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Manifestation of Novel Social Challenges of the
European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University
of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Manifestation of Novel Social Challenges of the
European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University
of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Márta Balaskó-Erika Pétervári
Molecular and Clinical Basics of Gerontology – Lecture
13
CHANGES OF THE
ENDOCRINE SYSTEM
AND METABOLISM
PART I
TÁMOP-4.1.2-08/1/A-2009-0011
Age-related alterations in
the endocrine system
• The function of most endocrine organs
change (declines) in the course of
aging.
• Both baseline and reserve functions
become limited.
• Signal transduction mechanisms grow
diminished, hormone release and
hormone-induced responses are
suppressed.
• However, age-related alterations in
complex regulatory feed-back circles
TÁMOP-4.1.2-08/1/A-2009-0011
Common endocrine
alterations in the elderly
Menopause
Andro“pause”

Estrogen  FSH Testosterone

(ProgesteroneLH
DHT
?) Failing libido
depression
osteoporosis
QOL issues
Somatopause
GH 
Sarcopenia
lean
body mass
(appetite:
CCK)
Immuno-neuroendocrine
correlations
Adreno“pause”
DHEA 
DHEAS 
Cortisol 
ACTH
Metabolic
“Synchropause”
alterations
Melatonin
Insulin
Sleep(?)
QOL issues
certain
resistance,
autoimmune (inflammageing
IGT
processes 
)
Metabolic
syndrome
(Carcinogenesi
Not “normal” ageing process, but common:
s)
subclinical
hypo- and hyperthyroidism in the elderly
The somatotropic hormone system
in the elderly: aging vs.
growth hormone (GH)
TÁMOP-4.1.2-08/1/A-2009-0011
Age is associated with:
• a decline in spontaneous overnight GHsecretion,
• a reduced GH amplitude and low serum
insulin-like growth factor-I (IGF-I)
levels.
Changes in body composition with age are
similar to those observed in patients
with the adult GH deficiency syndrome.
Administration of GH to the latter group
of patients has significantly improved
body composition, muscle strength,
Ghrelin administration
improves the somatotropic
system in the elderly
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• Growth hormone (GH) secretagogues
(ghrelin, MK-0677) act on arcuate
neurons,
• they restore the amplitude of GH
pulsatility in old animals, thus GH
target tissues are exposed to youngadult GH pulsatility.
• Functional benefits include increased
lean mass, bone density and modest
improvements in strength,
• partially restored thymus function,
• partially restored hepatic function
(e.g. gluconeogenesis)
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Functions of the suprarenal
glands in the elderly
• Function of the hypothalamo-pituitaryadrenal (HPA) axis is not only
maintained, but rather enhanced in the
elderly possibly contributing [via
central actions of hypothalamic
corticotropin-releasing-factor (CRF)] to
prevalent anxiety in old populations.
• Diurnal rhythms of adrenocorticotrop
hormone (ACTH) and cortisol are
maintained, their release is enhanced.
• This slight hyperfunction may contribute
to adiposity, osteoporosis and
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Adrenopause
• Following the second and third decade of
life, there is a continuous decline of
adrenal androgen production (“adrenopause”).
• Adrenal androgens, dehydro-epiandrosterone
(DHEA) and its sulphate (DHEA-S), are the
most abundant steroid hormones in the human
body with largely unknown physiological
functions.
• Studies utilizing supplementation of DHEA
demonstrated clear benefits: e.g. in
autoimmune diseases, in Addison's disease, in
prevention of diabetes mellitus, in obesity,
cancer, heart disease.
• The issue of replacing DHEA in elderly still
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Sex steroids in the elderly
Sex steroids (estrogens and androgens
present in both gender) affect multiple
physiological functions from food
intake, metabolic rate and body
composition to thermoregulation and
neuronal functions.
There is an age-associated reductions
in sex steroids in both genders.
• In females, this reduction is rapid
leading to menopause and infertility
between the ages of 45-55 years (mean
51 years).
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Menopause
Concentrations of estrogens and
progesterone rapidly decline, those of
pituitary gonadotrop hormones follicle
stimulating and luteinizing hormones
(FSH and LH) rise.
Some estrogen is produced by fat tissue
aromatase from adrenal cortex derived
androgens.
