Introduction to

Endocrinology
Coordination of Body Functions

1) nervous system (neurotransmitters into the

synaptic junctions – locally)
2) endocrine system (hormones into blood)
3) neuroendocrine (neurohormones into blood)
4) paracrines (secreted into extracellular fluid
and affect neighboring different target cells)
5) autocrines (affect same cells)
6) cytokines (peptides - 5,4 or 2 - interleukins,
lymphokines, adipokines (leptin))
 some endocrine hormones affect many
different types of cells of the body (growth
hormone, thyroxine)
 other hormones affect mainly specific
target tissues (ACTH – adrenal cortex)
 regulation: metabolism, growth and
development, water and electrolyte balance,
reproduction, and behavior
Chemical Structure and Synthesis

1) proteins and polypeptides

2) steroids
3) derivatives of the amino acid tyrosine
(thyroid and the adrenal medullae)
 there are no known polysaccharides or
nucleic acid hormones
1) Protein Hormones

 widespread, water soluble

 from 3 (TRH) to 200 amino acids (growth
hormone and prolactin)
 more than100 amino acids – proteins
 synthesized on the rough end of the ER
 preprohormones – prohormones (ER) –
hormones (Golgi apparatus & secretory
vesicles) – exocytosis (Ca, cAMP)
2) Steroid Hormones

 usually synthesized from cholesterol

 are not stored
 lipid soluble
 most of cholesterol comes from plasma, but
there is also de novo synthesis
 consist of three cyclohexyl rings and one
cyclopentyl ring combined into a single
structure
3) Amine Hormones

 derived from tyrosine

 most of the thyroid hormones combine with
plasma proteins
 4x more epinephrine than norepinephrine
 taken up into preformed vesicles and stored
until secreted (exocytosis)
 in the plasma in free form or in conjugation
with other substances
Hormone Secretion

 some hormones (epinephrine) are secreted

within seconds after stimulation, and
develop action within seconds to minutes
 thyroxine or growth hormone may require
months for full effect
 concentrations of hormones are incredibly
small (from 10-12 to 10-6g/ml) – rates of
secretion are extremely small (μg-mg/day)
Control of Hormone Secretion

 in most instances – negative feedback

mechanisms
 controlled variable is sometimes not the
secretory rate of the hormone itself but the
degree of activity of the target tissue
 regulation of gene transcription and
translation steps involved in the synthesis of
hormones and steps involved in processing
hormones or releasing stored hormones
 positive feedback – LH, oxytocin
 cyclical variations – seasonal changes,
various stages of development and aging, the
diurnal (daily) cycle, and sleep
Transport of Hormones in Blood

 water-soluble hormones (peptides and

catecholamines) – dissolved in the plasma
 steroid and thyroid hormones – circulate in
the blood mainly bound to plasma proteins
(usually less than 10% free in solution),
biologically inactive (serve as reservoirs,
greatly slows their clearance from the
plasma)
Clearance of Hormones from Blood

 concentration of a hormone in the blood :

1) rate of hormone secretion into the blood
2) rate of removal of the hormone from the
blood (metabolic clearance rate –
number of milliliters of plasma cleared
of the hormone per minute)
 one measures : the rate of disappearance of
hormone from the plasma & concentration
1) metabolic destruction by the tissues
2) binding with the tissues
3) excretion by the liver into the bile
4) excretion by the kidneys into the urine
 liver damage  excessively high
concentration of steroid hormones
 half-life of angiotensin II < 1 minute,
thyroid hormones 1-6 days
Hormone Receptors and Their
Activation
 binding to specific receptors at the target
cell – first step of a hormone's action
 initiation of a cascade of reactions in the
cell – amplification of the effect
 hormonal receptors are large proteins , each
cell usually has some 2000 to 100,000
receptors
 receptor is highly specific for a single
hormone
1) in or on the surface of the cell membrane
(protein, and catecholamine hormones )
2) in the cell cytoplasm (steroid hormones)
3) in the cell nucleus (thyroid hormones)
 number of receptors usually does not
remain constant (increase or decrease)
Intracellular Signaling

 formation a hormone-receptor complex

– alteration of function of receptor :

