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ENDOCRINE SYSTEM ENDOCRINE SYSTEM

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Page 1: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

ENDOCRINE ENDOCRINE SYSTEMSYSTEM

Page 2: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

ENDOCRINE SYSTEMENDOCRINE SYSTEM• Endocrine system

– Composed of glands• “Ductless glands”

– Secrete chemical signals into the bloodstream• (Exocrine glands secrete

substances through ducts to surfaces)

– Secretory products are hormones

Page 3: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

HORMONESHORMONES• Hormones

– Chemical signal (“ligand”)

– Produced in minute amounts by a collection of cells

– Secreted into the interstitial spaces

– Enters the circulatory system

– Transported throughout the body

– Influences the activity of specific tissues• “Target tissues”

Page 4: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

REGULATIONREGULATION• Endocrine and nervous systems both regulate the

activities of structures within the body– Accomplished in different ways

– Hormones are amplitude-modulated signals• Signals consist mainly of increases or decreases in the

concentration of hormones in body fluids• Response produced within several seconds to hours

– Action potentials are frequency-modulated signals• Action potentials vary in frequency but not in amplitude• Response produced within milliseconds

Page 5: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

REGULATIONREGULATION• Nervous and endocrine systems are intimately related

– The two systems cannot be completely separated either anatomically or functionally

– e.g., Some neurons secrete neurohormones into the circulatory system• Function like hormones

– e.g., Some neurons directly innervate endocrine glands and influence their secretory activity

– e.g., Some hormones secreted by endocrine glands affect the nervous system and influence its activity

Page 6: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CHEMICAL SIGNALSCHEMICAL SIGNALS• Intercellular chemical signals allow cells to

communicate with each other– e.g., Neurotransmitters, neuromodulators, and hormones

• There are various types of intercellular signals– Autocrine chemical signals

– Paracrine chemical signals

– Pheromones

Page 7: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CHEMICAL SIGNALSCHEMICAL SIGNALS• Autocrine chemical signals

– Released by cells and have an effect on similar cells

– e.g., Prostaglandins are released by smooth muscle cells and platelets in response to inflammation• Causes aggregation of platelets and relaxation of blood

vessel smooth muscle

Page 8: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CHEMICAL SIGNALSCHEMICAL SIGNALS• Paracrine chemical signals

– Released by cells and affect other cell types locally without being transported in the blood

– e.g., The peptide somatostatin is released by cells in the pancreas and functions locally to inhibit the secretion of insulin from other cells of the pancreas

Page 9: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CHEMICAL SIGNALSCHEMICAL SIGNALS• Pheromones

– Secreted into the environment and modify the behavior and physiology of other individuals

– e.g., Pheromones released in urine of cats and dogs signal fertility

– e.g., Pheromones released by women influence the menstrual cycles of other women

Page 10: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CHEMICAL SIGNALSCHEMICAL SIGNALS• Many intercellular chemical signals consistently

• Intercellular signals– Many consistently fit one specific definition

– Many do not consistently fit one specific definition

– e.g., Norepinephrine functions both as a neurotransmitter and a neurohormone

Page 11: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances
Page 12: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances
Page 13: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

HORMONE STRUCTUREHORMONE STRUCTURE• Three main classes of hormones

– Polymers of amino acids• Proteins or polypeptides• Glycoprotein hormones contain carbohydrate components

– Derivatives of single amino acids

– Lipids• Steroids or derivatives of fatty acids

Page 14: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances
Page 15: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances
Page 16: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

SECRETIONSECRETION• Most hormones are not secreted at a constant rate

– Secretion increases and decreases dramatically over time

– Secretion rate generally controlled by negative feedback• Body activity regulated is maintained within normal range• Homeostasis is maintained

– Secretion is sometimes regulated by positive feedback• Less frequent• e.g., components of the female reproductive system

