives.
[2]. Steroid hormones are secreted by adrenal cortex, gonads and placenta.
Protein Hormones .
[1]. Protein hormones are large or small peptides.
[2]. Protein hormones are secreted by pituitary gland, parathyroid glands, pancreas and placenta (‘P’s).
Tyrosine Derivatives .
Two types of hormones, namely thyroid hormones and adrenal medullary hormones are derived from the amino acid tyrosine.
Hormonal Action .
[1]. Hormone does not act directly on target cells.
[2]. First it combines with receptor present on the target cells and forms a hormone-receptor complex. [3]. This hormone receptor complex induces various changes or reactions in the target cells.
Hormone Receptors .
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| Situation of hormonal receptors . |
[1]. Hormone receptors are the large proteins present in the target cells.
[2]. Each cell has thousands of receptors.
[3]. Important characteristic feature of the receptors is that, each receptor is specific for one single hormone, i.e. each receptor can combine with only one hormone.
[4]. Thus, a hormone can act on a target cell, only if the target cell has the receptor for that particular hormone.
Situation of the Hormone Receptors .
Hormone receptors are situated either in cell membrane or cytoplasm or nucleus of the target cells as follows:
1. Cell membrane .
Receptors of protein hormones and adrenal medullary hormones (catecholamines) are situated in the cell membrane .
2. Cytoplasm .
Receptors of steroid hormones are situated in the cytoplasm of target cells
3. Nucleus .
Receptors of thyroid hormones are in the nucleus of the cell.
Regulation of Hormone Receptors .
[1]. Receptor proteins are not static components of the cell. Their number increases or decreases in various conditions.
[2]. Generally, when a hormone is secreted in excess, the number of receptors of that hormone decreases due to binding of hormone with receptors. This process is called down regulation.
[3]. During the deficiency of the hormone, the number of receptor increases, which is called upregulation .
[4]. Hormone in the form of hormone-receptor complex enters the target cell by means of endocytosis and executes the actions. The whole process is called internalization.
[5]. After internalization, some receptors are recycled, whereas many of them are degraded and new receptors are formed.
[6]. Formation of new receptors takes a long time. So, the number of receptors decreases when hormone level increases.
Mechanism of Hormonal Action .
[1]. Hormone does not act on the target cell directly.
[2]. It combines with receptor to form hormone-receptor complex. This complex executes the hormonal action by any one of the following mechanisms:
1. By altering permeability of cell membrane .
2. By activating intracellular enzyme .
3. By acting on genes.
By Altering Permeability of Cell membrane .
[1]. Neurotransmitters in synapse or neuromuscular junction act by changing the permeability of postsynaptic membrane.
[2]. For example, in a neuromuscular junction, when an impulse (action potential) reaches the axon terminal of the motor nerve, acetylcholine is released from the vesicles.
[3]. Acetylcholine increases the permeability of the postsynaptic membrane for sodium by opening the ligand-gated sodium channels.
[4]. So, sodium ions enter the neuromuscular junction from ECF through the channels and cause the development of endplate potential.
By Activating Intracellular Enzyme .
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| Mode of action of protein hormones and catecholamines . |
Protein hormones and the catecholamines act by activating the intracellular enzymes.
First Messenger .
[1]. The hormone which acts on a target cell, is called first messenger or chemical mediator.
[2]. It combines with the receptor and forms hormone-receptor complex.
Second Messenger .
[1]. Hormone-receptor complex activates the enzymes of the cell and causes the formation of another substance called the second messenger or intracellular hormonal mediator.
[2]. Second messenger produces the effects of the hormone inside the cells. Protein hormones and the catecholamines act through second messenger. Most common second messenger is cyclic AMP.
Cyclic AMP .
Cyclic AMP, cAMP or cyclic adenosine 3’5’- monophosphate acts as a second messenger for protein hormones and catecholamines.
Formation of cAMP – Role of G proteins .
[1]. G proteins or guanosine nucleotide-binding proteins are the membrane proteins situated on the inner surface of cell membrane.
[2]. These proteins play an important role in the formation of cAMP .
