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Endocrinology
Lecture Notes
Endocrinology
• The main function of the endocrine
system is to maintain the homeostasis
of the internal environment.
• Hormone: chemical messengers
secreted by cells of endocrine glands
and tissues that regulate the activity of
other cells in the body.
Endocrine Glands that function
Primarily to Secrete Hormones
•
Pituitary gland: secretes Anti-diuretic Hormone (ADH), oxytocin and
trophic hormones.
•
Thyroid gland: secretes thyroxin, tri-iodothyronine and calcitonin.
•
Parathyroid gland: secretes parathyroid hormone.
•
Adrenal gland: secretes cortisol, aldosterone, epinephrine and
androgens.
•
Pancreas: secretes insulin and glucagon.
•
Ovaries and testicles: androgens, estrogens and progesterone.
•
Pineal gland: melatonin.
•
Thymus gland: thymosine.
Other Organs Which Function
Secondarily As Endocrine Glands
• Heart: secretes atrial natriuretic peptide
(ANP) , it is secreted when there is an
expansion in blood volume. It causes diuresis,
so you lose Na in the urine. By losing Na in the
urine water is dragged with it. so the increase
in the blood volume is corrected.
• Kidney: secretes erythropoietin. This
hormone stimulates the bone morrow to
produce more red blood cells wherever there
is a low RBC mass.
Other Organs Which Function
Secondarily As Endocrine Glands
• Liver: secretes somatomedin which is a growth
factor.
• Skin: secrets D3 1,25-dihydroxyvitamin D3 which is
responsible for calcium homeostasis.
• Gastrointestinal tract: secrets gastrin, CCk, and VIP.
• Adipose tissue:secrets leptin which plays a role in
obesity.
• Hypothalamus: releasing and inhibiting hormones.
Chemical Classification of Hormones
1- Protein and peptide hormones:
 Like insulin.
 Usually present as prohormone, they become
the active form of the hormone later.
 Polar (hydrophilic).
Chemical Classification of Hormones
2- Steroid hormones:
 Like aldosteron, sex steroids hormones and
cortisol.
 they all have a back bone of cholesterol.
 Non polar, so they cross the cell membrane
easily.
Chemical Classification of Hormones
3- Tyrosine derivatives:
 Like catecholamine and thyroid hormone.
 They both have tyrosine backbone
 Thyroxin is nonpolar and crosses the cell membrane
easily
 Epinephrine usually have receptors on the cell
membrane.
Mechanism of Hormone Action
Functional categories of hormones based
on the location of their receptor
proteins and mechanisms of action:
1. Hormones that bind to nuclear receptor
proteins
2. Hormones that use second messengers.
Hormones That Binds to Nuclear Receptor
Proteins
Steroids:

Secreted by adrenal cortex, testes and ovaries

Steroid hormones are nonpolar ,hydrophobic (lipophilic), so
they need to be carried in the plasma by some sort of protein
that will carry them from one place to another. The carrier
protein binds to the hormone and carry it to the target call.
Once it reaches the target cell the hormone is released. It
goes inside the cell to bind to receptors which are present
either on the cytoplasm or the nucleus. Once the hormone
bind to the receptor it is taken to the nucleus, released and
then it binds to a domain on the DNA . This will stimulate
transcription and protein synthesis.
Hormones That Binds to Nuclear Receptor
Proteins
Thyroid Hormones:

Secreted by thyroid gland.

Location of receptor proteins is in the nucleus of the target
cells.

Very similar to steroids in size, being non-polar and very water
insoluble.

Carried mainly by thyroxine-binding globulin (TBG; T4 more
than T3
Hormones That Use a Second
Messengers



Catecholamines (epinephrine and norepinephrine)
Polypeptides
Glycoproteins
They are secreted all glands EXCEPT adrenal cortex, gonads
and thyroid.
Those can’t cross the lipid bilayer of cell membrane. So they
need receptors which are present on the outer surface
of the cell membrane.
Once the hormone binds to the receptor, several changes
occur in the cytoplasmic side of the cell membrane which
then stimulates a second messenger which can be cAMP , c-GMP, phospholipase C, Ca2+ and thyrosine
kinase.
Properties of Different Classifications of
Hormones
Storage:

Steroids: a very little storage of the hormone,
usually they are produced whenever we need them.

Thyroxine: it is usually stored for a much longer
period in the thyroid gland, about several weeks.

Peptides, proteins and catecholamines: their
storage is very short, can range from one day to
several days.
Properties of Different Classifications of
Hormones
Mechanism of secretion:

Steroids: once we need them they are released by
diffusion through the plasma membrane.

Thyroxine: it is secreted by proteolysis of thyroglobulin,
once we need them we need to breakdown thyroglobulin,
by breaking it we will have the release of thyroxine and
triiodothyronine.

Peptides, proteins : usually stored in vesicles and once
we need them they are secreted by exocytosis.

Catecholamines : usually stored in vesicles and once we
need them they are secreted by exocytosis.
Properties of Different Classifications of
Hormones
Binding to plasma proteins:

Steroids: Because they are non-polar, hydrophobic, lipophilic,
we rarely find them in the free form in the circulation, so,
they need plasma proteins.

