Degree in Biomedical Sciences
General Biochemistry
Hormones
2
Hormones
• A specific chemical compound
• Produced by a specific tissue of the body
• Where it is released in the body fluids
• And carried to a distant target tissue
• Where it affects a pre-existing mechanism
• And is effective in small amounts
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Long Distance Communication: Hormones
• Signal Chemicals
• Made in endocrine
cells
• Transported via
blood
• Receptors on target
cells
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Long Distance Communication: Hormones
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Paracrines and Autocrines
• Local communication
• Signal chemicals diffuse to
target
• Example: Cytokines
• Autocrine–receptor on
same cell
• Paracrine–neighboring
cells
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Modes of Endocrine Related Control
• Autocrine signalling – chemical message affects
the cell that secrets it
• Paracrine signalling – chemical message affects
neighboring cell
• Endocrine signalling – chemical message
(hormone) secreted into the blood and acts on
distant target organ
• Neuroendocrine signalling – hormone secreted by
neuron
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Hormone Classification
1. Proteins and polypeptides
• Large proteins
• Small peptides
• Glycoproteins
2. Lipids (steroids)
• Cholesterol derivatives
• Eicosanoids (fatty acid derivatives)
3. Amines (amino acid derivatives )
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Hormone Classification
• Protein hormones
• Unable to pass through the plasma
membrane because of size and charge
• Receptors must be located on the plasma
membrane
• Extracellular domain for interaction with
hormone
• Intracellular signalling system
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Hormone Classification
• Protein hormones (contd)
• Range from 3 amino acids to hundreds of
amino acids in size
• Often produced as larger molecular weight
precursors that are proteolytically cleaved to
the active form of the hormone
• Protein/peptide hormones are water soluble
• Comprise the largest number of hormones,
perhaps in thousands
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Hormone Classification
• Protein hormones (contd)
• Examples
• ACTH, GH, TSH, PRL, LH,
Oxytocin, Vasopressin, PTH,
Insulin, Glucagon
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Hormone Classification
Amine Hormones
• Derived from the
amino acid tyrosine
• Small size
• OH group
• Benzine ring
• Stored until secreted
• Examples
• Triiodothyronine (T3)
• Thyroxine (T4)
• Epinephrine
• Norepinephrine
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Hormone Classification
• Steroid Hormones
• Precursor: Cholesterol
• Lipophilic
• They are immediately released from the
cell following synthesis
• There are cytoplasmic or nuclear
receptors on target cells
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Hormone Classification
• Steroid Hormones (contd)
• Activate DNA for protein synthesis
• Slower acting, longer half-life
• Examples
• Androgens, Estrogens, Progesterone,
Glucocorticoids, Mineralocorticoids
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Membrane Receptor Classes
• G-protein-coupled
• Ligand-gated channel
• Receptor enzymes
• Integrin
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G-Protein Coupled Receptor
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Receptor Locations
• Cytosolic or Nuclear
• Lipophilic ligand
enters cell
• Often activates genes
• Slower response
• Cell membrane
• Lipophobic ligand
can't enter cell
• Hence they have
outer surface receptor
• Fast response
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Cellular Mechanism of Hormone Action
• Hormone receptors
• Located in or on the plasma membrane or in the
intracellular compartment of the target cell
• Water-soluble hormones
• High molecular weight
• Cannot diffuse across the plasma membrane
• Lipid-soluble hormones
• Easily diffuse across the plasma membrane and
bind to cytosolic or nuclear receptors
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Cellular Mechanism of Hormone Action
• Water-soluble hormones
• Act as first messenger
• They initiate signal transduction which
involves a seconds messenger in a cascade
fashion
• Second messenger molecules
• Calcium
• Cyclic adenosine monophosphate (cAMP)
• Cyclic guanosine monophosphate (cGMP)
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Cellular Mechanism of Hormone Action
• Lipid soluble hormones
• Steroid hormones
• Androgens, estrogens, progestins, glucocorticoids,
and mineralocorticoids hormones
• Diffuse across the plasma membrane
• Bind to cytoplasmic or nuclear receptors
• Activate
• DNA polymerase
• RNA transcription and translation
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Mechanism of Lipid Soluble Hormones Action
1. A lipid soluble
hormone diffuses
from the blood,
through the
intestitial fluid into
the cell
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Mechanism of Lipid Soluble Hormones Action
2. The hormone will
bind to a receptor
and activate it
3. The receptor may
be in the
cytoplasm or the
nucleus
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Mechanism of Lipid Soluble Hormones Action
4. An activated
receptor then
alters gene
expression, by
either turning
on or off
transcription of
a specific gene
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Mechanism of Lipid Soluble Hormones Action
5.
