HORMONE ACTION

&
SIGNAL TRANSDUCTION

Lecturer:
Dr. Geraldine Jaca-Corporal
Hormones
 Substances that carry information from
sensor cells, which sense changes in the
environment, to target cells, which respond
to changes.

 Classified according to:

a. proximity of site synthesis to site of action
b. chemical structure
c. degree of water solubility
 Hormones
Site of Synthesis:
1. Endocrine Hormones –
synthesized by endocrine
glands & transported by the
blood to target cells.
e.g. testosterone, estrogen

2. Paracrine Hormones –
synthesized near their targets
of action
e.g. growth factors, somatostatin,
histamine
 Hormones
Site of Synthesis:

3. Autocrine Hormones –
affect the cells that
synthesize them

e.g. cytokine interleukin-1 in

monocytes
Hormones
Chemical Structure:
a. Proteins or Peptides – synthesized as large
precursors that undergo processing & secretion.
e.g. insulin, glucagon

b. Amino Acid Derivatives

e.g. Catecholamines, thyroid hormones

c. Fatty Acid Derivatives

e.g. eicosanoids
Hormones
Chemical Structure:

d. Cholesterol derivatives
e.g. steroids

e. Gases
e.g. nitrous oxide
 Hormones
Water Solubility:
1. GROUP 1 or Lipophilic Hormones
- bind to intracellular receptors with
subsequent modulation of gene
expression by the hormone-receptor
complex.

- hormone-receptor interaction: in
cytoplasm or nucleus

- e.g. glucocorticoid, thyroid

hormones, testosterone,
progesterone
 Hormones
Water Solubility:

2. GROUP 2 or Hydrophilic
Hormones
- bind to a receptor molecule
on the outer surface of the cell

- e.g. human growth

hormone, thyroid stimulating
hormone
Hormones in response to
stimulus
SIGNAL GENERATION

Group 1 or  slower to act

Lipophilic Hormones
 longer duration of
action (hours to
bind to intracellular
receptors (cytoplasm days)
or nucleus)

structural change
occurs in the receptor

cellular response
Glucocorticoid
Thyroid hormones & retinoids
Hormone Response Elements (HREs)
HORMONE or HORMONE DNA SEQUENCE
EFFECTOR RESPONSE
ELEMENT (HRE)
Glucocorticoids GRE
Progestins PRE GGTACA NNN TGTTCT
Mineralocorticoids MRE
Androgens ARE

AGGTCA --- TGA/TCCT

Estrogens ERE

Thyroid hormone TRE AGGTCA N3,4,5 AGGTCA

Retinoic Acid RARE
Vitamin D VDRE

cAMP CRE TGACGTCA

GROUP 2 or HYDROPHILIC
HORMONES

 initiate response w/out entering the

cell
 receptors are large, integral membrane
proteins w/ specificity & high affinity
 more rapid response
 shorter duration of action (seconds to
hours)
 bind to G protein-coupled receptors
(GPCR)
G PROTEIN-COUPLED
RECEPTORS (GPCR)
- 7 membrane-spanning
domains
- 3 subunits:
1. α – binds guanosine
diphosphate (GDP) or
guanosine triphosphate
(GTP)
2. β bind to α subunit
3. γ
G PROTEIN-COUPLED
RECEPTORS (GPCR)
G PROTEIN-COUPLED
RECEPTORS (GPCR)

 Type:
1. Gs – stimulates
adenylyl cyclase
2. Gi – inhibits
adenylyl cyclase
3. Gq – stimulates
enyzyme
phospholipase C
Cylic Adenosine
Monophosphate (cAMP)

 1st intracellular signal identified in

mammalian cells

 nucleotide formed from ATP catalyzed by

adenylyl cyclase.
Adenylyl cyclase

 Catalyzes the formation of cAMP from

ATP
 Consists of a receptor – Rs or Ri and a
regulatory complex – Gs or Gi
Cholera toxin

 Enzyme produced by the

bacterium Vibrio cholerae

 Action:
cholera toxin modifies the
α subunit , blocking the
hydrolysis of GTP to GDP
α-GTP remains in the
active form.
Cholera toxin

 Result:
persistently high level of
cAMP epithelial cells
of the intestine transport
Na ions & water into the
intestinal lumen
severe diarrhea
 Hormones That Hormones That
Stimulate Adenylyl Inhibit Adenylyl Cyclase
Cyclase (Hs ) (Hs )

 ACTH  Acetylcholine
 ADH  α2- Adrenergics
 β –Adrenergics  Angiotensin II
 Calcitonin  Somatostatin
 CRH
 FSH
 Glucagon
 hCG
 LH, PTH
 TSH, LPH, MSH
Protein Kinase

 cAMP binds to a protein kinase A which

consists of 2 regulatory subunits (R) and 2
catalytic subunits (C).

4cAMP + R2C2 R2 (4cAMP) + 2C

 active C subunit catalyzes the transfer of the

γ phosphate of ATP to a serine or threonine
residue.
Phospodiesterase

 Causes hydrolysis of cAMP to 5’AMP

reduces cAMP levels terminating
the action of hormone
 11 members
 Inhibitors: caffeine, methylated
xanthine derivatives
Cyclic Guanosine
Monophosphate (cGMP)

 Intracellular signal
 Nucleotide formed from Guanosine
Triphosphate (GTP) by guanylyl
cyclase.
Cyclic Guanosine Monophosphate
(cGMP)
Cyclic Guanosine Monophosphate
(cGMP)
Cyclic Guanosine Monophosphate
(cGMP)
Calcium

 intracellular messenger of hormone action

 extracellular Ca2+ = 5mmol/L
 intracellular Ca2+ = 0.05-10μmol/L
* ensure controlled level
* prolonged elevation intracellularly is very
toxic
* Na+ / Ca2+ exchange mechanisms, Ca2+ -
ATPases pump Ca2+
 binds with calmodulin
Calmodulin
 17-kDa protein
 4 Ca2+ binding sites

Ca2+ + Calmodulin activate enzymes & ion

channels, regulates
actin- myosin complex
of smooth muscle, cell
motility, mitosis,
granule release &
endocytosis
Enzymes & Proteins Regulated by
Calcium or Calmodulin

 Adenylyl cyclase
 Ca2+ - dependent protein kinases
 Ca2+ - Mg2+ - ATPase
 Ca2+ - phospholipid-dependent protein kinase
 Cyclic nucleotide phosphodiesterase
 Some cytoskeletal proteins & ion channels
 Nitric oxide synthase, Phosphorylase kinase
 Phosphoprotein phosphatase 2B
 Some receptors (eg NMDA-type glutamate receptor)
Ca2+ + Hormone Receptor EFFECT

Phosphatidylinositol
Metabolism

* Some signal must provide communication

between intracellular Ca2+ reservoirs &
hormone receptor on plasma membrane.
Phosphatidylinositol
metabolism
Sources of phosphatidylinositol:
 ACTH and cAMP in the adrenal cortex

 Angiotensin II

 Potassium

 Serotonin

 Luteneizing Hormone in the ovary

 Luteneizing Hormone & cAMP in the Leydig

cells of the testes
Phosphatidylinositol
metabolism