Introduction to the Endocrine System

Endocrine Glands: (Ductless Glands)

Glands with NO ducts that secrete hormones directly into blood → affect target cells in certain tissues
& organs all over the body {pituitary, thyroid, parathyroid, adrenal (suprarenal), pineal glands,
pancreas, testis & ovaries}.

Definition of Hormones:
Specific chemical substances that secreted by special endocrine cells into blood to affect nearby or
distant target cells (i.e. chemical messengers).

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Nature of Hormones:
1) Polypeptides (Proteins): Hypothalamic, Pituitary, Pancreatic hormones, Parathormone,
Calcitonin and GIT hormones.
2) Steroid: Suprarenal cortical hormones, Gonadal (sex) hormones & Vit. D derivatives.
3) Tyrosine derivatives: Thyroid hormones & catecholamines (suprarenal medullary hormones:
adrenaline, noradrenaline & dopamine).

Target Cells & Tissues of Different Hormones:

 Some hormones affect many different types of cells all over the body:
e.g. Growth hormone (GH) & Thyroid hormones.
Such hormones are very important in regulation of almost all body functions (growth &
development, metabolism, reproduction ......etc)

 Other hormones affect only specific target tissues:

e.g. Thyroid stimulating hormone (TSH) → acts on thyroid gland.
Ovarian hormones (Estrogen & Progesterone) → act on female sex organs & secondary sex
characters.

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 Forms of Hormone in Plasma
Free Form Bound to protein
Free in plasma, Not carried on plasma carried on plasma proteins.
protein.
Active (can bind to receptors). Non active (can not bind to receptors).
Small in size (MW), can be filtered by Large in size (MW), can not be filtered in urine.
kidney into urine.
Has short half-life duration. Relatively has long half-life duration.
Peptides & catecholamines hormones Steroid & thyroid hormones (water insoluble
(water soluble hormones): are transported hormones): are transported in blood mainly bound to
free (dissolved) in plasma. plasma proteins & less than 10% is free in plasma.

Classification of Feedback Control of Hormone Secretion

II- According to the distance (between the site of
I- According to the type
hormone secretion & the site of feedback effect)
1) Negative feedback: (the most common type) 1) Long loop feedback:
↓ Hormone level in blood → stimulates its The hormone secreted from an endocrine gland
gland to ↑ the rate of its secretion & vice versa. affects the anterior pituitary & hypothalamus.
Example: 2) Short loop feedback:
↓ T3 & T4 → ↑TSH & vice versa. The hormone secreted from anterior pituitary
2) Positive feedback: (less common type) affects hypothalamus.
↑ Hormone level in blood → stimulates its 3) Ultra-short loop feedback:
gland to ↑ the rate of its secretion. The hormone secreted from anterior pituitary
Example: affects itself (autocrine effect).
↑ estrogen level in blood → ↑ LH (LH surge
th
during the midcycle= 13 day) → ↑ estrogen
secretion.

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The Receptors:
Hormones act on specific target cells & produce their effects through the binding of the
hormone to its specific receptors on the cell membrane, inside the cytoplasm or the nucleus.

Characters of cell receptors:

1) Specific: the hormone binds specifically to its receptor.
2) Dynamic: the number of receptors can be ↑ or ↓ according to metabolic needs.

Down regulation Up regulation

Prolonged exposure to high hormone Prolonged exposure to low hormone
levels leads to: levels leads to:
Definition
1) ↓ Number of cell receptors. 1) ↑ Number of cell receptors.
2) ↓ Cell response to the hormone. 2) ↑ Cell response to the hormone.
1) Internalization: (receptor mediated
endocytosis). 1) ↓ Rate of internalization.
Mechanism
2) ↓ Receptor sensitivity to hormone: 2) ↑ Receptor sensitivity to hormone.
(Desensitization).

Mechanisms of Hormone Action

Binding of the hormone to its specific receptor → hormone - receptor complex → acts by one
of the following mechanisms:
1) Genomic action: transcription of DNA (genetic material) → mRNA → translation in
ribosome → formation of new proteins (may be enzymes or channels).
2) Non- genomic action: No DNA transcription, But activation of cellular enzymes or
cytoplasmic mechanisms.
3) Combined genomic & non-genomic actions.
N.B:
Genomic action is slow as it stimulates protein synthesis (formation of new proteins in the cell).
Non- genomic action is rapid as it activates already present enzymes.

