Hormones Receptors Physiology Notes

Chemistry Of Hormones

Based on chemical nature the hormones are classified into three types:

1. Steroid hormones
2. Protein hormones
3. Derivatives of the amino acid, called tyrosine.

Read And Learn More: Medical Physiology Notes

1. Steroid Hormones: Steroid hormones are the hormones formed from cholesterol or its derivatives. Steroid hormones are secreted by the adrenal cortex, gonads, and placenta.
2. Protein Hormones: The preferred hormones are large or small peptides. Protein hormones are secreted by the pituitary gland, parathyroid glands, pancreas, and placenta (‘P’s).
3. Tyrosine Derivatives: There are two types of hormones, which are derivatives of the amino acid called tyrosine. Thyroid hormones and adrenal medullary hormones are derived from tyrosine.

Hormonal Action

Hormonal Action Introduction: Hormone does not act directly on cellular structures. First, the hormone combines with transmembrane receptors present on the target cells and forms a hormone-receptor complex. This hormone-receptor complex induces various changes or reactions in the target cells.

Hormone Receptors

• The hormone receptors are the large proteins present in the target cells. Each cell has thousands of receptors.
• The important characteristic feature of the receptors is that each receptor is highly specific for one single hormone, i.e. each receptor can combine with only one hormone.
• 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: The hormone receptors are situated either in cell membrane or cytoplasm or nucleus of the 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
  • Receptor proteins are not static components of the cell. Their number increases or decreases in various conditions.
  • Generally, when a hormone is secreted in excess, the number of receptors of that hormone decreases. This process is called down-regulation.
  • During the deficiency of the hormone, the number of receptors increases which is called up-regulation. When a hormone binds with the receptor, a hormone-receptor complex is formed.
  • This complex enters the target cell by means of endocytosis and executes the actions. The whole process is called internalization.
  • After internalization, some receptors are recycled, whereas many of them are degraded and replaced by newly formed receptors in the cell, which takes a long time.
  • So the number of receptors decreases when the hormone level increases.

Mechanism Of Hormonal Action: On the target cell, the hormone-receptor complex acts by any one of the following mechanisms:

1. By altering the permeability of the cell membrane: Neurotransmitters act by this mechanism
2. By activating the intracellular enzyme: Protein hormones and catecholamines act by this mechanism
3. By activating the gene: Thyroid hormones and steroid hormones act by this mechanism.

1. By Altering the Permeability of Cell Membrane

• The neurotransmitter substances in a synapse or neuromuscular junction act by changing the permeability of postsynaptic membrane.
• 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.
• The sequence of events during the action of acetylcholine:
  1. Acetylcholine moves through the presynaptic membrane, synaptic cleft, and reaches the postsynaptic membrane
  2. There, it combines with the receptor on the membrane and forms the hormone-receptor complex
  3. The hormone-receptor complex opens the ligand-gated sodium channels
  4. So, sodium ions enter the neuromuscular junction from ECF through the channels
  5. Sodium ions alter the resting membrane potential so that, endplate potential is developed.

2. By Activating the Intracellular Enzyme

• The mode of action of protein hormones and catecholamines is by activating the intracellular enzymes.
• The hormone, which acts on a target cell, is called the first messenger or chemical mediator. This hormone, in combination with the receptor forms the hormone – receptor complex.
• This in turn activates the enzymes of the cell and causes the formation of another substance called the second messenger or intracellular hormonal mediator.
• The second messenger produces the effects of the hormone inside the cells. The protein hormones and the catecholamines act through a second messenger. The most common second messenger is cyclic AMP.
• Cyclic AMP: Cyclic adenosine 3’5′-monophosphate or cyclic AMP or cAMP acts as a second messenger for the Protein hormones – pituitary hormones, parathormone and glucagon, and catecholamines.
• G proteins:
  • On the membrane of most of the target cells, the receptor proteins are in association with another type of membrane proteins called guanosine nucleotide binding proteins or G proteins. G proteins are located on the inner surface of cell membrane.
  • Each G protein molecule is made up of trimeric (three) subunits called α, β, and γ subunits. The α subunit is responsible for most of the biological actions.
  • It is bound with guanosin diphosphate (GDP) and forms α-GDP unit. The α subunit is also having the intrinsic enzyme activity called GTPase activity.
  • The β and γ subunits always bind together to form the β-γ dimmer. It can also bring about some actions. In the inactivated G protein both α-GDP unit and β-γ dimmer are united.
  • Sequence of events in the activation of second messenger:
    1. The 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
  • Both α-GTP unit and β-γ dimmer now activate the second messenger pathways When the action is over, a subunit hydrolyzes the attached GTP to GDP by its GTPase activity. This allows the reunion of a subunit with p-y dimmer and commencing a new cycle.

• Formation of cyclic AMP
  • 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.
  • The activated adenyl cyclase converts the adenosine triphosphate of the cytoplasm into cyclic adenosine monophosphate (cAMP), which is called the second messenger.
• Action of cyclic AMP
  • The second messenger, cAMP executes the actions of hormone inside the cell, by stimulating the enzymes like protein kinase A. The cAMP produces the response depending upon the function of the target cells through these enzymes. The responses may be one or more of the following:
    1. Contraction and relaxation of muscle fibers
    2. Alteration in the permeability of the 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.
• Calcium ions and calmodulin
  • Many hormones act by increasing the calcium ion, which acts as second messenger along with another protein called calmodulin or troponin C.
  • Calmodulin is present in smooth muscles and troponin C is present in skeletal muscles. The calcium-calmodulin complex activates various enzymes in the cell, which cause physiological responses.
  • The common enzyme activated by calcium – calmodulin complex is the myosin kinase in smooth muscle. The myosin kinase catalyses the reactions resulting in muscular contraction.
  • In the skeletal muscle, the calcium ions bind with troponin C, which is similar to calmodulin.
  • Inositol triphosphate (IP₃)
    • It is formed from phosphatidylinositol phosphate (PIP₂).
      The hormone-receptor complex activates the enzyme phospholipase which converts PIP₂ into IP₃.
    • IP₃ acts on protein kinase C and causes the physiological response by the release of calcium ions into the cytoplasm of target cell.
  • Diacylglycerol (DAG): It is also produced from PIP₂. It brings about the response via protein kinase C.
  • Cyclic guanosine monophosphate (cGMP): It functions like cAMP by acting on protein kinase – A.

3. By Acting on Genes

• The mechanism of action of thyroid and steroid hormones Is by acting on the genes of the target cells.
• Sequence on events during activation of genes:
• The hormone enters the interior of the cell and binds with receptors in cytoplasm (steroid hormone) or in nucleus (thyroid hormone) and forms hormone – receptor complex

This complex is transported towards the DNA

1. The hormone-receptor complex binds to DNA
2. This increases transcription of mRNA
3. The mRNA moves out of nucleus and reaches ribosomes and activates them
4. The activated ribosomes produce large quantities of proteins
5. These proteins produce the physiological responses in the target cells.