– Estrogen stimulates LH secretion

– LH stimulates estrogen secretion

Page 17: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

SECRETIONSECRETION• Three major patterns of regulation

– Changes in the extracellular concentration of a non-hormone molecule can affect an endocrine gland

– Neural control of the endocrine gland

– Control of hormone secretion by another hormone or neurohormone

• Regulation of hormone secretion often involves more than one of these mechanisms

Page 18: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

SECRETIONSECRETION• Changes in the extracellular concentration of a non-

hormone molecule can affect an endocrine gland– e.g., Blood glucose

levels affect insulin secretion from the pancreas

– Insulin increases glucose movement into cells

– Insulin secretion decreases

Page 19: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

SECRETIONSECRETION• Neural control of the endocrine gland

– Neurons synapse with hormone-producing cells

– Neurotransmitter release stimulates or inhibits hormone release

– e.g., Stress or exercise stimulates the adrenal gland to secrete epinephrine and norepinephrine

Page 20: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

SECRETIONSECRETION• Control of hormone secretion by another hormone or

neurohormone– e.g., Thyroid-releasing hormone (TRH) from the

hypothalamus stimulates the secretion of thyroid-stimulating hormone (TSH) from the anterior pituitary gland

– TSH stimulates the secretion of thyroid hormones (T3 & T4)

– etc.

Page 21: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

SECRETIONSECRETION• Some hormones are in the circulatory system at

relatively constant levels– e.g., Thyroid hormones

• Levels of some hormones change suddenly in response to certain stimuli– e.g., Epinephrine is released in response to stress or

exercise• Levels of some hormones change in relatively constant

cycles– e.g., Reproductive hormones cycle in women during

their reproductive years

Page 22: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

SECRETIONSECRETION• Some hormones are in the circulatory system at

relatively constant levels– e.g., Thyroid hormones

Page 23: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

SECRETIONSECRETION• Levels of some hormones change suddenly in response

to certain stimuli– e.g., Epinephrine is released in response to stress or

exercise

Page 24: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

SECRETIONSECRETION• Levels of some hormones change in relatively constant

cycles– e.g., Reproductive

hormones cycle in women during their reproductive years

Page 25: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

HORMONE TRANSPORTHORMONE TRANSPORT• Hormones are dissolved in blood plasma

• Transported in two fashions– Free form

– Bound to plasma proteins

Page 26: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

HORMONE TRANSPORTHORMONE TRANSPORT• Free hormones diffuse readily into interstitial spaces

– Concentration of hormone in the blood affects the amount of hormone diffusing into interstitial spaces

Page 27: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

HORMONE TRANSPORTHORMONE TRANSPORT• Many hormones bind only to certain types of plasma

proteins– e.g., The type of plasma protein binding to thyroid

hormones differs from the type of plasma protein binding to testosterone

Page 28: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

HORMONE TRANSPORTHORMONE TRANSPORT• Hormones that bind to plasma proteins do so reversibly

– H + BP HBP

– This equilibrium is important• Only free hormone can diffuse into the interstitial space• Hormones bound to plasma proteins tend to remain at a

relatively constant level in the blood for long periods of time

– Decrease in plasma protein concentration reduces half-life of hormone

Page 29: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

HORMONE TRANSPORTHORMONE TRANSPORT• A decrease in plasma protein concentration reduces the

half-life of hormone– Eliminated in either the kidneys of the liver

Page 30: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

HORMONE TRANSPORTHORMONE TRANSPORT• The circulatory system quickly distributes hormones throughout

the body– Diffuse through capillary endothelium

• Rate varies between hormones

– Lipid-soluble hormones readily diffuse through the walls of all capillaries

– Water-soluble hormones pass through pores (“fenestrae”) in the capillary endothelium

