Lecture 1: The Emergence and History of Endocrinology
Studying of endocrinology before they knew it was endocrinology was done by either
extirpation (removal) or replacement in ancient egypt (<1000 BC)
→ to understand the role of gonads in sexual reproduction
- first extirpation experiments where:
- The removal of ovaries: resulted in no pregnancy
- The removal of testes: resulted in a distinct phenotype (eunuchs serving in
the pharaoh’s harem)
- Also, pregnancy diagnosis by morning sickness → related to high plasma
levels of estrogen
- Detection of diabetes by ‘the passing of too much urine”
Roman period
- Organoectomy and organotherapy: resembles hormone replacement therapy
- Eating pig brain to treat epilepsy
- Eating testes to treat impotence
- Claudius Galenus (ca. 210-131 BC) was the first to describe endocrine organs and
made assumptions about their possible function
- Described the thyroid gland as a ductless gland (because an endocrine gland
always secretes its products directly into the bloodstream)
- He also described that ‘substances from brain being carried into the
blood’ → first written statement of endocrinology without knowing
- Described the pituitary gland as “storage of waste products from the brain”
- Peri Spermatos (“on seed”), by Claudius Galenus
- He described that castration resulted in decreased libido, changed fat
deposition and changes in body hair
- Also that substance from testis affected physical characteristics
Dark and middle ages
During the dark and middle ages nothing really happened in europe
→ Meanwhile in China
- They developed a cure for goiter (enlarged thyroid due to less functioning, = thyroid
hyperplasia) by
- Consumption of seaweed and shellfish: both rich sources of iodine
- They correlated the enlarged thyroid with dysfunction of the thyroid gland
- So, they treated it with dried thyroid glands
- They found the correlation with the carbohydrate metabolism in
cause of diabetes
- Performed testicular organotherapy
- They extracted bioactive compounds such as steroids and their
metabolites from urine, however, they did not know the nature
of these compounds
goiter: Thyroid: produces T-4 and T-3. This is controlled by the
pituitary gland and hypothalamus
, - hypothalamus: signals pituitary gland to make thyroid-stimulating hormone (TSH)
- Pituitary gland: located below hypothalamus, released TSH depending on how
much T-4, T-3 is present in the blood
- Thyroid gland: regulates hormone production (T-3, T-4) based on amount of TSH is
received from the pituitary gland
So, how does iodine supplementation treat goiter: not enough iodine → hormone
production drops → pituitary gland produces TSH to signal thyroid gland to
produce more hormone → increased signal results in thyroid growth.
Few centuries later, things started to be picked up → description of goiter and
cretinism
- cretinism: Severe congenital, mental and physical retardation caused by thyroid
dysfunction during development and early life stages
Thyroid gland: early misconceptions
- Wharton (1656): Thought that the thyroid gland produced a viscous fluid
which had as function to lubricate the trachea. In addition, he thought that
an enlarged thyroid gland had only a cosmetic function → “the gland is
larger in women to serve a cosmetic function in giving grace to the
contour of the neck”
- Rush (1820): Thought that the thyroid gland functioned as a reservoir to
diverge blood from the brain. He thought the reason for an enlarged gland
in women was “necessary to guard the female system from the influence
of the more numerous causes of irritation and vexation of mind to which
they are exposed than the male sex. → Hofrichter commented on this
statement (1820)
- “husbands would have learned to recognize the swelling of this gland as a
danger signal of threatening trouble from their better halves”.