Thyroxine: Because they are non-polar, hydrophobic, lipophilic,
we rarely find them in the free form in the circulation, so,
they need plasma proteins.

Peptides, proteins : Because they are polar, hydrophilic most
of them do not need plasma proteins to bind to. Only some
may need.

Catecholamines : they do not need any sort of plasma proteins.
Properties of Different Classifications of
Hormones
Mechanism of secretion:

Steroids: once we need them they are released by
diffusion through the plasma membrane.

Thyroxine: it is secreted by proteolysis of thyroglobulin,
once we need them we need to breakdown thyroglobulin,
by breaking it we will have the release of thyroxine and
triiodothyronine.

Peptides, proteins : usually stored in vesicles and once
we need them they are secreted by exocytosis.

Catecholamines : usually stored in vesicles and once we
need them they are secreted by exocytosis.
Properties of Different Classifications of
Hormones
Lifetime in the blood plasma 1/2t:

Steroids: Because the are bound to plasma proteins
their half life in the blood is about hours.

Thyroxine: Because the are bound to plasma proteins
their half life in the blood is about days.

Peptides, proteins : Because they are rarely bound to
plasma proteins or not at all their half life in the blood
is about minutes.

Catecholamines : Because they are not bound to plasma
proteins their half life in the blood is about seconds.
Properties of Different Classifications of
Hormones
Receptors:

Steroids: either on the cytoplasm or the nucleus.

Thyroxine: on the nucleus.

Peptides, proteins : Because they can not pass the
plasma membrane their receptors are on the plasma
membrane.

Catecholamines : Because they can not pass the
plasma membrane their receptors are on the plasma
membrane.
Properties of Different Classifications of
Hormones
Mechanism of action:

Steroids: Receptor-hormone complex controls
transcription.

Thyroxine: Receptor-hormone complex controls
transcription.

Peptides, proteins : Hormone binding triggers
synthesis of cytolic second messengers or protein
kinase activity.

Catecholamines : Hormone binding causes change in
membrane potential or triggers synthesis of cytolic
second mesengers.
Hormonal Rhythm
It is the pattern of secretion of the
hormone
Even though hormones have rhythms, the
hormone secretion is pulstile. Meaning
that the hormone is secreted then
stopped, secreted then stopped and so
on, just like pulse.
Circadian or diurnal Rhythm
It means that the hormone is secreted every 24 hours.
Examples:

Cortisol: is secreted around 5 am, about 2 hours
before waking up. Cortisol secretion depends on
what we call light-dark cycle.

Prolactine (PRL): is similar to cortisol.

Growth Hormon (GH): peaks during stages 3 and 4
of sleep wether at night or at day. It is known as
the sleep-wake cycle.
Ultradian Rhythm
It means that the hormone is secreted every ½, one or
two hours.
Examples:

LH

FSH

Testosterone
Infradian Rhythm
It means that the hormone is secreted any time more
than 24 hours.
Examples:

Menstruation or seasonal breeding in animals
Methods of Hormone Study
Bioassay: measures the potency of a hormone by quantifying a
biological effect produced by the hormone. It is not done in
clinics on humans.

Example: removing the pituitary gland which produces Growth
Hormone from a rat to see the effect of that hormone.
Followed by giving the animal that hormone to observe what
happens on the animal. Such as the elongation of bones or the
changes in blood glucose levels, which are the biological
effects of Growth Hormone.
Radioimmunoassay (RIA): uses radioactive marker and hormonespecific monoclonal antibodies. Sensitive, specific, precise and
convenient.

Example: when taking blood serum from a patient , then adding
a radioactive marker to it. The radioactive marker will
compete with the hormone tested for the antibody.
Methods of Hormone Study
Radioreceptor assay: same as RIA except a preparation of
hormone-specific receptors instead of hormone-specific
antibody.
Enzyme-linked Immunoabsorbent assay (ELISA): same as RIA
except we use an enzyme instead of a radioactive marker.
The enzyme activity is measured so that the amount of
hormone can be calculated.
High-performance liquid chromatology: separates the hormone
from a mixed solution (e.g. plasma) in a fractionating column.
The amount of hormone can then be measured. The
disadvantages are that it is expensive and slow.
Pituitary Gland
(Hypophysis)
The pituitary gland is connected to the
hypothalamus by an infundibulum. It is
structurally and functionally divided into 2
lobes:

Anterior hypophysis (Adenohypophysis).