[3]. Each G protein molecule is made up of trimeric (three) subunits called α, β and γ subunits.
[4]. The α-subunit is responsible for most of the biological actions. It is bound with guanosine diphosphate (GDP) and forms α-GDP unit.
[5]. The α-subunit is also having the intrinsic enzyme activity called GTPase activity.
[6]. The β and γ subunits always bind together to form the β-γ dimmer. It can also bring about some actions.
[7]. In the inactivated G protein, both α-GDP unit and β-γ dimmer are united .
Sequence of events in the formation of cAMP .
[1] . Hormone binds with the receptor in the cell membrane and forms the hormone-receptor complex
[2] . It activates the G protein
[3] . G protein releases GDP from α-GDP unit
[4] . The α-subunit now binds with a new molecule of GTP, i.e. the GDP is exchanged for GTP .
[5] . This exchange triggers the dissociation of α-GTP unit and β-γ dimmer from the receptor
[6]. Both α-GTP unit and β-γ dimmer now activate the second messenger pathways .
[7]. The α-GTP unit activates the enzyme adenyl cyclase, which is also present in the cell membrane. Most of the adenyl cyclase protrudes into the cytoplasm of the cell from inner surface of the cell membrane .
[8]. Activated adenyl cyclase converts the adenosine triphosphate of the cytoplasm into cyclic adenosine monophosphate (cAMP) .
When the action is over, α-subunit hydrolyzes the attached GTP to GDP by its GTPase activity. This allows the reunion of α-subunit with β-γ dimmer and commencing a new cycle .
Actions of cAMP .
[1]. Cyclic AMP executes the actions of hormone inside the cell by stimulating the enzymes like protein kinase A.
[2]. Cyclic AMP produces the response, depending upon the function of the target cells through these enzymes.
Response produced by cAMP .
Cyclic AMP produces one or more of the following responses :-
[1]. Contraction and relaxation of muscle fibers .
[2]. Alteration in the permeability of cell membrane .
[3]. Synthesis of substances inside the cell .
[4]. Secretion or release of substances by target cell .
[5]. Other physiological activities of the target cell.
Other Second Messengers .
In addition to cAMP, some other substances also act like second messengers for some of the hormones in target cells.
i. Calcium ions and calmodulin .
[1]. Many hormones act by increasing the calcium ion, which functions as second messenger along with another protein called calmodulin or troponin C.
[2]. Calmodulin is present in smooth muscles and troponin C is present in skeletal muscles.
[3]. Calcium-calmodulin complex activates various enzymes in the cell, which cause the physiological responses.
[4]. Common enzyme activated by calcium-calmodulin complex is the myosin kinase in smooth muscle.
[5]. Myosin kinase catalyses the reactions, resulting in muscular contraction .
[6]. In the skeletal muscle, calcium ions bind with troponin C, which is similar to calmodulin .
ii. Inositol triphosphate .
[1]. Inositol triphosphate (IP3 ) is formed from phosphatidylinositol bi-phosphate (PIP2 ).
[2]. Hormone-receptor complex activates the enzyme phospholipase, which converts PIP2 into IP3 .
[3]. IP3 acts on protein kinase C and causes the physiological response by the release of calcium ions into the cytoplasm of target cell.
iii. Diacylglycerol .
Diacylglycerol (DAG) is also produced from PIP2 . It acts via protein kinase C.
iv. Cyclic guanosine monophosphate .
Cyclic guanosine monophosphate (cGMP) functions like c-AMP by acting on protein kinase A.
By Acting on Genes .
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| Mode of action of steroid hormones . |
Thyroid and steroid hormones execute their function by acting on genes in the target cells .
Sequence of Events during Activation of Genes .
[1]. Hormone enters the interior of cell and binds with receptor in cytoplasm (steroid hormone) or in nucleus (thyroid hormone) and forms hormone receptor complex .
[2]. Hormone-receptor complex moves towards the DNA and binds with DNA .
[3]. This increases transcription of mRNA .
[4]. The mRNA moves out of nucleus and reaches ribosomes and activates them .
[5]. Activated ribosomes produce large quantities of proteins .
[6]. These proteins produce physiological responses in the target cells .
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