MEDICAL

1. HORMONES
XIANG ZHUXING

2. Introduction of Hormones
 Most glands of the body deliver their
secretions by means of ducts. These are
called exocrine glands.
 There are few other glands that produce
chemical substance that they directly
secrete into the bloodstream for
transmission to various target tissues.
 These are ductless or endocrine glands.
 The secretions of endocrine glands are
called as hormones.

3. Definition of Hormones
 It is a chemical substance which is produced
in one part of the body, enters the
circulation and is carried to distant target
organs and tissues to modify their
structures and functions.
 Hormones are strictly speaking stimulating
substances and act as body catalysts.

4. Properties of Hormones
 They act as chemical messengers, are required
in small amounts.
 They are secreted in blood prior to their use.
 Site of synthesis and action is different except
autocrines.
 Are not used up in reaction.
 Their activity can be monitored by their blood
levels.
 These can be proteins, amino acids or steroids.

5. Target Cell
 Hormones circulate to all tissues but only
activate cells referred to as target cells.
 Hormone can affect several different cell
types;
 More than one hormone can affect a given cell
type;
 Hormones can exert many different effects in
one cell or in different cells.

6. Hormone Receptors
 Target cells must distinguish hormones (in
small amounts and similar molecules) by
binding receptors
 (1) binding should be specific
 (2) binding should be saturable
 (3) binding should occur within the
concentration range of the expected
biologic response

7. Contd
 Receptors are proteins, two functional
domains:
 (1) A recognition domain binds the hormone
ligand;
 (2) A second region generates a signal that
couples hormone recognition to some
intracellular function.
 Receptors are located on the plasma
membrane and inside the cells (cytoplasm,
nucleus)

8. Contd
Target organs – Tissues with specific receptors
No receptors - Not a target organ

9. Target Cell Activation
 Target cell activation depends on three
factors
 Blood levels of the hormone
 Relative number of receptors on the target cell
 The affinity of those receptors for the
hormone
 Up-regulation：target cells form more
receptors in response to the hormone
 Down-regulation：target cells lose
receptors in response to the hormone

10. classification
self-signaling
adjacent signaling
distant signaling

11. 1. Hypothalamus
2. Pituitary
3. Pineal gland
4. Thymus
5. Thyroid gland
6. Parathyroid glands
7. Langerhans’ islet of
pancreas
8. Adrenal glands
9. Sex glands
The major hormone
secreting glands are:

12. Contd
The major hormone secreting glands are:
Pituitary, hypothalamus, thyroid, adrenal,
pancreas, ovaries and testes.
Thymus, pineal gland and parathyroid gland.
Hormones can be classified according to
chemical composition, solubility, location of
receptors, and the nature of the signal used
to mediate hormonal action within the cell.

13. Classification

15. Ch
catecholamines
polypeptides
or
glycoprotein

16.  Hormones are synthesized & modified for full
activity in a variety of ways.
 Some hormones are synthesized in final form
and secreted immediately.
Included in this class are steroid hormones.
 Some, such as the catecholamines are
synthesized in final form and stored in the
producing cells.
Synthesis of Hormones

17.  While others, like insulin, are synthesized
from precursor molecules in the producing
cell, and then are processed and secreted
upon a physiologic cue (plasma glucose
concentrations).
 Finally, still others are converted to
active forms from precursor molecules in
the peripheral tissues (T3 and DHT).
Contd

18.  Are secreted directly into the blood
 Peptide and protein hormones are secreted
by exocytosis
 Steroid (lipophilic) hormones continuously
penetrate the membrane (they are not
accumulated in cells, their concentration in
blood is determined by the speed of
synthesis)
Fate of Hormones in The Organism

19. Regulation of Hormone Secretion
 Hormones reach target organs, exert their
metabolic effects, also reach their site of
production.
 Here, they can inhibit the production of
hormone. This is called as feedback inhibition.
 Sometimes the concentration of the hormone
is less, which stimulates the production of
hormone by a process of feedback
stimulation.