Posterior pituitary or neurohypophysis ( neural of
the pituitary; pars distalis).
Posterior Pituitary Hormones
Posterior pituitary secretes only 2
hormones which are:
 Produced in the Paraventricular and
supraoptic nuclei of the hypothalamus.
 Stored and secreted by the posterior
pituitary.
Posterior Pituitary Hormones
Antidiuretic hormone (ADH):



Also known as arginine vasopressin (AVP)
It stimulates retention of water by the kidneys
At high doses, it causes vasoconstriction of blood vessels.
Oxytocin:
In females:

It stimulates the contraction of the uterus during labour, required
for childbirth

It stimulates milk-ejection reflex in a lactating woman, i.e.,
contractions of the mammary gland alveoli and ducts.
In males:

Secreted during ejaculation, due to its effect on the uterus , it
causes the contraction of the female uterus , therefore it will aid in
the sperm going up into the fallopian tube to fertilize an egg.
Control of ADH & Oxytocin Secretion
By Neuro-endocrine reflex
Oxytocin secretion:
The baby is suckling a mother’s breast  touch
receptors located on the nipple send sensory
signals to the hypothalamus  oxytocin is
released  causes milk ejection.
When the baby stops suckling  milk ejection
stops
Control of ADH & Oxytocin Secretion
By Neuro-endocrine reflex
Control of ADH secretion:
High osmolarity stimulates ADH .
When we have high osmolarity  water will leave the
osmoreceptors  so they will shrink  this
shrinking will stimulate the hypothalamus to
produce ADH  that will be secreted from the
posterior pituitary.
ADH will act on the collecting duct of the kidney to
cause water retention and decrease water
excretion. That will decrease osmolarity and
eventually correct it.
Control of ADH & Oxytocin Secretion
By Neuro-endocrine reflex
Control of ADH secretion:
Increased blood volume
When we have high an increase in blood volume  it is
sensed by receptors present in the left atrium of
the heart  it will send signals to the hypothalamus
telling it to stop producing ADH.
There will be water excretion.
There will be an inhibition of ADH.
Anterior Pituitary Hormones
Secreted by pars distalis of adenohypophysis






Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Prolactine
Growth hormone (GH)
Anterior Pituitary Hormones

TSH acts on the thyroid gland to produce T3 and T4.

ACTH acts on the adrenal gland to secret Glucocorticoids
(cortisol), mineralocorticoids (aldosterone) and sex steroids.

GH does not have a certain gland to act on . It acts all over
the body.






It stimulates the liver to produce IGF-I
It acts on different organs and tissues of the body such as
bones, muscle, adipose tissue
GH is anabolic on proteins ,it will increase protein metabolism.
GH is catabolic on carbohydrates and lipids. Meaning that it will
increase blood concentration of glucose and free fatty acids.
It has an anti-insulin effect, it stimulates carbohydrates
breakdown.
If you have hypersecretion secretion of GH it will cause
hyperglycemia.
Anterior Pituitary Hormones
 Prolactine acts on the breasts.
 It stimulates breast development during
pregnancy (not during puberty).
 In men it facilitates reproductive function.
 If men have high levels of prolactin, breasts will
develop. These men become infertile because
high levels of PRL interfere with the secretion of
LH and FSH which are needed for
spermatogenesis in males.
Anterior Pituitary Hormones
 LH: acts on gonads
 In females: it stimulates ovulation and
conversion of ovulated ovarian follicle into
corpus luteum.
 In males: it stimulates the secretion of
male sex hormones (mainly testosterone)
from leydig cells in testes.
Anterior Pituitary Hormones
 FSH: acts on gonads
 In females: it stimulates the growth
of ovarian follicle. It acts during the
first part of the menstrual cycle.
 In males: it stimulates the
production of sperms in the testes.
 Hyposecretion of Growth Hormone
 During childhood  Pituitary dwarfism (with
normal body proportions)
 During adulthood  Simmonds’ disease
 Hypersecretion of Growth Hormone
 During childhood  Gigantism (longitudinal
growth of the bone because the epiphyseal plate
has not fused)
 During adulthood  Acromegaly (no further
growth but person’s appearance changes as a
result of thickening of bones, growth of soft
tissues as in face, hand and feet.
Control of Secretion of Anterior
Pituitary Hormones
1- hypothalamic control: achieved
through hormonal control.
2- Feedback control: by hormones
secreted from target glands.
 Hypothalamic control (Endocrine
control) of anterior pituitary
hormones.
 Control is hormonal.
 Hypothalamic releasing and inhibiting
hormones pass through the
hypothalamo-hypophyseal portal
system and regulate secretions of
anterior pituitary.






Thyrotropin-releasing hormone (TRH) stimulates
the secretion of TSH.
Corticotropin-releasing hormone (CRH) stimulates
the secretion of ACTH.
Gonadotropin-releasing hormone (GnRH) stimulates
the secretion of LH and FSH
Growth hormone releasing hormone (GHRH)
stimulates GH secretion.
Somatostanin (SS) inhibits the secretion of Growth
hormone.
Prolactin is regulated by hypothalamic inhibitory
hormone known as Prolactin-inhibiting hormone
(PIH).
When cutting the connection between the
hypothalamus and the anterior
pituitary there will be a decrease in
all hormones except prolactine.
 Feedback control of anterior pituitary
Secretion of ACTH, FSH, LH and TSH is controlled
by negative feedback inhibition:
 Target gland hormones  hypothalamus
 Target gland hormones  anterior pituitary
 Anterior pituitary  hypothalamus
Long loop negative feedback
 Target gland hormones  anterior pituitary 
hypothalamus
Short loop negative feedback
 Anterior pituitary  hypothalamus
Ultrashort negative feedback
 hypothalamus  hypothalamus
End of The First
Lecture