1) ion channel-linked receptors

2) G protein-linked hormone receptors
3) enzyme-linked hormone receptors
4) intracellular hormone receptors and activation of genes
1) Ion Channel-Linked Receptors

 acetylcholine & norepinephrine

 change in the structure of the receptor
 opening or closing a channel for one or
more ions (Na, K, Ca)
 few directly, most indirectly by coupling
with G protein-linked or enzyme-linked
receptors
2) G Protein-Linked Hormone Receptors

 heterotrimeric GTP-binding proteins

 > 1000 known G protein-coupled receptors
 all have 7 transmembrane segments that
loop in and out of the cell membrane
 cytoplasmic tail is coupled to G protein
(include three parts – α, β, and γ subunits)
 binding of hormone – conformational
change in receptor – activation of G protein
 activated G proteins
1) open or close cell membrane ion channels
2) change the activity of an enzyme in the cytoplasm
 G proteins binds GDP (α subunit)
 displacement of GDP by GTP causes the α
subunit to dissociate from the trimeric
complex and to associate with other
intracellular signaling proteins
 inhibitory (Gi) & stimulatory (Gs) proteins
3) Enzyme-Linked Hormone Receptors

 some receptors, when activated, function

directly as enzymes or are closely
associated with enzymes that they activate
 pass through the membrane only once
 hormone-binding site on the outside of the
cell membrane
 catalytic or enzyme-binding site on the
inside
 leptin receptor
 member of a large family of cytokine receptors that do
not themselves contain enzymatic activity but signal
through associated enzymes
 one of the signaling pathways occurs through a
tyrosine kinase of the janus kinase (JAK) family,
JAK2
4) Intracellular Hormone Receptors and
Activation of Genes

 steroid hormones, thyroid hormones,

retinoid hormones, and vitamin D
 receptors in the cytoplasm or nucleus
 binding with a specific regulatory
(promoter) sequence of the DNA –
hormone response element
 transcription of specific genes and
formation of mRNA
Second Messenger Mechanisms

 cAMP, cGMP
 calcium ions and associated calmodulin
 4 binding sites for Ca, 3 or 4 changes its shape
 activation/inactivation of protein kinases
 phosphorylation of proteins (myosin light
chain kinase – smooth muscle contraction)
 products of membrane phospholipid
breakdown
could be
Gi

amplification
of the effect –
cascade of
reactions
phosphatidylinositol
biphosphate

contraction,
secretion
Steroid Hormones Increase
Protein Synthesis
 these proteins then function as enzymes,
transport proteins, or structural proteins
 aldosterone – for 45 minutes, protein which
promote sodium reabsorption and
potassium secretion
 full action is delayed for at least 45
minutes-up to several hours or even day
Thyroid Hormones Increase Gene
Transcription in the Cell Nucleus
 thyroxine and triiodothyronine
 bind directly with receptor proteins in the
nucleus (activated transcription factors
located within the chromosomal complex )
 they control the function of the gene
promoters
 formation of many types of intracellular
proteins
 thyroid hormones can continue to express
their control functions for days or even
weeks
Measurement of Hormone
Concentrations in the Blood
 extremely minute quantities (pg/mL)
 radioimmunoassay
 production of antibody that is highly specific
for the hormone to be measured is produced
 small quantity of this antibody (smaller than
total possible) is mixed with:
1) sample containing the hormone to be measured
2) appropriate amount of purified standard hormone
that has been tagged with a radioactive isotope
 error of 10 to 15 percent
Measurement of Hormone
Concentrations in the Blood
 ELISA (enzyme-linked immunosorbent
assay)
1) it does not employ radioactive isotopes
2) much of the assay can be automated using 96-well
plates
3) cost-effective and accurate method for assessing
hormone levels