If the gene is
turned off the
protein for
which it codes
is not
produced and
some process
do not occur
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Mechanism of Lipid Soluble Hormones Action
6. If a new gene
is turned on,
a new protein
is produced
by protein
synthesis
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Mechanism of Lipid Soluble Hormones Action
7.
The new protein
alters the cell’s
activity and
causes the typical
physiological
response of that
hormone
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Mechanism of Water Soluble Hormones Action
1. A water soluble
hormone diffuses
from the blood,
and binds to its
receptor in the
plasma
membrane of the
target cell
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Mechanism of Water Soluble Hormones Action
2. The binding
activates the
G-protein
which acts to
turn on
adenylate
cyclase
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Mechanism of Water Soluble Hormones Action
3. Adenylate
cyclase
converts ATP
into cyclic
AMP in the
cytoplasm of
the cell
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Mechanism of Water Soluble Hormones Action
4. Cyclic AMP
activates one or
several protein
kinases, which
may be free in the
cytoplasm or
bound to the cell
membrane
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Mechanism of Water Soluble Hormones Action
5. Activated
protein
kinases
phosphorylate
one or several
enzymes
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Mechanism of Water Soluble Hormones Action
6. This causes
some enzymes
to become
active and
others to
inactivate
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Mechanism of Water Soluble Hormones Action
7. Enzymes activated
by phosphorylation
catalyse reactions
that produce
physiological
responses
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Mechanism of Water Soluble Hormones Action
8. Furthermore,
phosphorylation
by a protein
kinase can inhibit
certain enzyme,
so that, some
reaction no longer
occur
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Mechanism of Water Soluble Hormones Action
9. After a brief
period of time, an
enzyme called
phosphodiesterase
inactivates cAMP
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Control of Endocrine Activity
• The physiological effects of hormones
depend largely on their concentration in
blood and extracellular fluid
• Almost inevitably, disease results when
hormone concentrations are either too high
or too low
• Therefore, precise control over circulating
concentrations of hormones is crucial
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Control of Endocrine Activity
• The concentration of hormones as
seen by target cells is determined by
three factors
• Rate of production
• Rate of delivery
• Rate of degradation and elimination
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Control of Endocrine Activity
• Rate of production
• Synthesis and secretion of hormones
are the most highly regulated aspect of
endocrine control
• Such control is mediated by positive
and negative feedback circuits
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Control of Endocrine Activity
• Rate of delivery
• An example of this effect is blood
flow to a target organ or group of
target cells
• High blood flow delivers more
hormone than low blood flow
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Control of Endocrine Activity
• Rate of degradation and elimination
• Hormones, like all biomolecules,
have characteristic rates of decay, and
are metabolised and excreted from the
body through several routes
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The Hypothalamus
• Integrates functions that maintain chemical
and temperature homeostasis
• Controls the release of hormones from the
anterior and posterior pituitary
• Secretes substances that control the anterior
pituitary gland
• Releasing factors
• Inhibiting factors
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Hypophysiotopic hormones
• Hypophysiotopic hormones is a hormone
secreted by the hypothalamus that
stimulates or inhibits the
adenohypophysis portion of the pituitary
gland
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Hypophysiotopic Hormones
• Corticotropic Releasing Hormone
(CRH)
• Released from the hypothalamus
• It interacts with the pituitary to produce
adrenocorticotropin hormones (ACTH)
• Involved in the stress response
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Hypophysiotopic Hormones
• Growth Hormone Releasing
Hormone (GHRH)
• The hormone released from the
hypothalamus
• Causes the release of growth