21. Transport of Hormones in Blood
 Protein and peptide nature – in free state
 Steroid hormones and thyroid hormones –
bound with alpha-globulins or albumins
 Catecholamines – in free state or bound
with albumins, sulphates or glucuronic acid
 Reach the target organs
 Cells have the specific receptors to certain
hormone

22. The Final Effects of Hormones Action
 Change the permeability of cell membrane,
accelerate the penetration of substrates,
enzymes, coenzymes into the cell and out of
cell.
 Acting on the allosteric centers affect the
activity of enzymes (Hormones penetrating
membranes).

23. Contd
 Affect the activity of enzymes through the
second messengers (cAMP). (Hormones that can
not penetrate the membrane).
 Act on the genetic apparatus of the cell
(nucleus, DNA) and promote the synthesis of
proteins (Steroid and thyroid hormones).
 Induce secretory activity and stimulate mitosis

24. Inactivation of hormones
 After biochemical effect hormones are
released and metabolized
 Hormones are inactivated mainly in liver
 Inactive metabolites are excreted mainly
with urine
 Half-life
 from several min to 20 min – for the majority
of hormones
 till 1 h – for steroid hormones
 till 1 week – for thyroid hormones

25. Factors Regulating Hormone
Action
 Action of a hormone at a target organ is
regulated by four factors:
 1. Rate of synthesis and secretion: The hormone
is stored in the endocrine gland.
 2. In some cases, specific transport systems in
plasma.
 3. Hormone-specific receptors in target cell
membranes which differ from tissue to tissue.
 4. Ultimate degradation of the hormone usually
by the liver or kidneys.

27. Mechanisms of Hormone Action
 Two mechanisms, depending on their chemical
nature
1. Water-soluble hormones (all amino acid–
based hormones except thyroid hormone)
 Cannot enter the target cells
 Act on plasma membrane receptors
 Coupled by G proteins to intracellular
second messengers that mediate the
target cell’s response

28. Contd
2. Lipid-soluble hormones (steroid and
thyroid hormones)
 Act on intracellular (cytoplasm or
nucleus) receptors that directly
regulate gene expression.

29. Plasma Membrane Receptors
Structure:usually 3 parts

30. Plasma Membrane Receptors and
Second-Messenger Systems
 Intracellular second messenger is utilized
to implement the hormonal action and
involves:
1. G-protein-coupled adenylate cyclase cAMP
system.
2. G-protein-coupled phosphatidylinositol (PIP2)
Ca2+ pathway.

31. cAMP Signaling Mechanism
Hormone (first messenger) binds to
receptor
Receptor activates G protein
G protein activates adenylate cyclase
Adenylate cyclase converts ATP to cAMP
(second messenger)
cAMP activates protein kinases

32. Activated kinases phosphorylate various
proteins, activating some and inactivating
others
cAMP is rapidly degraded by the enzyme
phosphodiesterase
Intracellular enzymatic cascades have a
huge amplification effect
cAMP Signaling Mechanism

33. Figure 16.2
Hormone (1st messenger)
binds receptor.
Receptor
activates G
protein (GS).
G protein
activates
adenylate
cyclase.
cAMP acti-
vates protein
kinases.
Adenylate
cyclase
converts ATP
to cAMP (2nd
messenger).
Receptor
G protein (GS)
Adenylate cyclase
Triggers responses of
target cell (activates
enzymes, stimulates
cellular secretion,
opens ion channel,
etc.)
Hormones that
act via cAMP
mechanisms:
Epinephrine
ACTH
FSH
LH
Inactive
protein kinase
Extracellular fluid
Cytoplasm
Active
protein
kinase
GDP
Glucagon
PTH
TSH
Calcitonin
1
2 3 4
5

35. Binding of Hormone to Receptor Leads to:
 Conformational change in the receptor and
G-protein (α, β, γ subunits).
 It cleaves the trimeric form into activated
α-GTP complex.
 G-protein is a peripheral protein; which
diffuses along the inner surface of the
plasma membrane to reach the effector
protein.
 Through allosteric modification the message
is conveyed to the effector protein

36. Contd
 Effectors are intracellular enzymes like
adenylate cyclase.
 On activation they produce second
messengers like cAMP.
 cAMP is formed from ATP by adenylate
cyclase action .
 In turn it activates protein kinase A which
phosphorylates intracellular proteins.

37. c AMP binds to (R) of protein kinase A.
Catalytic units (C) are released as active enzyme.