• Capillary endothelia of organs regulated by protein hormones have large pores

• Endocrine glands secreting these hormones also have large pores

Page 31: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

METABOLISM & EXCRETIONMETABOLISM & EXCRETION• Hormone destruction and elimination limit the time in

which they are active– Water-soluble hormones have relatively short half-lives

• Rapidly degraded by enzymes– Present in circulatory system or organs

• Normally have concentrations that increase and decrease rapidly

• Generally regulate activities that have a rapid onset and a short duration

Page 32: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

METABOLISM & EXCRETIONMETABOLISM & EXCRETION• Hormone destruction and elimination limit the time in

which they are active– Lipid-soluble hormones have relatively long half-lives

• Commonly circulate in the blood bound to plasma proteins

– Reduces rate of elimination

– Reduces rate at which they diffuse through capillary endothelium

• Normally maintained at relatively constant levels

Page 33: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

METABOLISM & EXCRETIONMETABOLISM & EXCRETION• Four main modes of hormone removal from the blood

– Excretion

– Metabolism

– Active transport

– Conjugation

Page 34: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

METABOLISM & EXCRETIONMETABOLISM & EXCRETION• Four main modes of hormone removal from the blood

– Excretion• Kidneys excrete hormones into the urine• Liver excretes hormones into the bile

Page 35: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

METABOLISM & EXCRETIONMETABOLISM & EXCRETION• Four main modes of hormone removal from the blood

– Metabolism• Hormones metabolized or chemically modified

– Enzymes in blood or tissues• e.g., Liver, kidneys, lungs, etc.

• End products may be excreted in urine or bile• End products may be taken up by cells• e.g., Epinephrine is modified, then excreted• e.g., Protein hormones are broken down into amino acids

– Amino acids are then taken up by cells

Page 36: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

METABOLISM & EXCRETIONMETABOLISM & EXCRETION• Four main modes of hormone removal from the blood

– Active transport• Actively transported into cells• Hormones are recycled• e.g., Epinephrine and norepinephrine are actively

transported into cells– These hormones can be secreted again

Page 37: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

METABOLISM & EXCRETIONMETABOLISM & EXCRETION• Four main modes of hormone removal from the blood

– Conjugation• Attachment of water-soluble molecules to hormones• Typically sulfate or glucuronic acid• Increases rate of excretion by kidneys or liver

Page 38: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances
Page 39: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

INTERACTION WITH TARGET TISSUESINTERACTION WITH TARGET TISSUES

• Intercellular chemical signals– “Ligands”

– Bind to proteins and change their functions

– Various classes• Hormones• Neurotransmitters• Chemical mediators of inflammation

Page 40: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

INTERACTION WITH TARGET TISSUESINTERACTION WITH TARGET TISSUES

• Ligands bind to proteins at their binding site– Receptor site if protein is a receptor

• Lock-and-key fit

• “Specificity”– e.g., Insulin binds to

insulin receptors

– e.g., Insulin does not bind to growth hormone receptors

• Multiple types of receptors exist for some hormones– e.g., There are multiple types of epinephrine receptors

Page 41: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

INTERACTION WITH TARGET TISSUESINTERACTION WITH TARGET TISSUES

• Hormones are distributed throughout the body by the circulatory system– Target cells respond

to a given hormone• Possess receptors

to which the hormone binds

• Cells lacking receptors do not respond

Page 42: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

INTERACTION WITH TARGET TISSUESINTERACTION WITH TARGET TISSUES

• Drugs with structures similar to a particular chemical signal may compete with that molecule for their receptor sites– Binding some drugs activates the receptors

– Binding of some drugs inhibits the receptor• Blocks binding by the hormone• e.g., RU486 binds to progesterone receptors

– Prevents binding by progesterone

– Prevents the maintenance of pregnancy

Page 43: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

INTERACTION WITH TARGET TISSUESINTERACTION WITH TARGET TISSUES

• Response to a given concentration of chemical signal– Constant in some cases– Variable in some cases