hormone from the pituitary gland
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Hypophysiotopic Hormones
• Growth Hormone Inhibitory Hormone
(GHIH)
• Also known as somatostatin
• Delta cells of the pancreas, the stomach, and
intestines also secrete it
• Inhibits the release of GH and TSH
• Suppresses the release of gastrointestinal and
pancreatic hormones (glucagon and insulin)
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Hypophysiotopic Hormones
• Prolactin Releasing Hormone
(PRH)
• Originates in the hypothalamus
• Stimulates the secretion of
prolactin in the pituitary gland
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Hypophysiotopic Hormones
• Gonadotropin Releasing Hormone (GnRH)
• Hormone made by the hypothalamus
• GnRH causes the pituitary gland to make
luteinising hormone (LH) and
follicle stimulating hormone (FSH)
• These hormones are involved in
reproduction
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Hypophysiotopic Hormones
• Thyrotrophic Releasing (TRH)
Hormone
• Hormone released by the hypothalamus
• Controls the release of thyroid stimulating
hormone from the anterior pituitary
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Pituitary Gland
• Connected to the hypothalamus
• Master gland of the endocrine
system
• Pituitary sits in a bone cavity called
the sella turcica or “turkish saddle”
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Pituitary Gland
• The Pituitary Gland is divided
into 2 areas which differ;
• Structurally and functionally
• Each area has separate types of
hormone production
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Structure of the Pituitary Gland
• Two distinct lobes
• Anterior pituitary
• (adenohypophysis; pars distalis)
• True endocrine tissue
• Secretes classic hormones
• Posterior pituitary
• (neurohypophysis; pars nervosa)
• Neural tissue
• Secretes neurohormones
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The Hypothalamic-Hypophyseal Portal System
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Anterior Pituitary
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Anterior Pituitary Hormones
• Thyroid stimulating hormone (TSH)
• Target – thyroid gland
• Effect – triggers the release of thyroid
hormones
• Adrenocorticotropic hormone (ACTH)
• Target – adrenal cortex
• Effect – cells that produce steroid hormones
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Anterior Pituitary Hormones
• Luteinising hormone (LH)
• Glycoprotein
• Targets – follicle cells (females),
interstitial cells of testes (males)
• Effects – ovulation, formation of corpus
luteum, secretion of progesterone
(females), secretion of testosterone (males)
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Anterior Pituitary Hormones
• Follicle stimulating hormone (FSH)
• Glycoprotein
• Stimulates gametes
• Effects – follicle development and
estrogen secretion(females), sperm
maturation (males)
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Anterior Pituitary Hormones
• Prolactin
• Target - breast
• Effect - breast development and milk
production and involved in testicular function in
males
• Growth hormone
• Target – all cells
• Effect – stimulates growth in general and the
skeletal system in particular
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Posterior Pituitary
• Antidiuretic Hormone (ADH)
• Made in hypothalamus, secreted in posterior pituitary
• Target – kidneys
• Effect
• Reabsorption of water (conserves water in the
body)
• Reduces urine volume
• Dehydration of body stimulates osmoreceptors
• High blood volume → less ADH and loss of water
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Posterior Pituitary
• Oxytocin
• Synthesised in the cell bodies of
hypothalamic neurons
• Targets – reproductive organs
• Effects – contraction of smooth muscles
(labour contractions, milk
ejection; ductus deferens, prostate
gland – ejaculations)
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Synthesis, storage, and release of posterior pituitary hormones
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Thyroid Gland
•
•
•
•
Butterfly shaped
Two lobes connected by an isthmus
Straddles the trachea
Largest endocrine gland
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The Thyroid Gland
Trachea
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Thyroid Gland
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The Thyroid Hormones
• Thyroxine (T4)
• Triiodothyronine (T3)
• Thyroid-Stimulating Hormone (TSH)
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The Two Principal Thyroid Hormones
1.
2.
