endocrinology

1. BY
Dr. Nusrat Tariq
Mechanism Of Action Of
Hormones

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
receptor activation.
3. Describe various intracellular second messenger
systems

3. Hormone receptors & their
activation:

6. Target Cells
Target cells refer to cells that contain
specific receptors (binding sites) for a
particular hormone.
 Once a hormone binds to receptors on a
target cell, a series of cellular events take
place.

10. Causes Of Down-regulation Of The
Receptors
(1) inactivation of the receptor molecules
(2) inactivation of the intracellular protein signaling
molecules
(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

11. RESULT ??

12. RESULT
Decreased target tissue’s
responsiveness to the
hormone

13. Up-regulation Of Receptors
 The stimulating hormone induces greater
than normal formation of receptor by the
target cell.
So greater availability of the receptor for
interaction with the hormone.

14. RESULT ??

15. RESULT
Increased target tissue’s
responsiveness to the
hormone

16. INTRACELLULAR SIGNALING AFTER
HORMONE RECEPTOR ACTIVATION

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
inactive state,
 In inactive state these subunits of G proteins
form a complex that binds guanosine
diphosphate (GDP) on the alpha subunit.

21. .
 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.

24. 2-enzyme Linked
Hormone Receptors

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
only once.
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
occasionally inactivated.

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
messenger
• 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

37. .

38. Intracellular Hormone Receptors and Activation
of Genes.
Steroid hormones, thyroid hormones and vit D, are
lipid soluble, they readily cross the cell membrane
and interact with receptors in the cytoplasm or
nucleus.
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
SIGNALLING MECHANISM
• 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).