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Lecture 1 – Biochemistry – Endocrinology – 2nd Class- IBN HIAN Medical college 2016/2017
Endocrine Disorders
College of Medicine
IBN HIAN UNIVERSITY
Subject: Biochemistry / 2nd year Medicine/ 2016-2017
Dr. ABDUL HUSSEIN A. ALGENABI
MBChB, MSc, PhD
Clinical Chemistry
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Lecture 1 – Biochemistry – Endocrinology – 2nd Class- IBN HIAN Medical college 2016/2017
Objectives
•
Definition of Hormone
•
Chemical classification of hormones (H. structure)
•
Mechanism of hormone action (water solubility)
•
Major endocrine glands
•
Control of Hormone secretion
Hormone – is defined as a regulatory chemical substance secreted into the
blood by an endocrine gland. Paracrine - regulatory molecules work without
being transmitted by the blood – not endocrine
Hormone concentration in blood can be present in three forms; protein
bound form w is inactive, free (unbound) form w is the active form and total
form that's of bound and free (usually measured in laboratory).
Chemical Classification of Hormones: i.e. hormone structure
a. Protein hormones – effect is on receptors within the membrane, binds
to the receptors on the outside of membrane; its effects are the most rapid of
all the hormones
b. Amine hormones – same relatively fast receptor response as protein
hormones. Examples are catecholamines and thyroid hormones
i. Epinepherine
ii. Norepinepherine
iii. Thyroid hormones
iv. Melatonin
c. Steroid hormones – binds to the intracellular receptors; slow actions
i. Gonadal hormones
1. Estrogen, progesterone, androgens
ii. Adrenal hormones
1. Glucocorticoids, mineralocorticoids
Mechanism of Hormone Action
•
All hormone action is receptor mediated
•
hormone binding to specific receptor results in conformational change
in receptor that conveys a signal to target cell
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Lecture 1 – Biochemistry – Endocrinology – 2nd Class- IBN HIAN Medical college 2016/2017
Types of cell receptors: Another classification of hormones is according to
their
receptor
location
into
two
groups:
Group I: Intracellular Receptors
These
diffuse
through
the
membrane of cells forming HRcomplex inside the cells which
undergo structural changes that
enhance the binding of complex to
DNA of the cell results in gene transcription (mRNA production) which
affects metabolic response. Ex; Steroid and thyroid hormones
Group II: Cell surface receptors
These are protein-derived hormones that are water-soluble compounds so
they cannot diffuse inside the cell but
they bind to surface receptors and the
signals
through
transmitted
the
intracellularly
second
messenger,
(hormone is the first messenger).
Example; Peptide hormones
and catecholamines
This group can be classified according to
their
second
messengers
into
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subgroups:
Subgroup (A) They act by increasing
cAMP level inside the cells through activation of cell membrane enzyme
(adenylate cyclase). Termination of hormonal response occurs by the action of
phosphodiesterase which converts cAMP to 5ʹ-AMP which is inactive. Caffeine
which is Xanthine derivative inhibits phosphodiesterase activity therefore causes
prolonged hormonal action.
Subgroup (B) They act by increasing cGMP level inside the cells through
activation of guanylate cyclase. It includes one hormone only called atrial
natruretic factor (ANF) which is produced by atrial tissue of heart and causes
natruresis, vasodilation and inhibition of aldosterone secretion, therefore;
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Lecture 1 – Biochemistry – Endocrinology – 2nd Class- IBN HIAN Medical college 2016/2017
results in decreased sodium (Na⁺↓ and BP↓). cGMP breaks down by the action
of cGMP phosphodiesterase. Therefore, drugs that activate guanylate cyclase
increase cGMP level, such as Nitroprusside and Adalat (trademark for Nifedipine) are used
in treatment of hypertension.
Subgroup (C) the second messenger is phosphoinositol e.g. ADH, when this
hormone attaches to its receptor on the cell surface, it will activate an enzyme
called phospholipase
C, which acts
to increased calcium ion levels
intracellularly. This ion binds to specific protein called calmodulin, forming
calcium- calmodulin complex, which are similar to cAMP.
Subgroup (D) the second messenger is unknown for hormones including
insulin, GH, prolactin (PRL) and hCG. There is no a definitive messenger for
them but they act almost all over the body.
Endocrine system control (axes and feedback loops):
 Hypothalamic-Pituitary Axes
•
Three main axes involving hypothalamus and pituitary control much of
endocrine system
- operate by negative feedback (Short and long loops)
– Hypothalamic-Pituitary-Thyroid axis (HPT)
– Hypothalamic-Pituitary-Adrenal axis (HPA)
– Hypothalamic-Pituitary-Gonadal axis (HPG)
Mechanisms in Endocrine Axis:The mechanism starts with neural signals which
stimulate the production of releasing hormones (RH)
from the hypothalamus. Each of these RH triggers
