Post on 18-Jan-2016
Assist prof. of Medical Physiology
• To do its action, the hormone must bind to specific
molecules on the cells called receptors.
• Hormone receptors are 2 types according to its location;
Cell surface or cell membrane receptors
Intracellular receptors
– Water soluble hormones e.g. peptide hormones,
catecholamines bind to cell membrane receptors
on the surface of target cells
1. Activation of a membrane-bound enzyme.
2. Rise of intracellular Ca++ concentration:
3. Increase in cell membrane permeability to
Na+, K+ and Cl-.
• Membrane-bound enzymes include adenyl cyclase
• Activation of this enzyme generates a intracellular 2nd messenger (e.g. cyclic AMP) → biological response
• The hormone-sensitive adenyl cyclase system
has 3 components:
i) The receptor:, stimulatory or inhibitory (Rs or
Ri).
ii) G protein: guanine nucleotide (GTP) – binding
protein (Gs or Gi).
iii) Catalytic component (C): enzymatically
converts Mg2+-ATP to cyclic AMP.
1. Receptors 1. Receptors
2. G 2. G protein protein
3. Catalytic 3. Catalytic subunit subunit
• It is a guanine nucleotide – binding protein • It may be Gs or Gi
a) Gs mediate the action of the hormones that
stimulate adenylyl cyclase activity,
b) Gi mediates the action of hormones that
inhibit adenylyl cyclase activity.
• Gs and Gi are heterotrimers comprised of a unique
-subunit (s or i) and similar and subunits.
βγ
Catalytic subunit
G protein
ATP
C-AMP
Activate enzymes
α
Adenyl-cyclase systemReceptor
Binding of the hormone to the receptor
activate G-proteins
dissociate the α-subunit
change the activity of membrane-bound enzyme
"second messenger
mediate the action of the hormone
– This occurs by 2 mechanisms:
i- Increase Ca++ influx,
– by activating ligend gated Ca++ receptors.
ii- Release of Ca++ from
– endoplasmic reticulum,
– mitochondrial membrane.
• ↑ free cytosolic Ca++ produce the following:
1. Changes in cell motility
2. Contraction of ms cells.
3. ↑ed release of secretory proteins.
4. Activation of regulatory enzymes.
5. Ca++ binds to specific calcium – binding proteins, such
as;
Calmodulin in smooth ms
Troponin C in skeletal ms
• Binding of hormone to its membrane receptors
↑es membrane permeability to Na+, K+ and Cl-.
Cytoplasmic Cytoplasmic Receptors Receptors
Nuclear Receptors Nuclear Receptors
Steroid HormonesSteroid Hormonese.g. vit D and e.g. vit D and
retinoids retinoids
Thyroid Hormones Thyroid Hormones
Mechanisms of interaction of lipophilic hormones, such as steroids and thyroid
– It is a secretion released by a nerve cell &
reaches the endocrine glands via blood vessels
or nerve fibres.
Example
1.Hypothalamic releasing & inhibitory hormones
is an example of this type of control
2.Post pituitary hormones are released from
terminals of the hypothalamohypophyseal tract.
Hypothalamic releasing and inhibitory
hormones
Posterior pituitary hormones
•Usually done by autonomic fibres e.g. sympathetic control of the adrenal medulla
Negative Feedback Negative Feedback Positive Feedback Positive Feedback
Most common Most common Less common Less common
Trophic Gland
Target Gland
A+ +
B
_ _
Hypothalamus
Pituitary g.
Adrenal cortex
CRH
ACTH
Glucocorticoids
--
--
Significance:
1.Prevent overstimulation of the target glands by
the tropic hormones.
2.Adjust the rate of hormone secretion according
to the body needs.
3.Maintain hormone blood level relatively constant.
Trophic Gland
Target Gland
A+ +
B
+ +
• Less common
• When a target gland hormone (B) is increased, it
will increase the rate of secretion of its pituitary
tropic & hypothalamic releasing hormones (A)
• This relation increases the target gland hormone
more and more.
• When the target gland hormone reaches sufficient
level negative feedback returns again to reduce
the hormone to its final level.
Hypothalamus
Pituitary g.
ovary
Gn-RH
LH
Estrogens
++
++
LH surgeEssential
for ovulation
LH surgeEssential
for ovulation
Significance:
– Temporary amplification of the biological
effects of the hormone.
Example:
– The link between estrogen and LH
– Pre-ovulatory LH surge.
Feed-back control system may be:
A) Long loop feed-back:
– Represents the relationship of target gland H
and their ant pituitary trophic hormones.
B) Short loop feed-back:
– Relation between ant pituitary trophic H and the
hypothalamic releasing and release-inhibiting H.
Hypothalamus
Pituitary G.
TRH+ +
TSH
--
Thyroid G.+ +
T3 and T4
Long Loop
--
Short Loop
a) Organic substances e.g.
Blood glucose level and the secretion of pancreatic H.
b) Inorganic substances e.g. blood Ca+2, Na+,K+.
Blood Ca+2 level and parathyroid and calcitonin
hormones.
Blood Na & K level and aldosterone.
Plasma inorganic substances determines the blood
osmolarity, that affect the hypothalamic release of
ADH.
Def:
• Cytokines are small proteins produced by various
cell types in different physiological and pathological
states.
• Cytokines modulate endocrine functions by acting on:
•the endocrine glands and
•on the target tissues.
Example:
– Cytokine hormones (e.g., leptin) produced by
adipocytes also called adipokines.
– Leptin
•suppresses GH through stimulation of
somatostatin,
•suppresses gonadotropins and
•stimulates the pituitary–adrenal axis.