College aantekeningen
Lectures Experimental and Clinical Neuroendocrinology
- Instelling
- Vrije Universiteit Amsterdam (VU)
All lectures in the course Experimental and Clinical Neuroendocrinology, written in 2021
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Voorbeeld 4 van de 73 pagina's
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Voorbeeld van de inhoud
Lecture 1 – introductionFocus on the (patho)physiology, diagnosis, and treatment
of diseases of the hypothalamus and pituitary gland!!
Process
Input → process → output (+ feedback)
Secreting cell with hormone → blood vessel → hormone to receptor of target cell
For example: insulin & blood sugar level
Involved in: growth, puberty and reproduction, eating, stress, mood, sexuality, biological clocks
Hormones
- Peptide hormones (catecholamines)
o FAST
o Hydrophilic & lipophobic, cannot cross membrane
▪ Acts on membrane receptor, G-protein coupled (αβγ)
→ second messengers (signal transduction)
o Examples: insulin, glucagon, leptin, ADH, oxytocin
- Steroid hormones
o SLOW
o Lipophilic, can cross membrane (diffusion)
▪ Acts on receptor in nucleus/cytoplasm → complex
binds to hormone-response element (HRE) on DNA =
transcription factor
▪ N-terminal of nuclear receptor binds to DNA
o Examples: estrogen, progesterone, testosterone (produced by
gonads)
,Two steps feedback system:
Concentration TRH to Pituitary = HIGH
Concentration TRH to rest of the body (via periphery) = LOW
→ doesn’t play a role in rest of the body & can’t be measured in
peripheral blood
Agonists = drugs that occupy receptors and activate them
Antagonist = drugs that occupy receptors but do not activate them. Antagonists block receptor
activation by agonists
SERM (selective receptor modulators, f.e. estrogen), alpha and beta receptor for estrogen, present in
different body parts
→ does not activate all receptors, only uterus & not breast
Clinical endocrinology
Inverse to basic endocrinology
→ start with science & symptoms & complaints → hormonal disease possible cause? → blood testing + neuroendocrine
tests
Problem at level of hypothalamus, pituitary or target gland?
Central pituitary → peripheral thyroid gland = tropic hormones (no direct effect)
Peripheral thyroid gland → peripheral blood = peripheral hormones (direct effect on tissue)
o Central hyperfunction:
o trophic hormones increased → peripheral hormones increase (same effect)
o Central hypofunction:
o trophic hormones decrease → peripheral hormones decrease (same effect)
o Peripheral hyperfunction:
o peripheral hormones increase → trophic hormones decrease
(feedback loop)
o Peripheral hypofunction:
o peripheral hormones decrease → trophic hormones increase
(feedback loop)
Problem peripheral or central?
→ Both hormone levels increased/decreased = central
hyper/hypothyroidism
→ Both hormone levels controverse effects = peripheral
hyper/hypothyroidism
“Normal values” is partly dependent on reference levels, partly on the individual
(background of the complaints of the individual)
→ also on day night rhythm
Endocrine tests: stimulate/ inhibit the system
o Cushing disease (hypercortisolism)
o Dexamethasonetest (inhibition test, similar effect
as cortisol)
▪ Application of dexamethasone in
pituitary gland→ decrease ACTH →
decrease cortisol
▪ Cortisol not decreased? =
hypercortisolism (autonomous
production)
o Morbus Cushing: ACTH increased → cortisol
increased
o Adrenal Cushing: ACTH decreased → cortisol increased
o Addison’s disease (hypocortisolism)
o Synacthentest (stimulation test)
, ▪ Application of ACTH in adrenal gland → ACTH increased → cortisol increased
▪ Cortisol not increased? = hypocortisolism
o Central hypocortisolism: ACTH decreased → cortisol decreased
o Morbus Addison = ACTH increased → cortisol decreased
Acromegaly (varying growth hormone during the day)
, Lecture 2 – Evaluation of Pituitary
Function and novel developments in
hormone detection
Aims of this lecture:
• Know main principles of laboratory test validation
• Explain Synacthen test (=ACTH stimulation test)
• Be able to reflect on the analytical concepts of hormone measurements
• Appreciate the different (pre)analytical issues regarding hormone measurements
Posterior pituitary (neurohypophysis):
• Oxytocin
• Vasopressin
Anterior pituitary (adenohypophysis):
• GH
• PRL
• LH
• FSH
• ACTH
• TSH
-> through portal system
The posterior pituitary is a lobe of the gland that is
functionally connected to the hypothalamus by the median eminence via a small tube called the pituitary stalk (also called
the infundibular stalk or the infundibulum).
Evaluation of pituitary function:
Measure basal level of hormones -> does not tell you too much due to circadian rhythm
→ Perform dynamic function test:
• Challenge the system
• Test feedback system
• Circumvent pulsatile release
Synacthen test -> ACTH stimulation test -> increases cortisol levels -> cortisol should
be above certain value, if below -> adrenal insufficient
Diagnostic laboratory:
ISO15189 validation → Confirmation through the provision of objective evidence, that the requirements for a specific
intended use or application have been fulfilled.
Need to validate -> PATLMCRD
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