Samenvatting
Summary Advanced endocrinology
- Instelling
- Radboud Universiteit Nijmegen (RU)
Summary of Advanced endocrinology, given in the master Human biology.
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Voorbeeld 3 van de 20 pagina's
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Voorbeeld van de inhoud
The emergence of hormonesHormone = chemical substance produced by an endocrine cell/gland, that via the blood
circulation reaches organ and activates/inhibits the activity of that organ.
● Exocrine → sweat gland, to outside world
● Endocrine → vet/testis/adrenal, product to blood
Glands:
● Canonical → thyroid etc.
● Non-canonical → gastrointestinal tract, cells that release hormones and
the heart
GHRH released from hypothalamus and triggers the pituitary to make GH. GH activates cells
in tissues to make other hormones like IGF-1.
ANP is released by the atria of the heart and targets the kidneys.
Leptin is produced by fat cells and informs the brain about mass of fat (storage of energy).
Anesthetize animal → take out blood → plastic in vessels → plastic eats away
vessel walls → plastic cast.
Red blood cell velocity → GFP construct next to promoter and label vessels.
⇒ Blood vessels are an indicator for amount of blood cells.
Oxygen consumption → cells metabolically active.
Interactome → not only signal-receptor.
Hormone has to be transported or fused through the vessel wall → shuttling.
Local mediators:
● Auto feedback → autocrine action
● Targets neighbouring cells → paracrine action
● Action on the cell, without leaving the cell →
intracrine action
- Signal peptide binds to PTHrP/NLS
(needed to get it out of the cell) →
binds to PTH1R → activates p27Kip1 →
inhibits Rb phosphorylation, E2F
driven transcription and vascular
smooth muscle cell proliferation (can
lead to breast cancer).
- Without signal peptide PTHrP/NLS go
into the nucleus → c-Myc transcription
→ Cullin 1 etc transcription →
inhibition of p27Kip1.
⇒ NLS (nuclear localization signal) →
required for intracrine actions
,Neuroendocrine signaling → neurohormones are released into the bloodstream
and trigger the responses in target cells anywhere in the body.
Membrane components of early evolution turned into more complex organisms.
Amphiphilic molecules form micelles and bilayers in aqueous environments. Vesicles
capture pyranine (fluorescent dye).
Self-assembling amphiphilic building blocks → precursors for hormones.
Membrane phospholipids are modified by lipases for signalling.
Lipids as signals:
● Phosphatidylinositol and its phosphorylated derivatives regulate cell structure and
metabolism
● Eicosanoids (involved in reproduction, inflammation, fever, pain, blood pressure
regulation, gastric acid secretion etc.) are paracrines derived from membrane
phospholipids
Microbial group behaviors:
● Symbiosis
● Virulence
● Competence
● Conjugation
● Antibiotic production
● Motility
● Sporulation
● Biofilm formation
Communication in bacteria:
● High cell density → increase density of bacteria - increase of signals -
signals above threshold - activate gene complex
● Quorum sensing → ability to detect and to respond to cell population density by
gene regulation. Enables bacteria to restrict the expression of specific genes to the
high cell densities at which the resulting phenotypes will be most beneficial
Animal evolution:
● Multicellularity (in metazoa) and the formation of at least two seperate tissue layers
● Clear plane of symmetry (radial, bilateral) in Eumetazoa → more cell,
tissue and organ development, especially the gut
● Development of bilateral symmetry → clear anterior-posterior axis and
head formation, three tissue layers
Steroids as primordial biomolecular signals? → derive from cholesterol
Steroids in prokaryotes:
● Blue-green algae → cholesterol
● Mycoplasmas → require cholesterol
● Comamonas testosteroni → steroid-inducible genes
Steroids in invertebrates:
● Many invertebrate classes → biotransformation of steroids is similar to that
in vertebrata
, ● Insects → endogenous steroid ecdyson controls moulting and
metamorphosis. Reproductive cycle of rabbit flea is affected by exogenous
sex steroids and cortisol from its host
● Molluscs → sex steroids detected in gonads. Injection of testosterone
induces spermatogenesis in Lymnea and Helix
All vertebrates share conserved steroid hormone synthesis
pathways.
Cholesterol synthesis starts with squalene and
requires O2. Squalene is oxidatively converted to
oxido-squalene, which is cyclased to one of two
protosterols: cycloartenol or lanosterol.
Looking for squalene precursors → Miller-Urey
spark-discharge experiment: under certain
conditions, complex amino acids can arise. AA
can form polypeptides when heated.
Membranes can be formed from proteinoids.
Two pathways to squalene → from acetyl-CoA or
from glyceraldehyde-3-phosphate and pyruvate.
Plasma membrane composition:
● Archaea → branched polyprenic diphytanyl-glyceryl phospholipids and
other polyterpenyl ethers
● Bacteria → diacyl phospholipids and hopanoids
● Eukaryotes → diacyl phospholipids and cholesterol
Terpenes and terpenoids are squalene precursors. Terpenoids can dimerize/polymerize to
form squalenes. Squalene can form hopanoids and cholesterol-precursors that contain cyclic
structures.
The emergence of endocrinology
Thyroid → one of the first recognized glants.
Goiter → swollen thyroid: iodine-rich food helps with cretinism (severe mental
retardation caused by thyroid dysfunction during development and early life
stages).
Negative feedback-loop: T4 decreases it own function.
When dysfunctional, the thyroid keeps producing
thyroid hormones (swelling). Iodine suppletion → less
hormones.
Thyroid extract treatment → increase O 2 consumption
(basal metabolic rate).
One of first known functions of thyroid hormone →
induction of metamorphosis in amphibians.
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