Consequences include:
thermoregulatory disorders (hot
flashes), atrophy of estrogen-sensitive
Premenopausal
thermoregulation
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Stabilized thermoregulatory set point
Presynaptic neuron External factors
Hypothalamus
Adrenal gland
Estrogens
Ovary
Normal
thermoregulatory
response
Euthermia
(vasodilatation or
Postsynaptic neuron constriction)
Hyperthemic
perception
Hypothermic
perception
5-HT1a receptor5-HT2 receptor 5-HT
5-HT reuptake s
Peri/postmenopausal
thermoregulation
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Destabilized thermoregulatory set point, 5-HT?, imbalance of 5HT1a/5-HT2 receptors?
Presynaptic neuron External factors
Hypothalamus
Altered
thermoregulatory
response
Ovary
Adrenal gland
Estrogens
Menopause
Anti-estrogens
Aromatase
inhibitors
LHRH agonists
Hot flushes
Postsynaptic neuron (vasodilatation)
Hyperthemic
perception
Hypothermic
perception
5-HT1a receptor5-HT2 receptor 5-HT
5-HT reuptake s
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Andropause in the elderly
Reduction in male sex steroids with aging:
• may lead to alterations in body
composition and performance (frailty)
similar to those observed in non-elderly
hypogonadal men.
• does not prevent benign prostatic
hyperplasia (BPH), very frequently seen in
elderly men [dihydro-testosterone (DHT)
stimulate prostate cell proliferation].
• may allow for somewhat enhanced estrogen
production leading prostate hyperplasia in
animal experiments.
Administration of testosterone has been
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Benign prostate hyperplasia
(BPH) in the elderly
Definition, prevalence
• Benign hyperplasia of prostatic stromal and
epithelial cells leading to compression of the
urethra.
• BPH rarely causes symptoms before the age 40, but
prevalence of prostatic enlargement may reach more
than 50% above 60 years and as high as 80% above
the age of 80 years. (Enlargement does not mean
clinical symptoms.)
Pathogenesis
In addition to life-long androgene production
(especially that of DHT), age-related hormonal
changes (e.g. a significant rise in FSH production
and a relative increase in estrogen release)
promote cellular hyperplasia.
Benign prostate hyperplasia
(BPH): invariably common in
elderly
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Testosterone nmol/L
()
35
Cross of
andropause
2,500
30
20
1,500
15
1,000
10
500
5
0
young
old
0
FSH ng/L ()
25
2,00
0
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Benign prostate hyperplasia
(BPH): mechanisms
GnRH
Testes
LH/FSH
FSH
Pituitary
PRL/GH
FSH-R
PRL/GH-R
Testosterone
Autocrine
Estrogens
Endocrine
Paracrine
Endocrine
Aromatase
Androgens
Estrogens
Prostate
Exocrine
Auto/Paracrine
“Synchropause”:
definition, symptoms
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Definition
Healthy young individuals (humans and mammals)
show characteristic circadian rhythm regarding
body temperature, activity, blood pressure (BP),
endocrine functions (e.g. release of GH, ACTH,
etc.), sleep, etc.
In the elderly such circadian rhythmicity becomes
disturbed, most frequently affecting sleep,
activity, blood pressure.
Symptoms
• disturbances of sleep (advanced sleep-phase
syndrome, delayed sleep-phase syndrome)
• non-dipper BP pattern (night-time BP is higher
and not lower than day-time value)
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“Synchropause”:
pathogenesis, treatment
Pathogenesis is unknown
• Decline in melatonin production of the pineal
gland is assumed.
• Low day-time activity, prolonged daily bed-rest
Therapeutical measures
There is no cure for aging-associated
disturbances of circadian rhythm.
Benefits were shown using:
• bright light therapy
• behavior and chronoterapy (adjusting
activity/light and avoiding coffee/nicotine and
other stimulation before desired sleeping time)
• an increased level of physical activity (e.g.
fitness training program for 3 months)
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Thyroid dysfunctions in the
elderly
• Thyroid dysfunctions (especially of autoimmune
origin) are frequent, often without specific,
characteristic symptoms.
• Hyperthyroidism
Atrial fibrillation or cardiac decompensation
may be the first sign, eventually heat
intolerance may develop. Loss of BW is not
necessarily observed.
• Hypothyroidism often appears as depression,
confusion or dementia. Constipation is also a
characteristic finding. Osteoporosis is a
frequent long-term complication.
• Diagnosis and treatment are important.
• Upon treatment, hypothyroidism-associated
cognitive dysfunctions are reversible,