• Two common reasons• Fatigue in the target cells after prolonged stimulation• Number of receptors can decrease after exposure to

certain chemical signals– “Down-regulation”– Two mechanisms

• Decreased rate of receptor synthesis• Increased rate of receptor degradation

Page 44: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

INTERACTION WITH TARGET TISSUESINTERACTION WITH TARGET TISSUES

• Neurons of the hypothalamus release GnRH

• Causes secretion of FSH and LH from the anterior pituitary

• Exposure to GnRH causes a reduction in the number of GnRH receptors in cells of the anterior pituitary

• Dramatic decrease several hours after exposure

• Pituitary becomes less sensitive to GnRH

• Normal response of pituitary depends on periodic (not constant) exposure to GnRH

Page 45: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

INTERACTION WITH TARGET TISSUESINTERACTION WITH TARGET TISSUES

• Tissues exhibiting down-regulation of receptors generally respond to short-term increases in hormone concentrations– Tissues responding to relatively constant levels of

hormones normally do not exhibit down-regulation

Page 46: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

INTERACTION WITH TARGET TISSUESINTERACTION WITH TARGET TISSUES

• Periodic increases in sensitivity to certain hormones can also occur– “Up-regulation”

– Results from an increase in the rate of receptor molecule synthesis

– e.g., Increased number of LH receptors in the ovary during each menstrual cycle

– FSH from pituitary increases synthesis of LH receptor

Page 47: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances
Page 48: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Two main categories of chemical signals

• (And two main categories of receptors)– Those binding to membrane-bound receptors

– Those binding to intracellular receptors

Page 49: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Some chemical signals cannot pass through the plasma

membrane– Large molecules and

water-soluble molecules– Bind to membrane-bound

receptors• Transmembrane receptor

proteins• Receptor site exposed on outer surface• Binding of signal to receptor initiates a response inside the

cell

Page 50: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Some chemical signals readily pass through the plasma

membrane– Small and lipid soluble molecules

– Bind to intracellular receptors

– Hormone-receptor complex may bind to DNA• Alters gene expression

– Hormone-receptor complex may bind to enzymes

Page 51: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORSSignals binding to membrane-

bound receptors• Protein hormones• Glycoprotein hormones• Polypeptides• Some smaller molecules

– Epinephrine

– Norepinephrine

• etc.

Signals binding to intracellular receptors

• Thyroid hormones• Steroid hormones

– Testosterone

– Estrogen

– Progesterone

– Aldosterone

– Cortisol

– etc.

Page 52: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Membrane-bound receptors

– Integral membrane proteins

– Hormone-receptor binding is reversible

– Binding stimulates the intracellular portion of receptor to initiate a response• Three major mechanisms of responses

– Altered membrane permeability

– Altered activity of G proteins

– Altered activity of intracellular enzymes

Page 53: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Receptors altering membrane permeability

– Some receptors comprise part of an ion channel• Ligand-gated ion channels

– Binding alters shape of channel• Causes channel to either

open or close

– Results in a change in the membrane’s permeability to the specific ions passing through the channel

Page 54: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances
Page 55: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Receptors activating G proteins

• G proteins– Bind to receptors

at inner surface of plasma membrane

– Inactive state binds to GDP

Page 56: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Receptors activating G proteins

– Receptor changes shape upon binding to hormone• GTP replaces GDP on G protein

• Alpha subunit separates from other subunits

• Alpha subunit can influence ion channels or form intracellular mediators (“second messengers”)

Page 57: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Receptors activating G proteins

– Hormone separates from the receptor

– G proteins are no longer activated

– Alpha subunits are inactivated as GTP GDP

Page 58: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Receptors activating G proteins

– Some G proteins activate Ca2+ channels

– Ca2+ enters the cell

– Can function as an intracellular mediator• Enters or is synthesized inside the cell• Regulates enzyme activities inside the cell

Page 59: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Receptors activating G proteins

– Ca2+ can combine with calmodulin molecules

– Calcium-calmodulin complexes activate enzymes

– Thee enzymes cause contraction of smooth muscle

Page 60: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Receptors activating G proteins

– Some G proteins alter enzyme activity • Activated alpha subunits can activate the enzyme adenylate cyclase• ATP cAMP

