This summary of the Advanced Endocrinology course is exceptionally detailed, offering a comprehensive overview of critical concepts in the field. It effectively covers the historical development, hormonal mechanisms, clinical applications, and the latest research advancements, making it a valuable ...
Lecture 1 – The history of endocrinology
The discovery of endocrinology is estimated to be around < 1000 BC,
where the ancient Egyptians understood the role of ovaries and gonads in
sexual reproduction. They figured out, by performing experiments, that
the removal of the ovaries led to no pregnancy and the removal of the
testicles led to a typical phenotype. A few centuries later the ancient
Romans, used organotherapy to treat epilepsy by eating brain and to treat
impotence by eating testicles. Scientist Cladius Galenus (ca. 210-131 BC)
found that there is a particular substance that travels from the brain
through the bloodstream. Moreover, this led to his discovery of the
pituitary gland and the thyroid gland. During the dark and Middle Ages,
the Chinese discovered a cure for goiter (vergrote schildklier) by
consuming enough seaweed and shellfish (rich in iodine). Moreover, they
made the correlation for the cause of diabetes between diabetes and high
carbohydrate intake.
1.1 The discovery of the first hormone
The first endocrine disease was discovered in 1849 by Thomas Addison,
known as Addison’s disease. This disease is characterized by
hyperpigmentation, salt craving, fatigue,
mood swings, and many more. Secretin
was discovered during a famous experiment
called “the crucial experiment” by Ernest
Starling and William Bayliss in 1902. They
hypothesized that there must be a second
messenger in the duodenum that stimulates
secretion by the pancreas. They injected
acid from the jejunum into a vein and found
the the secretion of the pancreas increased
significantly. (pH = -log[H+]). When the
duodenum encounters a pH that is too low,
the duodenal S cells will produce secretin
that travels via the bloodstream to the
pancreas. Here secretin triggers the
pancreas to produce NaHCO3 solution that neutrlizes the acidic
environment in the duodenum.
1.2 Hunger is just a hormonal
reaction
In 1999 two scientist made the discorvery of
the hormone ghrelin. Ghrelin, also known as
the ‘hunger hormone’ was discovered through
research focused on growth hormone
, secretagogue receptor (GHS-R) in the pituitary gland, which was an
orphan receptor (meaning its ligand was unknown. This receptor was
interesting because it could be activated by synthetic molecules known as
growth hormone secretagogues. The search for the ligand led them to the
stomach where they succesfully isolated and identified ghrelin. After
isolation, amino acids sequencing was performed which showed an
unknown 3rd amino acid. DNA analysis showed that the amino acid should
be serine, which is added when the protein is modified. Synthetic ghrelin
is lighter than natural ghrelin due to the missing modification. When blood
sugar levels are low, the stomach produces ghrelin, which then travels to
the pituitary gland where it binds to GHSR. The GHSR than relays the
signal to the hypothalamus, leading to the production of growth hormone.
The growth hormone travels via blood to the liver, causing the liver to
breakdown glycogen into glucose.
1.3 High blood sugar? Just have some insulin
The hormone insulin was discovered in 1929 by two scientist Banting and
MacLeod, who both shared a Nobel prize for their discovery. The synthesis
of insulin consists of a complex multistep process:
1) The insulin peptide is translated in the cytosol are preproinsulin,
which then is translocated to the ER lumen.
2) Preproinsulin contains a signal peptide that helps with the
translocation but is cleaved off when it reached the ER, converting
preproinsulin into proinsulin. Proinsulin is then folded into the right
conformation, creating di-sulfide bonds.
3) The correctly folded proinsulin is then transported to the Golgi
apparatus.
4) In the Golgi apparatus the proinsulin undergoes further modification,
where it is cleaved by a protease, liberating C-peptide.
5) Finally, carboxypeptidase E cleaves the proinsulin, resulting in the
formation of mature insulin.
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