OVERVIEW ENDOCRINE SYSTEM Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College ENDO BLOCK 412

OVERVIEW ENDOCRINE SYSTEM

Dr. Shaikh Mujeeb AhmedAssistant ProfessorAlMaarefa College

ENDO BLOCK 412

Objectives

• Understanding the common aspects of neural and endocrinal regulations.

• Describing the chemical nature of hormones• Recalling the overall hormonal functions• Understanding the different mechanisms of

hormonal action & concept of second messenger system

Objectives

• Understanding the common aspects of neural and endocrinal regulations.

• Describing the chemical nature of hormones• Recalling the overall hormonal functions• Understanding the different mechanisms of

hormonal action & concept of second messenger system

Introduction

• Body systems always works to maintain homeostasis

• Two major regulatory systems of body are– Nervous system– Endocrine system

Nervous and Endocrine Systems

• Act together to coordinate functions of all body systems• Nervous system

– Nerve impulses/ Neurotransmitters– Faster responses, briefer effects, acts on specific target

• Endocrine system– Hormone – mediator molecule released in 1 part of the body

but regulates activity of cells in other parts– Slower responses, effects last longer, broader influence

Fig. 13.2

Comparison between Nervous and Endocrine system

Nervous system

• The nervous system exerts point-to-point control through nerves, similar to sending messages by intercom. Nervous control is electrical in nature and fast.

Hormones travel via the bloodstream to target cells

•The endocrine system broadcasts its hormonal messages to essentially all cells by secretion into blood and extracellular fluid. Like a radio broadcast, it requires a receiver to get the message - in the case of endocrine messages, cells must bear a receptor for the hormone being broadcast in order to respond.

General Principles of Endocrinology

• The endocrine system consists of the ductless endocrine glands that are scattered throughout the body.

• The endocrine glands are not connected anatomically• They constitute a system in a functional sense. • Secreting hormones into the blood• Once secreted, a hormone travels in the blood to its distant

target cells, where it regulates or directs a particular function.

• Endocrinology is the study of the homeostatic chemical adjustments and other activities that hormones accomplish.

A cell is a target because is has a specific receptor for the hormone

Most hormones circulate in blood, coming into contact with essentially all cells. However, a given hormone usually affects only a limited number of cells, which are called target cells. A target cell responds to a hormone because it bears receptors for the hormone.

Hormone receptors

Types of Hormone

• According to the distance the hormone travel– Endocrine– Paracrine– Autocrine– Intracrine

• According to solubility– Hydrophilic eg. Peptide, hormone– Lipophilic eg. Steroid & thyroid hormone

Types of Hormone

Hormone types

– Circulating – circulate in blood throughout body

– Local hormones – act locally

• Paracrine – act on neighboring cells

• Autocrine – act on the same cell that secreted them

Characteristics of Peptide hormone• Produced and processed by the endoplasmic reticulum and Golgi complex of

the endocrine cell• Stored in secretory vesicles until signaled for release by exocytosis. • Circulate in the blood largely dissolved in the plasma• Bind with surface membrane receptors of their target cells, • Act primarily through second-messenger pathways to alter the activity of

preexisting proteins, such as enzymes, to produce their physiologic response.

• The peptide molecule prepared first is usually a larger precursor called as Preprohormone; It is cleaved to form Prohormone; further cleavage of Prohormone, forms the final mature Hormone.

Example: Preproinsulin → Proinsulin → Insulin

This hormone is stored in vesicles of endocrine cells and released on demand

Water-solublehormone

Receptor

G protein

Blood capillary

Binding of hormone (first messenger)to its receptor activates G protein,which activates adenylate cyclase

Adenylate cyclase

Target cell

1


Receptor

G protein

cAMP

Second messenger

Activated adenylatecyclase convertsATP to cAMP

Blood capillary


Adenylate cyclase

Target cell

ATP

1

2


Receptor

cAMP serves as asecond messengerto activate proteinkinases

G protein

Protein kinases

cAMP

Second messenger


Blood capillary


Adenylate cyclase

Target cell

ATP

1

2

3 Activatedproteinkinases


Receptor


G protein

Protein kinases

cAMP

Activatedproteinkinases

Second messenger


Activated proteinkinasesphosphorylatecellular proteins

Blood capillary


Adenylate cyclase

Target cell

ATP

1

2

4

3

Protein— P

ADP

Protein

ATP


Receptor


G protein

Protein kinases

cAMP


Protein—

Second messenger



Millions of phosphorylatedproteins cause reactions thatproduce physiological responses

Blood capillary


Adenylate cyclase

Target cell

P

ADP

Protein

ATP

ATP

1

2

4

3

5


Receptor


G protein

Protein kinases

cAMP


Protein—

Second messenger

Phosphodiesteraseinactivates cAMP



Millions of phosphorylatedproteins cause reactions thatproduce physiological responses

Blood capillary


Adenylate cyclase

Target cell

P

ADP

Protein

ATP

ATP

1

2

6

4

3

5

Characteristics of lipophilic Steroid hormone

• By stepwise modifications of a basic cholesterol precursor molecule.

• Steroidogenic (“steroid-producing”) organs specialize in the type of hormones they produce because each of these organs has the enzymes necessary to produce only one or several, not all, of the steroid hormones.

• Steroid hormones act primarily by activating genes on binding with receptors inside the cell, thus bringing about formation of new proteins in the target cell that carry out the desired response.

