General Pathophysiology of
Endocrine System
March 28, 2017
Interactive homeostatic system: communication between body and
brain by means of neurons and factors circulating in blood
Bienertová-Vašků J, Zlámal F, Nečesánek I, Konečný D, Vasku A.
PLoS One. 2016 Jan 15;11(1)
Regulace
energetické
homeostázy
MCH=melanin concentrating hormon
Effects of hormones
 Pleoitrophism:
 one hormon has more effects in
different tissue
 more hormones modulate one function
Effects of hormones
 Acute - posttranslational effects
 Chronicgenomic effects-trophic
(cell growth and division)
Receptor regulation types:
 up-regulation (genomic effect)
 down-regulation (membrane effect)
Hormone action and receptors
 Hormones act by binding to specific receptors
in the target cell, which may be at the cell
surface and/or within the cell.
 Most hormone receptors are proteins with
complex tertiary structures, parts of which
complement the tertiary structure of the
hormone to allow highly specific interactions,
while other parts are responsible for the effects
of the activated receptor within the cell.
 Many hormones bind to specific cell-surface
receptors where they trigger internal
messengers, while others bind to nuclear
receptors which interact directly with DNA.
Hormone action and receptors
.
 Cell-surface receptors usually
contain hydrophobic sections which
span the lipid-rich plasma
membrane, while nuclear receptors
contain characteristic amino-acid
sequences to bind nuclear DNA (e.g.
so-called 'zinc fingers') as in the
glucocorticoid receptor.
Hormone classes according to the structure
Amines and
amino acids
Peptides,
polypeptides and
proteins
Steroids
Adrenaline
Noradrenaline
Dopamine
Thyreoid
hormones
ACTH,
angiotensine
calcitonine
erythropoietine
FSH
gastrine
glucagone
STH
insulin
LH, Oxytocin
PTH, prolactine
secretine, TSH,
ADH
Aldosterone
Glucokortikoids
Estrogenes
Progesterone
Testosterone
Hormonal activity
 At the molecular level there is little difference in the
way cellular activity is regulated between classical
neurotransmitters that act across synaptic clefts,
intercellular factors acting across gap junctions,
classic endocrine and paracrine activity and a
variety of other chemical messengers involved in
cell regulation - such as cytokines, growth factors
and interleukins; progress in basic cell biology has
revealed the biochemical similarities in the
messengers, receptors and intracellular postreceptor
mechanisms underlying all these aspects
of cell function.
Output of the cell
 Acute - monotrophic
 Chronic-pleiotrophic
 Responsive cell- the cell able to realize
postreceptively adequate response
 Receptive cell- the cell appointed by
receptors
Manner of hormone secretion
 Endocrine secretion – directly to the
blood or indirectly through extracellular
water compartment
 Paracrine secretion – the hormone has
not must not be secreted to the blood
(growth factors, neuroparakrinia)
 Autocrine secretion - f.i. presynaptic
neuromodulation of NE release
Interaction hormone-receptor
Hormone A Hormone B Hormone C
+++ - +
Recognition
+++ - +
Signal forming in cytoplasm or in nucleus
+++ - +
Efector machinery : enzymes, genes et al.
Strong efekt A No effect B No effect C
No effect A Poor effect A
Interaction hormone-receptor
Interactions fixed
with messenger
Mobile interactions
hormone-receptor-
nucleus
Glucagone
Insulin
Noradrenaline
PTH
TSH
ACTH
FSH
LH
ADH
Secretine
Estrogenes
Testosterone
Progesterone
Adrenal cortical
hormones
Thyreoid hormons
Hormone binding globulins
 with small affinity and specifity for the hormone
 albumine, orozomukoid, 1- acid glycoprotein
 with high affinity and higher specifity for the hormone
 TBG, Transkortine (CBG), SHBG
 binding proteins:
 Dysproteinemia acute and chronic
 binding proteins
 Liver cirrhosis
Feedback control
Hormone-hormone
Substrat-hormone
Neuronal control Chronotrophic control
Adrenergic Oscillated
Cholinergic Pulzatile
Dopaminergic Diurnal rhythm
Serotoninergic Sleep-wake rhythm
Endorfinergic Menstrual rhythm
-enkefalinergic Sesonal rhythm
Gabaergic Development rhythm
Koncepce multireceptivní buňky
Signální transdukce
Signální transdukce
Signální transdukce
Signální transdukce
Účinek hormonů
nebílkovinné povahy
na transkripci genů
4 třídy DNA-vazných proteinů
Schema of human circadian system. RHT, retinohypothalamic tract;
SCN, suprachiasmatic nucleus; PVN, paraventricular nucleus
Clin Invest. 2011 Jun;121(6):2133-41. Circadian rhythms, sleep, and metabolism.
Huang W1, Ramsey KM, Marcheva B, Bass J.
ANS-autonomic nerve system
BMR-basal metabolic rate
Nat Rev Neurosci. 2012
Mar 7; 13(5): 325–335
Circadian rhythmicity
 Central clocks - n. suprachiasmaticus
(SCN- anterior hypothalamus). SCN
neurons generate rhythmicity, electric
activity and produce synchronizing
signals.
 These signals control phase of
peripheral clocks oscillations (liver,
muscles, kidneys, heart)
Circadian rhythmicity
 Rhythmic activity of central clocks
synchronized by external light (trc.
retinohypothalamicus)
 Peripheral tissues produce rhythmic
physiological outputs which optimize
action of the body in interaction with
environmental conditions during day
and/ or night time.