its target cell in anterior pituitary gland to produce
its corresponding tropic hormone. These tropic
hormones circulate in blood and act on their target
gland or tissue to produce their response.
Note: prolactin is the exception because its secretion is normally inhibited (RHIH is high). But
when there are tumour e.g. chromope adenoma, or when there is pregnancy and lactation, the
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Lecture 1 – Biochemistry – Endocrinology – 2nd Class- IBN HIAN Medical college 2016/2017
RH of prolactin is dominant, which results in increased level of prolactin in blood (
hyperprolactinemia)
Q: Are all hormones under Axis Control? Give examples?
No, such as calcitonin of thyroid gland and parathyroid hormone that's produced by
parathyroid glands. Both of these hormones are controlled by serum calcium level. Also
Insulin and glucagon are secreted from the pancreas. They are under the control of blood
glucose level.
Q) How many endocrine glands are there in the body, what classes do they fall in?
They are two types:
1. Master glands (hypothalamus and pituitary)
2. Target glands (all the other glands)
Major Endocrine Glands
•
Hypothalamus
•
Anterior pituitary
•
Posterior pituitary
•
Pineal
•
Thyroid
•
Parathyroids
•
Adrenal medulla
•
Adrenal cortex
•
Pancreas
•
Ovaries
•
Testes
•
Placenta
Control Mechanisms:These are mechanisms that maintain normal level of hormones both in serum
and tissues, these are:
 Negative feedback inhibition; it is the commonest type in which
increase in product of axis more than normal level will inhibit the
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Lecture 1 – Biochemistry – Endocrinology – 2nd Class- IBN HIAN Medical college 2016/2017
whole axis activity. For e.g. the hypothalamus-pituitary-adrenal
axis (HPA axis). Any increase its end product level (cortisol) will
inhibit the secretion of hypothalamic hormone which is CRH (for
corticotropin-releasing hormone) and this in turn, will not
stimulate pituitary hormone ACTH (adrenocorticotropin hormone)
any longer. This is called long loop inhibition. While when pituitary
hormones increase, they will inhibit hypothalamus secretion. This
is called short loop inhibition. This mechanism is lost in patients of
Cushing's syndrome in which case cortisol secretion is vast.
 Neural stimulation: physical or emotional stress may result in
neural signals from the brain to hypothalamus and therefore
increase in pituitary hormone secretion as well as the target gland
(axis stimulation). This is called (open loop control system) may
result in clinical findings similar to endocrine diseases.
 Inherited rhythm (circadian rhythm); intermittent release of
hypothalamic or pituitary hormones results in regular daily
secretion of target hormones. Example is cortisol—it is higher at
morning and lower at night. This rhythm is lost in patients of
Cushing's syndrome.
Endocrine Disease:It is of two types:
1. Primary endocrine disease:
Failures of target glands respond to hypothalamic or pituitary hormones, which are
normal. This leading to loss of negative feedback inhibition, therefore there is excessive
production of pituitary hormones
e.g. ovarian failure leading to very low oestrogen, which stimulates the hypothalamic
(GnRH) or pituitary (LH and FSH) secretion.
2. Secondary endocrine disease:
Deficiency of hypothalamus or pituitary hormones that result in deficiency of target
gland hormones as well.
e.g. Damage to hypothalamus causes deficiency of GnRH which causes no stimulation
for pituitary hormone production, i.e. low levels of LH and FSH which leads to no
hormonal action on target tissues (ovaries) that means low levels of serum oestrogen
and progesterone (in female). This example can applied to other systems.
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Lecture 1 – Biochemistry – Endocrinology – 2nd Class- IBN HIAN Medical college 2016/2017
Hypothalamic Hormones:The hypothalamus produces two groups of hormones that are associated with posterior and anterior
pituitary.
The first group includes 3 peptide hormones that travel down to the posterior pituitary through
nerve fibres where they are stored there. These hormones are:
Arginine-vasopressin (or known as ADH): when there is hyperosmolality e.g. dehydration,
this hormone acts on renal tubule through special receptors enhancing water reabsorption
(without salts) from tubules to the blood. This means dilute the blood and corrects osmolality,
but concentrated urine is produced.
The reverse is true, that is to say when the subject drinks a lot of water/fluid, this will
decrease blood osmolality and inhibits ADH secretion, with more loss of water in urine (dilute
urine is produced), so disease or trauma that causes damage of posterior pituitary causes
deficiency of ADH resulting in a syndrome called diabetes insipidus. Also, congenital absence
of tubular receptors of ADH (renal cause), results in a similar syndrome called nephrogenic
diabetes insipidus. Dx by water restriction test or by measuring ADH