• lipophilic hormones are largely bound to plasma proteins.

1 Lipid-solublehormonediffuses into cell

Blood capillary

Target cell

Transportprotein

Free hormone


Blood capillary

Activatedreceptor-hormonecomplex altersgene expression

NucleusReceptor

mRNA

DNACytosol

Target cell

Transportprotein

Free hormone

2


Blood capillary


NucleusReceptor

mRNANewly formedmRNA directssynthesis ofspecific proteinson ribosomes

DNACytosol

Target cell

Transportprotein

Free hormone

Ribosome

2

3


Blood capillary


NucleusReceptor

mRNANewly formedmRNA directssynthesis ofspecific proteinson ribosomes

DNACytosol

Target cell

New proteins altercell's activity

Transportprotein

Free hormone

Ribosome

Newprotein

2

3

4

Characteristics of lipophilic thyroid hormone

• synthesized by a unique pathway within the thyroid gland but functions at its target cells by means similar to those used by lipophilic steroids.

OVERALL FUNCTIONS OF THE ENDOCRINE SYSTEM

1. Regulating organic metabolism and H2O and electrolyte balance

2. Inducing adaptive changes to help the body cope with stressful situations

3. Promoting smooth, sequential growth and development

4. Controlling reproduction 5. Regulating red blood cell production6. Along with the autonomic nervous system,

controlling and integrating activities of both the circulatory and digestive systems

TROPIC HORMONES

• A hormone that has as its primary function the regulation of hormone secretion by another endocrine gland is classified functionally as a tropic hormone (tropic means “nourishing”).

• Example: Thyroid stimulating hormone (TSH), Adrenocorticotropic hormone (ACTH) etc.

COMPLEXITY OF ENDOCRINE FUNCTION

1. A single endocrine gland may produce multiple hormones n(Anterior Pituitary).

2. A single hormone may be secreted by more than one endocrine gland. For example, both the hypothalamus and pancreas secrete the hormone somatostatin.

3. Frequently, a single hormone has more than one type of target cells (Vasopressin)

4. The rate of secretion of some hormones varies considerably over the course of time in a cyclic pattern.

5. A single target cell may be influenced by more than one hormone.

Cont..

6. The same chemical messenger may be either a hormone or a neurotransmitter

7. Some organs are exclusively endocrine in function (they specialize in hormone secretion alone, the anterior pituitary being an example), whereas other organs of the endocrine system perform non endocrine functions in addition to secreting hormones (the testes).

Mechanisms of Hormone Action• Response depends on both hormone and

target cell• Lipid-soluble hormones bind to receptors

inside target cells• Water-soluble hormones bind to receptors on

the plasma membrane– Activates second messenger system– Amplification of original small signal

Cell mechanism & Second messengers• G Protein–Linked Hormone Receptors.

– Many hormones activate receptors that indirectly regulate the activity of target proteins (e.g., enzymes or ion channels) by coupling with groups of cell membrane proteins called heterotrimeric GTP-binding proteins (G proteins)

Second messengers for cell-surface receptors

Second messenger systems include: Adenylate cyclase which catalyzes the conversion of ATP to

cyclic AMP; Guanylate cyclase which catalyzes the conversion of GMP

to cyclic GMP (cyclic AMP and cyclic GMP are known collectively as cyclic nucleotides);

Calcium and calmodulin; phospholipase C which catalyzes phosphoinositide turnover producing inositol phosphates and diacyl glycerol.

Adenyl Cyclase–cAMP SecondMessenger System

• Hormone binds to the receptor

• GDP is released from G protein

• Activate adenyl cyclase which convert ATP to cAMP

• cAMP activates tyrosine kinase A

• Tyrosine kinase A phosphorylate specific protein for physiological action

IP3 Mechanism

• Hormone binds to the receptor

• Phospholipase C liberates DAG & IP3

• IP3 mobilizes Ca++ from ER• Ca++ and DAG activates

tyrosine kinase C• Tyrosine kinase C

phosphorylate specific protein for physiological action

Calcium-Calmodulin SecondMessenger System

• Hormone binds to the receptor• Open Ca++ channels & release Ca++ from ER• Ca++ binds to calmodulin to produce

physiological action

Table 18-3, p. 674

Sequence of Steroid hormone action

Summary of Chemical Structure, Synthesis, and Transport of Hormones

Properties Peptides Catechol-amines ThyroidHormone

Steroids

Synthesis and storage

Polyribosomes -ER as preprohormones/ Vesicles

Cytosol/ ATP Ca++ / Chromagranin Vesicles

Colloid of follicular cells pendrin (iodide/chloridetransporter

Mitochondria/ cytosol

Release from parent cell

Exocytosis Exocytosis thyroglobulin to megalin endocytosis/ lysosomal degradation

diffusion

Transport in blood

Most are free Loosely bound to albumin

TBG, transthyretin, albumin

Albuminsex hormone or sex hormone or corticosteroid BG

Half life Minutes 1-2 Minutes T4- 7days, T3- 18 days hours

Location of receptor

plasma membrane plasma membrane

intracellular intracellular

Response to receptor-ligand

binding

protein phosphorylation genomic

protein phosphorylation genomic

genomic genomic

35

References

Human physiology, Lauralee Sherwood, seventh edition.

Text book physiology by Guyton &Hall,11th edition.

Physiology by Berne and Levy, sixth edition.

Documents

OVERVIEW ENDOCRINE SYSTEM Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College ENDO BLOCK 412