Circadian disruption affects multiple organ systems. The diagram
provides examples of how circadian disruption negatively impacts the
brain and the digestive, cardiovascular, and reproductive systems.
Though the diagram displays unidirectional affects, there are various
feedback loops that exist within the system and interactions that occur
between these systems.
Circadian rhythmicity
Circadian oscillations are leaing to
modification of gene expression and
production of proteins.
Nat Rev Neurosci. 2012 Mar 7; 13(5):
325–335
Circadian rhythmicity
 Circadian system function decreases
during aging.
 Earlier phases and lower amplitude of
temperature and some hormone
expressions can be observed
(melatonin, cortisol).
Nuclear and non nuclear actions
of glucocorticoids
Erin L. Zelinski, Scott H. Deibel, Robert J. McDonald
Neuroscience and Biobehavioral Reviews 40 (2014) 80–101
Night time work
 Exposition to light during night time is
leading to disturbances in serotonin
production in SCN.
 This is leading to influencing of cognition
functions, metabolic functions and
peripheral circadian oscillators.
 Light during night time is influencing
secretion of melatonin as well as
melatonin receptor density.

 Increased BMI leads to alteration of
leptin/ghrelin signalling (worse
homeostasis of energy state of the
body)
 Higher risk of obesity, DM II and
cardiovascular diseases
Shift work
Night time work (shift work)
 Lower efficacy of melatonin as antioxidant.
 Premature aging, cardiovascular diseases,
malignancy.
 Eating during night time work period with
higher preference of food with high sugars
and lipids content.
 Metabolism of sugars and lipids does not work
optimally during night time period; higher risk
of obesity and insulin resistance.
Jet lag
 Upon arrival at his destination, the jet traveler who has
crossed multiple time zones experiences a mismatch
between his/her endogenous bodily rhythms and the
new light/dark cycle that is being imposed. This
environmental change produces a variable response in
the body's circadian rhythms, each having different time
requirements for establishing their normal phase
relationships not only with other internal rhythms but with
the environmental cycle as well. It is during this
adjustment period that jet lag symptoms are most severe,
although their severity varies widely among individuals.
Jet lag
 Eastbound travel causes a phase advance in all
body's circadian rhythms while westward flight
has the opposite effect, i.e., it produces a phase
delay. Consequently, travelers tend to
synchronize their bodily rhythms at a speed of
1.5 h a day after westward and 1 h a day after
eastward flight irrespective of whether they
travel during the day or at night.
Signs of jet lag
 Reduced alertness,
 Daytime fatigue,
 Loss of appetite,
 Reduced cognitive skills
 Disruption of the sleep/wake cycle.
Potential mechanisms of circadian clock-dependent regulation of
neurodegenerationThe circadian clock regulates metabolism, ROS
homeostasis, DNA repair and, probably, autophagy (circadian clock
controlled systems and pathways are shown in green). Disruption of
circadian system function will compromise the activities of these systems,
which will lead to oxidative stress (shown in red) and accumulation of intraand
extra-cellular aggregates in the brain. This in turn will lead to brain cell
death and degeneration of brain structures (shown in yellow). Similar
mechanisms can contribute to the changes in the brain during the normal
ageing.
Nature, 491 (2012), pp. 348–356
Nature, 491 (2012), pp. 348–356
Potential mechanisms of circadian clock-dependent regulation of
neurodegenerationThe circadian clock regulates metabolism, ROS
homeostasis, DNA repair and, probably, autophagy (circadian clock
controlled systems and pathways are shown in green). Disruption of
circadian system function will compromise the activities of these systems,
which will lead to oxidative stress (shown in red) and accumulation of intraand
extra-cellular aggregates in the brain. This in turn will lead to brain cell
death and degeneration of brain structures (shown in yellow). Similar
mechanisms can contribute to the changes in the brain during the normal
ageing.
Potential pathways by which circadian dysregulation may mediate psychosocial
effects on cancer progression
 Arrow (A) represents activation of endocrine
stress-responses associated with psychological
distress and other psychosocial factors. Repeated
stress-response activation may hypothetically lead
to dysregulation of circadian rhythms (B), while
aberrations in sleep–wake cycles, rest-activity
rhythms, genetic, or suprachiasmatic control of
circadian rhythms would engender endocrine
abnormalities (C). Hypotheses regarding direct
effects of hormones on tumor growth involve
metabolic pathways or influences on oncogene
expression (D).
Potential pathways by which circadian dysregulation may mediate psychosocial
effects on cancer progression
 Neuroimmune effects are widespread and include
modulation of innate immunity, T and B cell function,
cytokine and adhesion molecule expression, cell trafficking,
and immune cell differentiation (E). Circadian rhythm
aberration is associated with abnormalities of immune cell
trafficking and cell proliferation cycles (F). It has been
hypothesized that circadian clock genes are tightly linked
with genes related to tumor growth and that tumors may be
a direct consequence of circadian dysregulation (G).
Immune defenses against tumor growth include both specific
mechanisms (e.g., killing by cytotoxic T lymphocytes aided
by helper T cells, B cell-mediated antibody-dependent lysis)
and non-specific immunity (e.g., lytic activity of NK, LAK, and
A-NK cells, macrophages, and granulocytes; H).
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