Transcript Introduction 2

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.
3. Catalytic subunit
1. Receptors
2. G protein
• 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.
Adenyl-cyclase system
Catalytic subunit
Receptor
G protein
γ β
C-AMP
Activate enzymes
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 Receptors
Steroid Hormones
e.g. vit D and retinoids
Nuclear Receptors
Thyroid Hormones
Mechanisms of interaction of lipophilic hormones, such as
steroids and thyroid
1. Neural control or neurosecretion
2.Direct innervation
3.Feedback control
4.Blood Level of substances
5.Cytokines
– 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
Most common
Positive Feedback
Less common
Trophic
Gland
A
++
Target
Gland
B
__
-
Hypothalamus
CRH
Pituitary g.
ACTH
Adrenal cortex
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
A
++
Target
Gland
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
Gn-RH
Pituitary g.
+
LH surge
Essential
for
ovulation
LH
ovary
Estrogens
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
-
Short Loop
TRH
++
Pituitary G.
TSH
++
Thyroid G.
T3 and T4
Long 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.