introduction body functions are regulated by 2 major control systems: 1. nervous system: 2....

IntroductionIntroduction Body functions are regulated

by 2 major control systems:

1. Nervous system: 2. Hormonal, or endocrine system:

• Exerts point-to-point control through nerves.

• Nervous control is electrical in nature.

• It is fast.

Endocrine systemEndocrine system A group of glands which have NO

ducts.

Secrete their hormones into blood & extracellular fluid.

Most hormones circulate in blood, & come in contact with essentially all cells.

Endocrine system Endocrine system … (continued)

A given hormone usually affects only a limited number of cells, called target cells.

Target cell responds in specific way to a hormone as it bears specific receptor proteins for

the hormone.

Hormonal InteractionsHormonal Interactions Synergistic:

Two hormones work together to produce a result.

Additive: Each hormone separately produces response,

together at same concentrations stimulate even greater effect.

NE and Epi.

Complementary: Each hormone stimulates different step in the

process. FSH and testosterone.

Endocrine system Endocrine system … (continued)

Distance between hormone producer cell & hormone responder cell may be large, moderate, or small.

Generally, act slower in onset, more prolonged, & more diffuse than NS.

Under control of NS.

Principal functions of the Principal functions of the endocrine systemendocrine system Maintenance of internal environment

(homeostasis).

Regulation total body metabolism.

Control of energy production, utilization & storage.

Integration & regulation of growth & development.

Control, & maintenance of sexual reproduction, including gametogenesis, fertilization, fetal growth & development & nourishment of the newborn.

body’s response to environmental stimuli.

Important endocrine glands & organsImportant endocrine glands & organs Pituitary gland

(anterior & posterior)

Thyroid gland

Parathyroid gland

Adrenal gland (cortex & medullae)

Islets of Langerhans in Pancreas

Ovaries

Testes

Placenta

Endocrine glands Endocrine glands … (continued)

Hormones & hormone-like substances are also produced by other organs in the body that serve other functions as well; such as:

Heart Atrial natriuretic peptide (ANP) Liver Somatomedins (insulin-like growth

factors IGF-1) Adipose tissue Leptin kidneys Erythropoietin

Hormones?Hormones? A hormone is a chemical

substance that is secreted into the blood by one cell or a group of cells & exerts a physiological control & regulatory effect on other cells of body.

Onset & effect of hormone secretionOnset & effect of hormone secretion Each hormone has its own onset &

duration of action; e.g.

Catecholamine: secreted in sec, & its full action (sec - min.)

Aldosterone: ? takes 1hr to act.

Thyroxine; GH: ? require months for full effect.

Types of hormones:Types of hormones:I: According to site of action

3 types

1) Local hormones

2) General hormones

3) Target tissues hormonese.g.

- Ach- Secretin- Cholecytokinin

e.g.

- Catecholamines

- GH

- TH

e.g.

- ACTH

- Ovarian hormones

- Oxytocin

Types of hormones:Types of hormones: II: According to Chemical classification

Hormones are categorized into 4 structural groups, with members of each group having many properties in common:

Peptides and proteins Amino acid derivatives Steroids Fatty acid derivatives - Eicosanoids

All protein hormones are synthesized in granular ER.

secretory vesicles or

secretory granules

specific signal

Nu

cleu

s D

NA

mR

NA

Cytoplasm

granular ER

Preprohormone

prohormone

Cleaved

Cleaved

final active hormone

Golgi apparatus

1. Peptide/protein hormones1. Peptide/protein hormones

2. Amine hormones2. Amine hormones

AA derivatives hormones are formed by enzymatic action in cytoplasm of glandular cells.

Adrenal medullary hormones are secreted like peptide hormones.

Thyroid hormones, 1st formed as large protein molecule called thyroglobulin, then stored in large follicles in thyroid gland. When to be secreted, cleaved by specific enzyme systems where THs will be released & secreted into the blood.

3. Steroid hormones3. Steroid hormones

All derived from Cholesterol.

Freely permeable to membranes (lipid soluble), so they are not stored in cells & immediately released.

Enzymes that produce steroid hormones from cholesterol are located in mitochondria & smooth ER.

4. Fatty Acid Derivatives – 4. Fatty Acid Derivatives – Eicosanoids Eicosanoids

Are a large group of molecules derived from polyunsaturated fatty acids.

Principal groups of hormones of this class are prostaglandins, prostacyclins, leukotrienes & thromboxanes.

These hormones are rapidly inactivated by being metabolized, & are typically active for only a few seconds.

Arachadonic acid is the most abundant precursor for these hormones which is stored in membrane lipids & released through the action of various lipases.

Stimuli for hormone secretionStimuli for hormone secretion Can be:

1) Chemical, e.g. glucose insulin.

2) Neural, e.g. Ach stimulates the release of Epi & NE from the adrenal medulla.

3) Hormonal, e.g. ACTH adrenal cortex cortisol.

Hormones share special characteristics:Hormones share special characteristics:

1. Found in small concentrations in blood. …(pgm/ml; µgm/ml)

2. Rates of secretion are extremely small, which is controlled by negative feedback effect from target organ to the secretary gland.

3. Has specific receptors in target organ.

Control of hormone secretion rate – Control of hormone secretion rate – Role of negative feedbackRole of negative feedback

Endocrinecell Target cell

Hormone

Too much function

-

+

Hormone receptors?Hormone receptors?

