Mechanism of action of

hormones acting on cell surface

ByDr. Umar M.T

OUTLINE• Introduction• Hormones that act on cell membrane receptors• Structure of cell membrane receptors• Types of cell membrane receptors•Mechanisms of action• Clinical relevance• Conclusion

Introduction

• Hormones can be defined as chemical signals secreted into the blood

stream that act on distant tissues, usually in regulatory fashion

• To respond to a hormone, a target cell must contain the essential components of a signaling pathway

• Hormone binds to receptor resulting in an appropriate downstream signaling pathways that leads to physiologic responses

Hormones that act on cell membrane receptors

• They include polypeptide hormones, monoamines and Prostaglandins• They hydrophilic in nature• Can not cross cell membrane• As such need a 2nd messenger to carry out their effect inside cell• Examples Insulin GH Catecholamines Prolactin etc

Structure of cell membrane receptors

• Cell surface receptors are integral membrane proteins• They have three regions/domains

1. Extracellular domain2. Transmembrane domain3. Intracellular domain

Structure of cell membrane receptors cont’d• Extracellular domains: Hydrophilic Ligand binding domain Locate outside cell surface Binds to 1st messenger/hormone• Transmembrane domains: Located within cell membrane Hydrophobic Anchors the receptor

Structure of cell membrane receptors cont’d• Intracellular domains:• Cytoplasmic domain• Tail of receptor• Interacts with molecules leading to generation of second messenger

Membrane receptor types1. Single pass protein receptor e.g Growth factor receptor

2. Multiple subunits receptor e.g Insulin receptor

3. Serpentine receptor e.g Adrenergic receptor

Membrane receptor types cont’d

Receptor-couple activity• Ion channel- linked receptor

• Enzyme linked receptor

• G-protein- couple recptor

Mechanisms of action

• Signal transduction.• Binding of hormone (1st messenger) to receptor initiates a series of

events • This leads to generation of 2nd messengers within the cell

• The second messengers then trigger a series of molecular interactions that alter the physiologic state of the cell.

• 1st messenger→ Receptor→ 2nd messenger→ Physiologic effect

2nd messengers & associated hormones

Second Messenger Examples of Hormones Which Utilize This System

Cyclic AMP Catecholamine, Glucagon, LH, FSH, TSH, Calcitonin, PTH, ADH

Protein kinase activity Insulin, GH, Prolactin, Oxytocin, Erythropoietin, Growth factors

Calcium and/or phosphoinositides Catecholamine, Angiotensin II, ADH, GnRH, TSH.

Cyclic GMP ANP, NO

Cyclic AMP Second Messenger Systems

• Hormone binds to receptor through a set of G proteins which activate adenylate cyclase in the cell membrane.

• Activated adenylate cyclase convert ATP to cAMP, resulting in ↑cAMP

• ↑cAMP in the cytosol activate protein kinase A

• Activated protein kinase A phosphorilate to other enzymes leading to physiologic activity

• The process is deactivated by Phosphodiesterase which↓ cAMP

Tyrosine Kinase Second Messenger Systems• The hormone binds to receptor domains exposed on the cell surface

• Resulting in a conformational change leading to auto phosphorylation of the receptor

• The activated receptor phosphorylates a variety of intracellular enzymes leading to physiologic events.

Insulin receptor

Calcium ion channels messenger systems

Clinical relevance1. Some receptor defects are associated with endocrine disorders

2. Some medications act via cell receptors

3. Some cancers are associated with receptors that continually stimulate second messengers

Diseases Caused by G Protein–Coupled Mutations

• Familial male precocious puberty• Familial non-autoimmune hyperthyroidism• Familial hypocalcemic hypercalciuria

• Nephrogenic DI• Familial ACTH resistance • Familial GH deficiency • Hypogonadotropic hypogonadism

Conclusion • Understanding the mechanism of hormone action is very important in

treating some medical disorders • It encompasses knowing the structure and function of a receptor

• How the hormone bind to receptor and transduces a signal to effectors inside cells.

THANKS

NAGODE