Thyroxine (T4 )
Triiodothyronine (T3)
• They are required for homeostasis of all cells
• They influence cell differentiation, growth,
and metabolism
• They are considered the major metabolic
hormones because they target virtually every
tissue
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Thyroid Hormone Biosynthesis
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Thyroid Hormone Biosynthesis
• Thyroid hormone synthesis includes
the following steps:
1. Iodide (I-) trapping by the thyroid
follicular cells
2. Diffusion of iodide to the apex of the
cells
3. Transport of iodide into the colloid
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Thyroid Hormone Biosynthesis
3. Oxidation of inorganic iodide to iodine and
incorporation of iodine into tyrosine residues
within thyroglobulin molecules in the colloid
4. Combination of two diiodotyrosine (DIT)
molecules to form tetraiodothyronine
(thyroxine, T4) or of monoiodotyrosine
(MIT) with DIT to form triiodothyronine (T3)
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Thyroid hormone biosynthesis
5. Uptake of thyroglobulin from the colloid into
the follicular cell by endocytosis, fusion of the
thyroglobulin with a lysosome, and proteolysis
and release of T4, T3, DIT, and MIT
6. Release of T4 and T3 into the circulation
7. Deiodination of DIT and MIT to yield tyrosine
• T3 is also formed from monodeiodination of T4 in
the thyroid and in peripheral tissues
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Secretion of thyroid hormones
• Endocytosis of iodinated thyroglogulin
from lumen into the cell
• There is fusion of endocytic vesicles with
primary lysosomes
• Degradation of thyroglobulin in secondary
lysosomes and liberating T3 and T4 into the
circulation out of cell
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Secretion of thyroid hormones
• 70% of iodine bound by throglobulin is in
the form MIT and DIT
• After liberation from thyroglobulin these
compounds are deiodinated by enzyme
deionidase and tyrosine and iodide is
returned to further utilisation
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Transport of thyroid hormones by blood
• Thyroid hormones are not very soluble in water (but are
lipid soluble)
• Thus, they are found in the circulation associated with
binding proteins:
• Thyroid Hormone-Binding Globulin (~70% of hormone)
• Pre-albumin (transthyretin), (~15%)
• Albumin (~15%)
• Less than 1% of thyroid hormone is found free in the
circulation
• Only free and albumin bound thyroid hormone is
biologically available to tissues
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Feedback mechanism
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Feedback Mechanism
• The hypothalamus releases TRH, which acts
on the anterior pituitary gland, TSH, or
thyrotropin, a glycoprotein that binds to
TSH receptors on the thyroid gland
• This binding initiates thyroid activity,
resulting both in hypertrophy and
hyperplasia, as well as the production of
thyroid hormones
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Functions of thyroid hormones
• Stimulate metabolic rate
• Increasing number and size of mitochondria
• Increasing enzymes in the metabolic chain
• Resting metabolic rate may increase 100%
with excess thyroid hormones or decrease by
50% with a deficiency
• Important in growth and development
particularly skeleton and nervous system
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Effects of thyroid hormones
• Foetal brain and skeletal maturation
• Increase in basal metabolic rate
• Inotropic and chronotropic effects on heart (increase
contractility)
• Stimulates gut motility
• Increase bone turnover
• Increase in serum glucose, decrease in serum
cholesterol
• Play role in thermal regulation
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Iodinisation of Salt
1. Salt is universally and regularly
consumed
2. It is inexpensive
3. The technology to iodinise salt is
simple
4. There are many studies that support
the effectiveness of iodinising salt
80
Parathyroid Gland
• Four small glands located on the dorsal side of
the thyroid gland
• Produces parathyroid hormone
• Responsible for monitoring plasma Ca2+
• Parathyroid Hormone (PTH) raises the level of
calcium in the blood, decreases levels of blood
phosphate
• Partially antagonistic to calcitonin of thyroid
gland
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Actions of PTH