Each target cell has 2000 – 100,000 receptors.

Mostly protein in structure.

Bind hormone with high affinity.

Hormone’s concentration in target tissues can be higher than in circulation.

Each receptor is highly specific for a single hormone.

Initiate a cascade of reactions in cell, where each stage of reaction becomes more powerful & active.

Minute quantities stimulus powerful & large final effect

Hormone receptors are dynamic in nature & their number respond to physiological & biochemical factors.

Receptor production is either down or up-regulated:

Down-regulated, when excess hormone:

( no of active receptors, either because of their inactivation

or destruction during the course of their fx.)

Up-regulated, when low or absent hormone:

( no of active receptors, as the stimulating hormone induces their new formation.)

Activation of Hormone receptorsActivation of Hormone receptors

Location of Hormone receptorsLocation of Hormone receptors

1. In or on surface of cell membrane: specific for protein, peptide, & catecholamine hormones.

2. In cell cytoplasm: for steroid hormones.

3. In cell nucleus: for thyroid hormones.

Mechanism of action of hormone?Mechanism of action of hormone?Activation of hormonal receptors play a

major role in hormonal action

3 ways:

1) Change in Membrane Permeability

2) Activation of an Intracellular Enzyme3) Activation of Genes

1) Change in membrane permeability1) Change in membrane permeability

Local hormone

Extra-cellular Cell membrane Intra-cellular

Opening or closing of one or more ions

channels, e.g. Na+; K+; Ca2+

Example:- Local hormone (neurotransmitter substances)- Adrenal medullary secretions (catecholamines) for Na+ & K+

…result in changing membrane potentials of specific smooth muscle cells

2) Activation of an intracellular enzyme2) Activation of an intracellular enzyme Hormonal-membrane receptor binding will

activate an enzyme immediately inside cell membrane, which will act as a second messenger.

Second messenger means that hormone itself is NOT the direct institute of the intracellular changes; instead, the ‘second messenger’ causes these effects.

Second messengers are very important:

1. Amplify the signal from receptor. 2. Relay station for chemical reaction to the signal

from the receptor.

Second messenger systemSecond messenger system There are 3 major classes of 2nd

messengers:

1) Cyclic Nucleutides: a. cAMP (cyclic adenosine monophosphate) - more important, & wide spread. b. cGMP (Cyclic guanosine monophosphate) - limited.

2) Inositol Triphosphate (IP3) & Diacylglycerol (DAG):

3) Ca2+: - muscle contraction - action potential - release of vesicles of neurotransmitter (Ach) - bone growth - regulation of Ca2+ concentration in ECF.

cAMP as a 2cAMP as a 2ndnd messenger intracellular system: messenger intracellular system:

Physiological intracellular responses & controlling cellular activity:

1. Activates enzymes such as protein kinase

2. Alters cell permeability3. Causes muscle contraction or

relaxation4. Causes protein synthesis

Many hormones exert their control of cell fx by cAMP mechanism,

1. Adrenocorticotropin (ACTH)2. Thyroid-stimulation hormone (TSH)3. Luteinizing hormone (LH)4. Follicle-stimulating hormone (FSH)5. Vasopressin (ADH)6. Parathyroid hormone (PTH)7. Glucagon8. Catecholamines9. Secretin10. Most hypothalamic releasing hormones

CaCa2+2+ & ‘Calmodulin’ as a 2 & ‘Calmodulin’ as a 2ndnd messenger system: messenger system:

hormon

e

Extra-Extra-cellularcellular

Cell Cell membramembranene

Intra-Intra-cellularcellular

CaCa2+2+ gategate

Biological actionsBiological actions (by activating a protein kinase(by activating a protein kinase whenwhen adding phosphate to proteinsadding phosphate to proteins ):): - causing smooth muscle contraction - causing smooth muscle contraction / / myosin kinasemyosin kinase - change secretion by secreting cells- change secretion by secreting cells - changes ciliary action- changes ciliary action

Ca2+

CaCa2+2+

CalmoduliCalmodulin proteinn protein

Membrane Phospholipid breakdown products as 2Membrane Phospholipid breakdown products as 2ndnd messengers – The ‘phosphatidylinositol’ system:messengers – The ‘phosphatidylinositol’ system:

Diacylglycerol

(DAG)

• Has biological effects

inside the cell. It acts as cAMP & IP3.

• Controls intracellular Ca2+ concentration

• Mobilizes Ca2+ from both

mitochondria & ER

3) Activation of Genes3) Activation of Genes Receptors are located

intracellularly.

Steroid hormones (fat soluble) receptors located in the cytoplasm.

Thyroid hormones (T4 & T3) receptors located in nucleus itself.

Activation of Genes – Steroid hormoneActivation of Genes – Steroid hormone

1. Entry

2. Combine w receptor

protein

3. Translocation to nucleus

4. Gene level - binds to chromatin - Influence DNA dependent RNA polymerase

Activation of Genes –Activation of Genes – Thyroid hormoneThyroid hormone

3. Translocation to nucleus

1. Entry

2. Combine w protein

5. Gene level - binds to chromatin - Influence DNA dependent RNA polymerase

4. Combine w receptor

protein

EndocrinopathiesEndocrinopathies Most endocrine disorders can be attributed

to one of the following problems:

1) Too little hormone, hyposecretion.

2) Too much hormone, hypersecretion; or

3) Abnormal tissue response to a hormone, end organ insensitivity or resistance.