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 1) Genomic action
 The hormones acting by this mechanism are the lipophilic (lipid soluble) hormones:
1) Steroid hormones: Adrenal cortical hormones, Gonadal (sex) hormones & Vit. D
derivatives.
2) Thyroid hormones: T3 & T4.

 The receptors of these hormones are present in the cytoplasm then translocated inside
the nucleus or already present in the nucleus.
 The receptor is composed of several domains e.g: ligand binding domain (LBD) & DNA
binding domain (DBD).
 The hormone binds to its specific receptor → hormone-receptor complex → recognizes
specific target genes → formation of mRNA that diffuses outside the nucleus to
ribosomes → translation & formation of new proteins in the cell (new enzymes or
channels).

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Genomic action of Hormones

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 2) Non-genomic action
 Binding of the hormone (1st messenger) to a surface membrane receptor → hormone-
receptor complex → activation of another intracellular chemical messenger (2nd
messenger) to do the intracellular effects of the hormone at the level of the cell because
the hormone can't cross the cell membrane.
 The hormones acting by this mechanism are the lipophobic (lipid insoluble = water
soluble) hormones as: protein in nature hormones & catecholamines.
 Intracellular signaling after hormone-receptor binding: (Signal transduction)
I) G- protein coupled receptors: (The 2nd messenger is not attached to
receptor)
G-protein is a nucleotide GTP regulatory protein (large hetero-tri-mecic composed
of α, β, ɣ subunits).
When the hormone (ligand) binds to the receptor → the α subunit:
a) dissociates from β, ɣ subunits.
b) Releases GDP & binds GTP.
c) Initiating the cellular effects.
When the hormone is removed from the receptor → the α subunit becomes
inactivated by its inherent GTPase activity that converts GTP to GDP, then α
subunit re-binds to β- ɣ subunits.

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II) Enzyme coupled receptors:
Some receptors when activated, its cellular part acts directly as enzymes or activates a
nearby enzymes.
The main mechanisms of non-genomic actions act through the following 2nd
messengers:
1) Adenyl cyclase- cAMP:
a) Binding of the hormone to the stimulatory receptor → activation of Gs protein.
b) Dissociation of α subunit of Gs protein from β- ɣ subunits.
c) α subunit activates adenyl cyclase (the catalytic unit) → formation of cAMP
(second messenger).
d) cAMP activates protein kinase A (PKA) → initiating many cellular effects.
 Major fraction of PKA → phosphoproteins → many cytoplasmic effects.
 Minor fraction of PKA → translocation into the nucleus → initiating & ↑ rate
of transcription.
e) Limitation of actions of cAMP by phosphodiesterase enzyme (PDE), which
converts cAMP to 5`AMP.
Hormone using this 2nd messenger as: ACTH, parathormone, TSH,
glucagon, LH & angiotensin II.

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 2) Inositol triphosphate & diacylglycerol (IP3 & DAG):
a) Binding of the hormone to the membrane receptor → activation of Gq
protein.
b) Dissociation of α subunit of Gs protein from β- ɣ subunits.
c) α subunit activates phospholipase C enzyme (PLC) → acting on the
membrane phospholipid {phosphatidylinositol 4,5 diphosphate (PIP2)}
splitting it into:
 Inisitol triphosphate (IP3): it is a small sugar that diffuses to the
endoplasmic reticulum, where it binds to IP3 receptors causing the
2+ 2+
release of Ca through the ligand gated Ca channels into cytoplasm
 Diacylglycerol (DAG): is also a second messenger, it stays in the cell
membrane activating protein kinase C (PKC) → phosphoproteins.
Hormone using this 2nd messenger as: TRH & ADH.

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 3) Calcium – calmodulin complex:
2+ 2+
Hormones bind to the receptors → Ca entry → Ca bind with calmodulin →
2+ nd
Ca - calmodulin complex (2 messenger) → activation or inhibition of
intracellular enzymes.

4) Guanylyl cyclase - cGMP:

Hormone using this 2nd messenger as: atrial natriuretic peptide (ANP).

3) Combined genomic & non genomic action

 Some hormones can produces rapid (non-genomic) & slow (genomic) responses as: GH &
Prolactin.

Reference:
 Ganong's Review of Medical Physiology, 23rd edition, p: 50-57.

Best Wishes
Dr. Ahmed Abd Eltawab

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