Binyrehormoner ) Binyrebarkhormoner

v/Jan Oxholm Gordeladze
• Binyrebarkhormoner
• Glukokortikoider
• Mineralokortikoider
• Kjønnshormoner (androgener)
• Binyremarghormoner
• Katekolaminer (Adrenalin, Noradrenalin)
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© 2005 Elsevier
• Binyrebark og –marg: separate celler i felles kjertel
på/ved siden av øvre nyrepoler (adrenal, suprarenal
• Separate deler av barken: ytre lag er zona glomerulosa,
midtre lag er zona fasciculata, indre lag er zona
• Produserer steroidhormoner (kortisol, aldosteron,
• Innerst ligger binyremargen, produserer katekolaminer
Cerebral regulering
• Overordnete stressutløsere
• Emosjoner, kognitive responser
• Homeostatiske stressutløsere
• Blodtap, sirkulatorisk sjokk etc.
(HPA – hypothalamic-pituitary-adrenal axis)
• ”Feedback” og ”feed-forward” regulering av
ACTH frisetting
• ”Stress” definert som stimuli som øker ACTH
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© 2005 Elsevier
POMC-genet (pro-opiomelanocortin)
ACTH (adrenocorticotropin)
MSH (melanocyttstimulerende hormon)
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© 2005 Elsevier
Downloaded from: StudentConsult (on 30 January 2011 02:17 PM)
© 2005 Elsevier
Downloaded from: StudentConsult (on 30 January 2011 02:17 PM)
© 2005 Elsevier
• Naturlige (kortisol, kortikosteron)
• Syntetiske (prednison, dexamethason)
Metabolic effects of Cortisol
• Anti-insulin action
• Protein catabolism
• Increased gluconeogenesis and
• No effects on CNS and heart
Cushings’ syndrome
Excess Cortisol
Protein catabolsim, buffalo hump
Moon face
Cushing's syndrome.
This is caused by
excessive exposure
to glucocorticoids,
and may be caused by
disease (e.g. an
tumour) or by
administration of
glucocorticoid drugs
Cushing's). Italicised
effects are
particularly common.
Less frequent
effects, related to
dose and duration of
therapy, are shown in
Antiinflammatory Pharmacologic
• Strong antiinflammatory effect via multiple pathways
• Resistance to ”stress”
Glucocorticoids and the Immune
• Immune System:
• Increase in intravascular leukocyte
• Decrease in migration of inflammatory cells to
sites of injury
• Suppression of immune system (thymolysis;
suppression of cytokines, prostanoids, kinins,
serotonin, histamine, collagenase , and
plasminogen activator)
Activation of the hypothalamic–
pituitary–adrenal axis and the sympathetic nervous
system (SNS) leads to the release of cortisol and
adrenaline from the adrenal cortex and medulla,
respectively. These hormones inhibit the release
of tumour necrosis factor (TNF) by monocytes.
Interleukin-6 (IL-6) produced by contracting
skeletal muscle also downregulates the
production of TNF by monocytes and may
stimulate further cortisol release.
Acute elevations in IL-6 stimulate
the release of IL-1 receptor antagonist (IL-1RA)
from monocytes and macrophages, thus
increasing the circulating concentrations of
this anti-inflammatory cytokine. Exercise training
mobilizes regulatory T (TReg) cells (which are a
major source of the anti-inflammatory cytokine IL10) and decreases the ratio of inflammatory
(CD14hiCD16−) monocytes.
CD14hiCD16− monocytes express less Toll-like
receptor 4 (TLR4), and thereby induce a reduced
inflammatory response marked by lower levels of
pro-inflammatory cytokines and reduced adipose
tissue infiltration.
Exercise also increases plasma
concentrations of key inflammatory immune cell
chemokines; repeated elevations of such
chemokines may lead to a downregulation of their
cellular receptors, resulting in reduced tissue
infiltration. A reduction in adipose tissue mass
and adipocyte size, along with reduced
macrophage infiltration and a switch from an
M1 to an M2 macrophage phenotype, may
contribute to a reduction in the release of proinflammatory cytokines (such as IL-6 and TNF)
and an increase in the release of anti-inflammatory
cytokines (such as adiponectin and IL-10) from
adipose tissue.
The effect of a healthy diet and physical exercise
on inflammatory processes
A healthy diet and physical activity maintain the anti-inflammatory phenotype of adipose tissue, which is marked
by small adipocyte size and the presence of anti-inflammatory immune cells, such as M2-type macrophages and
CD4+ regulatory T (TReg) cells. A positive energy balance and physical inactivity lead to an accumulation of
visceral fat and adipose tissue infiltration by pro-inflammatory macrophages and T cells. The pro-inflammatory M1
macrophage phenotype predominates and inflamed adipose tissue releases pro-inflammatory adipokines, such as
tumour necrosis factor (TNF), which causes a state of persistent low-grade systemic inflammation. This may
promote the development of insulin resistance, tumour growth, neurodegeneration and atherosclerosis.
Atherosclerosis is exacerbated by the deleterious changes in the blood lipid profile that are associated with a lack
of physical activity. LDL, low-density lipoprotein; IL-6, interleukin-6;TLR, Toll-like receptor.
RAA = Renin,
(forklaring av
figuren på
neste slide)
Control of aldosterone secretion
• Three pathways (in three different colours)
stimulate the glomerulosa cells of the
adrenal cortex to secrete aldosterone.
ACE, angiotensin-converting enzyme;
ACTH, adrenocorticotropin hormone; AVP,
arginine vasopressin; CRH, corticotropinreleasing hormone.
I følge semesterboka: læringsmål
• Addison’s syndrom
• Pheochromocytoma
Multiple choice 1-7:
Which of the following statements is/are false
Higher centra (via physical emotional and biochemical stimuli) may affect the secretion of CRH
(corticotropin releasing hormone), while diurnal «variation» of signals from the hypothalamus does not.
Cortisol negatively modulates CRH- and ACTH-secretion from the hypothalamus and the pituitary,
The secretion of ACTH is a Ca2+-mediated process stimulated by the cAMP-PKA axis, while the synthesis
and secretion of cortisol from the adrenals are mediated activation of a tyrosin kinase (acting via rasproteins), which may lead to cortisol producing tumours, also affecting the secretion of adrenalin and sex
The POMC-gene also codes for MSH, which is responsible for the pigmentation of the skin seen in the
elderly, when cortisol levels are diminished.
Cortisol blood levels are high in the morning and low in the evening.
Cortisol affects the health of multiple organs: bone and muscle mass (negatively), cartilage mass
(positively), immune cells (negatively), maintains cardiac output and glomerular filtration.
ACTH also affects the secretion of aldosterone, while not as effective as the renin-angiotensin system and
plasma K+-levels.