Thyroid gland: a short chronolgy
1. 1600 BC (China), Galenus (Roman period)
a. Èating of marine sponges and algae (which are rich in iodine) to threat goiter
b. Goiter epidemics in the Alps treated with “sea weed therapy” (also rich in
iodine)
2. Wang Hei (1475)
a. Made an anatomical description of the thyroid gland
b. Treated goiter with dried thyroid glands
3. Prout (1811)
a. Iodine for goiter treatment
4. Magnus-Levy (1895)
a. Thyroid extracts increase O2-consumption (i.e. basal metabolic rate)
5. Gudernatsch (1911(
a. Thyroid gland regulates metamorphosis in amphibia
6. Kendall (1915), Harrington (1926)
a. Isolation and synthesis of thyroxine (T4, the prohormone)
7. Gross and Pitt-Rivers (1952)
a. Isolation and synthesis of tri-iodothyronine (T3, the bioactive thyroid hormone)
,One of the first known functions of thyroid
hormone → Induction of metamorphosis in
amphibians and also physiological and
behavioral metamorphoses
Salmon: fresh/ salt water transition →
under control of endocrine system: thyroid
hormone \
- results in completely different fish in:
looks, behavior and metabolism
Fresh water fish: bottom dweller, sedentary, low
metabolism, FW osmolarity
Salt water fish (adult): pelagic (open, free waters away from shore), migrating, high
metabolism, SW osmolarity
Thomas Addison (1849)
First to describe an endocrine disease, without knowing about hormone
= Addison disease: hyperpigmentation, salt craving, fatique, mood swings
→ Addison discovered that patients had failure of the adrenals without knowing
the adrenal function
He started the field of Clinical Endocrinology
Endocrine axis: hormone never on
its own! → always up/down
regulations, but almost all work via
negative feedback, so in the end,
there is self inhibition
, 1. So, first, neural input from stress or circadian clock (sets the rhythm of CRF
secretion)
2. Hypothalamus: secretes CRF
3. Pituitary gland: secretes ACTH
4. Adrenal gland: produces cortisol
Negative feedback loop: cortisol negatively regulates ACTH and CRF production, thus in the
end, self inhibition
Addison disease: defect in cortisol production, so no negative feedback, results in increase
in CRF and ACTH (so not only loss, but also gaining of other hormones)
How does this result in hyperpigmentation
- ACTH is generated from a pro-hormone (POMC)
- a-MSH is part of ACTH and can bind to the MC1R receptor (skin receptor) which
activates pigment production
- In high concentrations, ACTH will also activate MC1R → pigmentation
Charles-Edouard Brown-Sequard → Selling of animal parts
But also, injected this in himself → isolates from the testicles
- He detected improvement, however placebo effect: testicles contain only a low
concentration of testosterone as it is not stored in the testis.
However, he was one of the first to describe an endocrine organ: ”possessed by some
substance of substances which our blood owes to the testicles”.
Ivan Petrovitsj Pavlov → First Nobel Prize for Integrated Systems Physiology
Pancreas secretion by adding of hydrochloric acid (stomach acid) → resulted in
an increased secretion of pancreas (this was due to hormones, but he did not
know yet)
Studying of endocrinology before they knew it was endocrinology was done by either
extirpation (removal) or replacement in ancient egypt (<1000 BC)
→ to understand the role of gonads in sexual reproduction
- first extirpation experiments where:
- The removal of ovaries: resulted in no pregnancy
- The removal of testes: resulted in a distinct phenotype (eunuchs serving in
the pharaoh’s harem)
- Also, pregnancy diagnosis by morning sickness → related to high plasma
levels of estrogen
- Detection of diabetes by ‘the passing of too much urine”
Roman period
- Organoectomy and organotherapy: resembles hormone replacement therapy
- Eating pig brain to treat epilepsy
- Eating testes to treat impotence
- Claudius Galenus (ca. 210-131 BC) was the first to describe endocrine organs and
made assumptions about their possible function
- Described the thyroid gland as a ductless gland (because an endocrine gland
always secretes its products directly into the bloodstream)
- He also described that ‘substances from brain being carried into the
blood’ → first written statement of endocrinology without knowing
- Described the pituitary gland as “storage of waste products from the brain”
- Peri Spermatos (“on seed”), by Claudius Galenus
- He described that castration resulted in decreased libido, changed fat
deposition and changes in body hair
- Also that substance from testis affected physical characteristics
Dark and middle ages
During the dark and middle ages nothing really happened in europe
→ Meanwhile in China
- They developed a cure for goiter (enlarged thyroid due to less functioning, = thyroid
hyperplasia) by
- Consumption of seaweed and shellfish: both rich sources of iodine
- They correlated the enlarged thyroid with dysfunction of the thyroid gland
- So, they treated it with dried thyroid glands
- They found the correlation with the carbohydrate metabolism in
cause of diabetes
- Performed testicular organotherapy
- They extracted bioactive compounds such as steroids and their
metabolites from urine, however, they did not know the nature
of these compounds
goiter: Thyroid: produces T-4 and T-3. This is controlled by the
pituitary gland and hypothalamus
, - hypothalamus: signals pituitary gland to make thyroid-stimulating hormone (TSH)
- Pituitary gland: located below hypothalamus, released TSH depending on how
much T-4, T-3 is present in the blood
- Thyroid gland: regulates hormone production (T-3, T-4) based on amount of TSH is
received from the pituitary gland
So, how does iodine supplementation treat goiter: not enough iodine → hormone
production drops → pituitary gland produces TSH to signal thyroid gland to
produce more hormone → increased signal results in thyroid growth.