Oxytocin: a hormone similar in structure to ADH, controls ejection of milk from
lactating breasts. It also initiates uterine contraction during labour. It can be used in
obstetrics to induce labour, in the form of drugs called Pitocin.

Neurophysin: its function is not clear but it may transport and restore the above two
hormones.
The second group includes tri or tetrapeptide molecules called regulatory hormones that are produced
in the hypothalamus and are transported through blood network to anterior pituitary. These are of 2
types:
1. Releasing hormones (RH)
2. Releasing hormone-inhibitory hormones (RHIH)
The RH stimulates release of anterior pituitary hormones, whilst RHIH inhibits them. Normally, all
pituitary hormones undergo stimulation, except prolactin (PRL), which undergoes inhibitory effect (its
release is normally inhibited).
Classification of Anterior Pituitary Hormones:According to their chemical composition, these hormones are of 2 types:
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Lecture 1 – Biochemistry – Endocrinology – 2nd Class- IBN HIAN Medical college 2016/2017
1. Simple polypeptides: such as GH and prolactin, both of them have no specific target
endocrine tissues, but they act directly to do their effects, e.g. GH enhances bone and cartilage
growth, while prolactin acts on mammary gland (lactation).
2. Glycoproteins: such as LH, FSH, TSH and ACTH. This group is more resistant to heat and
other environmental factor outside the body. (Why?). Because of the presence of carbohydrate
moiety (part) in their structures which make them more resistant to proteolysis and damage.
Hypopituitarism:Defect in secretion of pituitary hormones, which is of two types:
1. Isolated hormonal deficiency: only one or two hormones are deficient while the other
hormones are normal, usually due to congenital abnormalities in hypothalamic centers result in
deficient releasing hormones. The usual hormones affected are gonadotropins and GH.
2. Panhypopituitarism: All hormones of anterior pituitary are deficient due to pituitary tumours
or infarction (loss of blood supply) such as in post-partum haemorrhage (also called Sheehan's
syndrome).
Clinical and biochemical consequences of hypopituitarism:
The features are usually due to target gland failure e.g.

Deficiency of LH or FSH causes secondary hypogonadism, which results in amenorrhea
(absence of menses), infertility, atrophy of secondary sex characters, loss of libido and
impotence in male.

Deficiency of GH and TSH causes growth retardation (dwarfism).

Deficiency of ACTH causes secondary adrenocortical hypo-function. [This type should be
differentiated from the primary type that's called Addison's disease [in which the adrenal gland
itself is destroyed by bacterial infection or by auto-immune disease (auto-antibodies) which
means loss of adrenocortical function (cortisol↓)].
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Lecture 1 – Biochemistry – Endocrinology – 2nd Class- IBN HIAN Medical college 2016/2017
In Addison's disease, there are low levels of cortisol with a very high level of ACTH. In the
secondary type, both of these hormones (cortisol and ACTH) are on low levels. The second
difference
is
that
in
primary,
there
is
hyperpigmentation while in secondary there is
no pigmentation (why?);
because the low level of cortisol in Addison's
results in loss of negative feedback inhibition,
which results in excessive secretion of CRH and
so ACTH. But this latter is also stimulator of
melanocytes (cells
of
melanin)
which
are
important for melanin production that give us
dark
pigmentation
of
skin
and
mucous
membranes.
Out comes: The student should be able to
differentiate
various
functions
of
hypothalamic, posterior and anterior pituitary hormones and capable to use them in
understanding and diagnosing different endocrine disorders.
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