Mechanism of action of

hormones

Dr Asma Jabeen

• Identify the hormone receptors and Their activation

• Explain the intracellular signaling after hormone

receptor activation

• Describe the second messenger mechanisms

for mediating intracellular hormonal functions

• Identify the hormones that act mainly on the genetic

machinery of the cell

Learning Objectives

Hormone receptors

➢ Hormones bind to the specific receptors

at the target cell

➢ Cascade of reactions so that small conc.

can have large effect.

Location of hormone receptors

1. In or on the surface of the cell membrane:

Specific for protein, peptide and catecholamine

hormones.

2 . In the cell cytoplasm: Specific mostly for the steroid

hormones.

3. In the cell nucleus: thyroid hormones, and associated

with one or more chromosomes.

Regulation of number and sensitivity of

receptors

The no. of receptors does not remain constant.

Down-regulation:

The no. is decreased by increased hormone conc. and

increased binding with receptors. This is called down-

regulation which is due to:

❑ Inactivation of receptor molecules.

❑ Inactivation of intracellular signaling molecules.

Upregulation:

◼ Greater formation or greater availability of hormone

receptor for interaction with hormone.

❑ The target tissues become more sensitive to the

stimulating effects of hormone.

❑ Temp. sequestration of receptors.

❑ Destruction of receptors by lysosomes

❑ Decreased production of receptors.

Intracellular signaling after hormone

receptor activation

Types of interactions:

1. Ion channel-linked receptors

2. Protein linked hormone receptors

3. Enzyme-linked hormone

receptors

Ion channel linked receptors

• The neurotransmitter substances like

Acetylcholine and epinephrine combine with receptors →

Opening or closing a channel for one or more ions e.g.

sodium, potassium and calcium.

• The altered movements of these ions cause effects.

G- Protein linked Receptors

Enzyme Linked Hormone Receptors

❑ Proteins that pass through membrane

only once

❑ Hormone binding site on the outside and enzyme

binding site on the inside

❑ When Hormone binds to receptor an enzyme inside

cell membrane is activated

❑ Some such receptors have intrinsic enzyme activity

❑ Leptin receptor

Enzyme Linked Hormone Receptors

Intracellular hormone receptors

Second Messenger Mechanisms for mediating

Intracellular Hormonal Functions

The hormone activate a single type of

hormone receptor and rest of the hormone

action is done by second messenger.

1. cAMP second messenger system.

2. Calcium ions and associated calmodulin

3. Products of membrane phospholipid

breakdown

Adenylyl Cyclase-cAMP second messenger system

Formation of cAMP and its functions:

➢ The formation of cAMP within the cell

activates cAMP- dependent protein kinase

➢ It phosphorylates specific proteins in the

cell, triggering biochemical reactions

that ultimately lead to cell’s response to

hormone.

➢ The specific action of cAMP in the cell

depends on the intracellular machinery

Hormones which use cAMP second

messenger system

• ACTH TSH

• Angiotensin II Glucagon

(epithelial cells) Secretin

• Calcitonin Vasopressin

• Catecholamines

• CRH

• FSH

• LH

• Parathyroid hormone

The Cell Membrane Phospholipid

Second Messenger System

❑ Some hormones are attached to the receptors that activate

the enzyme phospholipase C

❑ This enzyme catalyzes the break down of membrane

phospholipids giving two different second messenger

products

1. Inositol Tri-phosphate ( IP 3 )

2. Diacylglycerol ( DAG )

❑ IP 3 mobilizes calcium ions from mitochondria

and ER that cause smooth muscle contraction and

changes in cell secretion.

❑ DAG activates protein kinase C which

phosphorylate a large no of protein leading to

response by the cell.

❑ DAG has Arachidonic acid - precursor of

prostaglandins.

Hormones that use Cell membrane phospholipid

second messenger system

• Angiotensin II (vascular smooth muscle)

• Catecholamines (alpha receptor)

• Gonadotropin releasing hormone (GnRH)

• Growth hormone releasing hormone

(GHRH)

• Oxytocin

• Thyroid-releasing hormone

• Vasopressin (V1 receptor, vascular

smooth muscle)

Calcium – Calmodulin Second messenger

system:

❑ This system operate in response to entry of calcium

into the cell which occurs due to

1. Changes in membrane potential that open calcium

channel

2. A hormone interacting with membrane receptor that

open calcium channel

❑ In the cell ,calcium bind with protein calmodulin.

when three or four have bound with calcium, it changes

its shape and initiates multiple effects in the cell

❑ There may be activation or inhibition of protein

Kinases - myosin kinase

Mechanism Of Action Of Steroid Hormones

The steroid hormones secreted by adrenal

cortex, ovaries and Testes cause protein

synthesis that act as enzymes, transport Proteins or

structural proteins.

1. Diffuses across the cell membrane and bind with

specific cytoplasmic protein receptor

2. Receptor protein – hormone complex

diffuses into the nucleus

3. The combination binds at specific sites on DNA

which activates transcription to form mRNA.

4. mRNA diffuses into the cytoplasm and

promotes translations at ribosomes to form new

proteins.

Mechanism Of Action Of Thyroid Hormones

Thyroid hormones bind directly with

receptor proteins in the nucleus. These

protein molecules are located within the

Chromosomal complex

Intracellular hormone receptors

Measurement of Hormone in the blood

Most hormones are present in very minute quantities

in the blood such as billionth of a

milligram(1 picogram). The methods used for measurement

of such small quantities are;

• Radioimmunoassay

• Enzyme linked immunosorbent Assay (ELISA)

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