2. LEARNING OBJECTIVES
By the end of this lecture you should be able to:
1. Describe location of various hormone receptors
and mechanism of their activation
2. Describe intracellular signaling after hormone
3. Describe various intracellular second messenger
6. Target Cells
Target cells refer to cells that contain
specific receptors (binding sites) for a
Once a hormone binds to receptors on a
target cell, a series of cellular events take
10. Causes Of Down-regulation Of The
(1) inactivation of the receptor molecules
(2) inactivation of the intracellular protein signaling
(3) Temporary sequestration of the receptor to the
inside of the cell
(4) destruction of the receptors by lysosomes after
they are internalized
(5) decreased production of the receptors
13. Up-regulation Of Receptors
The stimulating hormone induces greater
than normal formation of receptor by the
So greater availability of the receptor for
interaction with the hormone.
17. Types of Hormone Receptors.
• Ion channel linked hormone receptors
(membrane permeability mechanism)
• G protein linked hormone receptors
• Enzyme linked hormone receptors
18. Ion channel linked hormone receptors
(membrane permeability mechanism)
Neurotransmitters e.g. nor epinephrine,
combine with receptor→change in
structure of receptors→ opening or closing
of a channel for Na+, K+, or Ca++→
depolarization or hyperpolarization of post
synaptic membrane depending upon
nature of ions.
20. GG protein linked hormone receptors
protein linked hormone receptors Heterotrimeric GTP- binding proteins.
G protein have alpha, β, & γ subunits. In their
In inactive state these subunits of G proteins
form a complex that binds guanosine
diphosphate (GDP) on the alpha subunit.
When the receptor is activated, it undergoes a
conformational change that causes the GDP-bound trimeric
G protein to associate with the cytoplasmic part of the
receptor and to exchange GDP for (GTP).
Displacement of GDP by GTP causes the alpha subunit to
dissociate from the trimeric complex and to associate with
other intracellular signaling proteins;
these proteins, in turn, alter the activity of ion channels or
intracellular enzymessuch as adenylyl cyclase or
phospholipase C, which alters cell function
23. Types of G Protein
Inhibitory G proteins (denoted as Gi proteins).
Coupling of a hormone receptor to an inhibitory G protein
→decreased activity of intracellular enzymes.
Stimulatory G proteins (denoted as Gs proteins).
Coupling of a hormone receptor to a stimulatory G protein
→ increased activity of intracellular enzymes.
25. Enzyme linked hormone receptors
These receptors,when activated, function
directly as enzymes or are associated with
enzymes that they activate.
These receptors pass through the membrane
They have their hormone-binding site on the
outside of the cell membrane and their
catalytic or enzyme-binding site on the inside.
26. When the hormone binds to the extracellular
part of the receptor, an enzyme immediately
inside the cell membrane is activated (or
27. Enzyme linked hormone receptors
One example of an enzyme-linked receptor is
the leptin receptor .
The leptin receptor exists as a dimer
binding of leptin to the extracellular part of
the receptor alters its conformation, enabling
phosphorylation and activation of the
intracellular associated JAK2 molecules.
28. The activated JAK2 molecules then phosphorylate other
tyrosine residues within the leptin receptor–JAK2 complex
to mediate intracellular signaling.
The intracellular signals include phosphorylation of signal
transducer and activator of transcription (STAT) proteins,
which activates transcription by leptin target genes to
initiate protein synthesis.
Phosphorylation of JAK2 also leads to activation of other
intracellular enzyme pathways such as mitogen-activated
protein kinases (MAPK) and phosphatidylinositol 3-kinase
31. Second messenger system
• Adenylyl cyclase –C amp
• Cell membrane phospholipids second
• Calcium –calmodulin second messenger
36. HORMONES THAT ACT MAINLY ON
THE GENETIC MACHINERY OF THE CELL
• Steroid Hormones Increase Protein Synthesis
• Thyroid Hormones Increase Gene
Transcription in the Cell Nucleus
38. Intracellular Hormone Receptors and Activation
Steroid hormones, thyroid hormones and vit D, are
lipid soluble, they readily cross the cell membrane
and interact with receptors in the cytoplasm or
The activated hormone- receptor complex then
binds with a specific regulatory sequence of the
DNA called the hormone response element, and
activates or represses transcription of specific genes
and formation of mRNA
39. CARDINAL ELEMENTS OF A
• External signal (Hormone).
• Plasma membrane Receptor's).
• Transducer (e.g. G-proteins).
• Amplifier (e.g. Adenylate Cyclase).
• Second messenger (e. g. cyclic-AMP).
• Effectors (e.g. protein kinases).
• Response (e.g. glycogen mobilization).