• Increase [Ca2+], decrease [PO42-]
• In bone
• Osteoclastic reabsorption releases Ca2+ and
PO42-
• In kidney
• Increased PO42- excretion
• Increased Ca2+ reabsorption
• Increased hydroxylation of vitamin D
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Functions of Vitamin D
• Calcitriol - 1,25 dihydroxy vitamin D3
(1,25(OH)2D3 is the active form of vitamin D
• It stimulates absorption of Ca2+ from the
intestines
• In the kidney it decreases Ca2+ excretion
• In the bone it increases bone mineralisation
• In the small bowel it increases Ca2+ and PO42absorption
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Calcitonin
• Calcitonin is made by the parafollicular C
cells of the thyroid gland
• A large peptide "prohormone" is made and
then cut down to the 32 amino acids
calcitonin
• Causes removal of Ca2+ from plasma to
calcify new bone
• Lowers plasma Ca2+ (opposes PTH)
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Calcitonin
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Parathyroid Function Testing
• Serum calcium and phosphorus
• Urine calcium
• Serum alkaline phosphate
• When ↑Ca, ↓Phosphorus
• ↑Alk Phos in liver disease
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The Adrenal Glands
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Adrenal Gland
Catacholamines
(Epinephrine,
Norepinephrine)
Glucocorticoids
Mineralocorticoids
Weak androgens
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The Adrenal Glands
• The adrenal glands lie just above the kidneys
• Divided into two main sub-organs
• Adrenal cortex
• Secretes the steroid hormones
• Glucocorticoids
• Mineralocorticoids
• Androgens
• Adrenal medulla
• Secretes catecholamines
• Adrenaline (epinephrine)
• Noradrenaline (norepinephrine)
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Zona Reticularis
• Innermost zone – between the fasciculata and
medulla
• Primary secretion is androgens
• Contribute to normal maturation
• Dehydroepiandrosterone (DHEA)
• Androgenic hormones exhibit approximately
the same effects as the male sex hormone –
testosterone
91
Zona Fasciculata
• Middle zone – between the glomerulosa and
reticularis
• Primary secretion is glucocorticoids
• Glucocorticoids are involved in increasing of blood
glucose levels
• However, they have additional effects in protein and
fat metabolism
• The naturally synthesised glucocorticoid of most
importance is cortisol
92
Zona Fasciculata 2
• Glucocorticoids
• Secreted by Zona Fasciculata of the Adrenal
Cortex
• Not stored – Rate of synthesis equals rate of
release
• Synthesised rhythmically
• Controlled by irregular pulses of ACTH
• Major pulses early in morning and after meals
• Influenced by light
93
Zona Glomerulosa
• Outermost zone – just below the adrenal
capsule
• Secretes mineralocorticoids
• Mineralocorticoids are involved in
regulation of electrolytes in ECF
• The naturally synthesised mineralocorticoid
of most importance is aldosterone
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Hormones of the Adrenal Medulla
• Adrenaline (epinephrine)
• Noradrenaline (norepinephrine)
• 80% of released catecholamines are
epinephrine
• Hormones are secreted and stored in the
adrenal medulla and released in
response to appropriate stimuli
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Catecholamines
• Molecules with a
catechol nucleus
and an ethylamine
group
attached in
position 1
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Synthesis of the Catecholamines from Tyrosine
(Dihydroxyphenylalanine)
97
Synthesis of the Catecholamines
1. Tyrosine hydroxylase requires tetrahydrobiopterin
as cofactor
2. The hydroxylation reaction generates DOPA (3,4dihydrophenylalanine)
3. DOPA decarboxylase converts DOPA to dopamine
4. Dopamine β-hydroxylase converts dopamine to
norepinephrine
5. Phenylethanolamine N-methyltransferase converts
norepinephrine to epinephrine
98
Metabolic Actions of Epinephrine
• A central role of epinephrine is to increase the
availability of metabolites for the intensive physical
activity involved in the acute stress situation
• Ways in which the release of glucose from the liver to the
blood is increased by epinephrine
• Breakdown of glycogen stores
• Inhibition of glycogen synthesis
• Stimulation of gluconeogenesis
• Mobilisation of free fatty acids
• Increased metabolic rate
• O2 consumption increases
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