Signalling mechanism of hormones

Dr. Sadaf Mumtaz27-1-11

Broad Classification (Structure)

Hydrophillic Lipophillic

Proteins, peptide hormones & catecholamines

Steroid and thyroid hormones

Primarily act through second messenger system

Activate genes on binding with receptors in the nucleus

Circulate mainly dissolved in the plasma

Largely bound to plasma proteins

Synthesis of hormones• Polypeptides and protein hormones ---- Size 3AA to 200AA

Steroid hormones• Cholesterol esters stored in cytoplasmic vacuoles can be mobilized

for steroid synthesis

Location for different types of hormone receptors

Amine Hormones

• Formed by the action of enzymes in the cytoplasmic compartment of glandular cells

• Thyroid gland

• Epinephrine and nor epinephrine

Thyroglobulin Thyroxine binding

globulin

Plasma

• What are trophic hormones– A hormone that has its primary function the regulation of

hormone secretion by another endocrine gland

• What is – Permissiveness

• One hormone must be present in adequate amounts for the full exertion of another hormone’s effect.

– Synergism• The combined effect is greater then the sum of the separate effects.

– Antagonism• When one hormone causes the loss of another hormone’s

receptors, reducing the effectiveness of the second hormone

Onset of hormone secretion and action

Feedback control of hormone secretion

• Negative feedback– Through hormone or one of its product– Controlled variable

• Positive feedback

Cyclic variations

Mechanism of activation of GPCRs

Enzyme linked hormone receptors

Second messenger mechanisms

ER

SOCTRPC1,4

IP3R

RhoA-GTP

RhoGDI-P

Rhokinase

MLC-P

ROCTRPC3,6,7

Ca2+

calmodulin

Ca2+CaM

CamKinase II

Inactive MLCK

ActiveMLCK

Phosphorylation

MLC

Dephosphorylation

MLCP

Inactive Phosphorylated MLCP (PP1c-MYPT1)

GPCRRTK

Agonist

PLC

PIP2

DAGIP3

Ca2+

PKC

Ca2+

CP1-17 CP1-17-P

PP2A

MT dissassembly

Actin polymerization

Stress fibre formation

Activation mechanism of ECs

MLCP

Measurement of hormone concentration in the Blood

• Radioimmunoassay

• Enzyme linked immunosorbent assay (ELISA)

Radioisotope Antibody Hormone

Enzyme Antibody Hormone

Radioimmunoassay

Antibody

Fluid from animal containing hormone

+ +(Hormone + Radioisotope)

Competition for antibody binding

Equilibrium

Antibody complex separated

Quantity of radioactive hormone complex is measured by radioactive counting technique

ELISA

Hormones

• a) are secreted by exocrine glands.

• b) act only on neighboring cells.

• c) are always peptides.

• d) are secreted into the blood.

Hormone receptors:

• a) have a high affinity for their natural ligand.

• b) are always linked to G proteins.

• c) are lipids.

• d) are always located in the plasma membrane of their target cells

G protein activation:

• a) leads to changes in gene expression.

• b) always causes an increase in cyclic AMP.

• c) leads to the generation of second messengers.

• d) always results in a decrease in cyclic AMP

Steroid hormones such as aldosterone:

• a) bind to nuclear receptors to regulate gene expression.

• b) activate G protein cascades.

• c) activate receptors on the cell membrane.

• d) directly regulate protein synthesis

Pituitary hormones and its control by hypothalamus

Hypothalamic releasing and inhibiting hormones control anterior pituitary secretion

TRH

GnRH

CRH

GHRH

GHIH

PIH

• If the pituitary gland is removed from its normal position beneath hypothalamus and transplanted to some other part of the body– What will happen to its rate of secretion of

different hormones?

Thank you