Assist prof. of Medical Physiology. To do its action, the hormone must bind to specific molecules on the cells called receptors.

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.