38. Phosphorylation by Protein Kinase A

39. Contd
 GLUCAGON: This leads to inhibition of
glycogen synthase and activation of
glycogen phosphorylase, ultimately resulting
in inhibition of glycogenesis.
 On the other hand the inhibitory system
comprises of receptors (Ri) and inhibitory
regulatory complex (Gi).

44.  Used by some amino acid–based hormones in
some tissues
Involves a G protein
G protein activates phospholipase C (PLC)
phospholipase splits membrane phospholipid
phosphatidylinositol (PIP2) into two second
messengers: diacylglycerol (DAG) and
Inositol- 1, 4, 5, triphosphate(IP3)
PIP2-Ca Signaling Mechanism

45. Contd
 Intracellular IP3 releases Ca2+. A calcium
binding protein, calmodulin binds Ca2+.The
complex activates a number of intracellular
enzymes. (Eg.Ca2+-calmodulin complex inhibits
glycogenesis, stimulates glycogenolysis.)
 DAG activates protein kinase C which in turn
phosphorylates specific enzymes and other
proteins in the cytosol to modulate their
activities.

47. Second Messengers
 Second messengers: Ca2+, DAG are
identified for GnRH, TRH, Acetyl choline,
Angiotensin-II, Vasopressin, Oxytocin
 The second messengers of Insulin, GH,
Prolactin are a kinase or phosphatase
cascade.
 Hormone itself is first messenger.
 The message is communicated to the cell Via.
second messengers

48. Intracellular Receptors and
Direct Gene Activation
 Steroid hormones and thyroid hormones
1. Diffuse into their target cells and bind with
intracellular receptors
2. Receptor-hormone complex enters the
nucleus
3. Receptor-hormone complex binds to a
specific region of DNA
4. This prompts DNA transcription to produce
mRNA
5. The mRNA directs protein synthesis

49. Figure 16.3
mRNA
New protein
DNA
Hormone
response
elements
Receptor-
hormone
complex
Receptor
protein
Cytoplasm
Nucleus
Extracellular fluid
Steroid
hormone
The steroid hormone
diffuses through the plasma
membrane and binds an
intracellular receptor.
The receptor-
hormone complex enters
the nucleus.
The receptor- hormone
complex binds a hormone
response element (a
specific DNA sequence).
Binding regulates
transcription of the
gene to mRNA.
The mRNA directs
protein synthesis.
Plasma
membrane
1
2
3
4
5

51. Contd
 Cytosolic receptors found for the following
steroid hormones:
 a. Glucocorticoids.
 b. Mineralocorticoids
 c. Progestins.
 d. Estrogens.
 e. Calcitriol.
 Nuclear receptors are identified for
Thyroxine, Triiodothyronine.

53. Major Differences B/W Hormones
and Enzymes
Parameters Hormones Enzymes
Chemical nature May be Protein, Amino acid or
Steroids
Always Proteins except
Ribozyme
Delivery to blood circulation Delivered first to the circulation
prior to use
Not so
Site of synthesis and action Is Different Is the Same
Role
As chemical messenger B/W the
cells /tissues or organs
As catalyst to enhance rate of
reaction
Regulation Negative feedback mechanism
and CNS
Factors: pH; temperature;
conc. of enzyme and substrate
and inhibitors
Primary action Is on the target tissues through
receptors to express instructions
Is on the specific substrates for
catalysis

55. References
 Bain DL, Heneghan AF, Connaghan-Jones KD, et al: Nuclear receptor
structure: implications for function. Ann Rev Physiol 2007;69:201.
 Bartalina L: Thyroid hormone-binding proteins: update 1994.Endocr Rev
1994;13:140
 Cristina Casals-Casas C, Desvergne B: Endocrine disruptors:from
endocrine to metabolic disruption. Annu Rev Physiol 2011;73:23.135–162.
 Taguchi A, White M: Insulin-like signaling, nutrient homeostasis, and
life span. Ann Rev Physiol 2008;70:191.
 Lippincott’s’’ Illustrated Reviews Biochemistry
 Harper's Illustrated Biochemistry
 Path physiology of Endocrinology system Colorado State University
 Basic and Clinical Endocrinology – Francis Greenspan – David
G.Gardner
 Text book of Medical biochemistry – MN Chatterjea