Few centuries later, things started to be picked up → description of goiter and
cretinism
- cretinism: Severe congenital, mental and physical retardation caused by thyroid
dysfunction during development and early life stages
Thyroid gland: early misconceptions
- Wharton (1656): Thought that the thyroid gland produced a viscous fluid
which had as function to lubricate the trachea. In addition, he thought that
an enlarged thyroid gland had only a cosmetic function → “the gland is
larger in women to serve a cosmetic function in giving grace to the
contour of the neck”
- Rush (1820): Thought that the thyroid gland functioned as a reservoir to
diverge blood from the brain. He thought the reason for an enlarged gland
in women was “necessary to guard the female system from the influence
of the more numerous causes of irritation and vexation of mind to which
they are exposed than the male sex. → Hofrichter commented on this
statement (1820)
- “husbands would have learned to recognize the swelling of this gland as a
danger signal of threatening trouble from their better halves”.
Thyroid gland: a short chronolgy
1. 1600 BC (China), Galenus (Roman period)
a. Èating of marine sponges and algae (which are rich in iodine) to threat goiter
b. Goiter epidemics in the Alps treated with “sea weed therapy” (also rich in
iodine)
2. Wang Hei (1475)
a. Made an anatomical description of the thyroid gland
b. Treated goiter with dried thyroid glands
3. Prout (1811)
a. Iodine for goiter treatment
4. Magnus-Levy (1895)
a. Thyroid extracts increase O2-consumption (i.e. basal metabolic rate)
5. Gudernatsch (1911(
a. Thyroid gland regulates metamorphosis in amphibia
6. Kendall (1915), Harrington (1926)
a. Isolation and synthesis of thyroxine (T4, the prohormone)
7. Gross and Pitt-Rivers (1952)
a. Isolation and synthesis of tri-iodothyronine (T3, the bioactive thyroid hormone)
,One of the first known functions of thyroid
hormone → Induction of metamorphosis in
amphibians and also physiological and
behavioral metamorphoses
Salmon: fresh/ salt water transition →
under control of endocrine system: thyroid
hormone \
- results in completely different fish in:
looks, behavior and metabolism
Fresh water fish: bottom dweller, sedentary, low
metabolism, FW osmolarity
Salt water fish (adult): pelagic (open, free waters away from shore), migrating, high
metabolism, SW osmolarity
Thomas Addison (1849)
First to describe an endocrine disease, without knowing about hormone
= Addison disease: hyperpigmentation, salt craving, fatique, mood swings
→ Addison discovered that patients had failure of the adrenals without knowing
the adrenal function
He started the field of Clinical Endocrinology
Endocrine axis: hormone never on
its own! → always up/down
regulations, but almost all work via
negative feedback, so in the end,
there is self inhibition
, 1. So, first, neural input from stress or circadian clock (sets the rhythm of CRF
secretion)
2. Hypothalamus: secretes CRF
3. Pituitary gland: secretes ACTH
4. Adrenal gland: produces cortisol
Negative feedback loop: cortisol negatively regulates ACTH and CRF production, thus in the
end, self inhibition
Addison disease: defect in cortisol production, so no negative feedback, results in increase
in CRF and ACTH (so not only loss, but also gaining of other hormones)
How does this result in hyperpigmentation
- ACTH is generated from a pro-hormone (POMC)
- a-MSH is part of ACTH and can bind to the MC1R receptor (skin receptor) which
activates pigment production
- In high concentrations, ACTH will also activate MC1R → pigmentation
Charles-Edouard Brown-Sequard → Selling of animal parts
But also, injected this in himself → isolates from the testicles
- He detected improvement, however placebo effect: testicles contain only a low
concentration of testosterone as it is not stored in the testis.
However, he was one of the first to describe an endocrine organ: ”possessed by some
substance of substances which our blood owes to the testicles”.
Ivan Petrovitsj Pavlov → First Nobel Prize for Integrated Systems Physiology
Pancreas secretion by adding of hydrochloric acid (stomach acid) → resulted in
an increased secretion of pancreas (this was due to hormones, but he did not
know yet)