– cAMP binds to kinases• Activated kinases phosphorylate

other enzymes• Activity of these enzymes is

altered– Either increased or decreased

• cAMP is inactivated (cAMP AMP) by the enzyme phosphodiesterase

Page 61: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Cyclic AMP acts as an intracellular mediator in many

cell types– Enzymes activated are different

– Response of each cell type is different

– e.g., Glucagon release of glucose from liver cells

– e.g., LH ovulation

Page 62: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• The combination of chemical signals with their

receptors doesn’t always result in increased cAMP synthesis– Sometimes cAMP synthesis is inhibited by G proteins

– There are other common intracellular mediators• e.g., Diacyl glycerol (DAG)

• e.g., Inositol triphosphate (IP3)

Page 63: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Epinephrine binds to certain receptors in some types of smooth

muscle– Binding activates a G protein– Phospholipase C is activated

• Phosphoinositol diphosphate (PIP2) DAG + IP3

– DAG activates enzymes that synthesize prostaglandins

• Smooth muscle contraction is increased

– IP3 releases Ca2+ from the E.R.• Ca2+ enters the cytoplasm and

increases smooth muscle contraction

Page 64: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Some receptors directly alter the activity of intracellular

enzymes– Intracellular enzymes controlled by the membrane-bound

receptors• May be part of the receptor• May be separate molecules

Page 65: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Some receptors directly alter the activity of intracellular

enzymes– Effects of altered enzyme activity

• Increased or decreased synthesis of intracellular mediator molecules

• Phosphorylation of intracellular proteins

– Effects of intracellular mediators or phosphorylated proteins• Activation of processes that produce the response of cells

to the chemical signals

Page 66: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Some receptors directly alter the activity of intracellular

enzymes– Intracellular mediator molecules act as chemical signals

• Move from enzymes that produced them into the cytoplasm

• Activate processes that produce the response of the cell

Page 67: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Some receptors directly alter the activity of intracellular

enzymes– Cyclic guanine monophosphate

• cGMP

• Intracellular mediator molecule

• Synthesized in response to chemical signal binding with a membrane-bound receptor

• Produced by the enzyme guanylate cyclase

– GTP cGMP

Page 68: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Some receptors directly alter the activity of intracellular

enzymes– Cyclic guanine monophosphate

• Combine with and activate specific cytoplasmic enzymes

• Activated enzymes produce the response of the cell to the chemical signal

Page 69: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Some receptors directly alter the activity of intracellular

enzymes– e.g., ANH binds to receptor in

kidney cell membrane– Increased cGMP synthesis

• Influences action of enzymes• Stimulates Na+ and H2O

excretion– Phosphodiesterase breaks

down cGMP• cGMP GMP

– Signal quickly disappears when hormone disappears

Page 70: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Some receptors directly alter the activity of intracellular

enzymes– Cytoplasmic portion of receptor acts as a phosphorylase enzyme

– Phosphorylates several specific proteins• Some are part of the

membrane-bound receptor

• Others are cytoplasmic

• proteins

– Phosphorylated proteins influence activity of other cytoplasmic enzymes

Page 71: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Many hormones stimulate the synthesis of an

intracellular mediator molecule– Often produce rapid responses

– Mediator influences already-existing enzymes

– Causes a cascade event• Few mediator molecules activate several enzymes• Each activated enzyme activates several other enzymes• Final response is produced

Page 72: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances
Page 73: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Intracellular receptors

– Present in either the cell’s cytoplasm or nucleus

• Lipid-soluble chemical signals– Cross the plasma membrane

– Bind to intracellular receptors

• Hormone-receptor complex has one of two effects– Alter the activity of cellular enzymes

– Bind to DNA and alter the expression of genes

Page 74: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Receptors binding to DNA

– Activate certain specific genes• Transcription of these genes

increases

• Specific proteins are produced

– e.g., Testosterone and estrogen stimulate the production of the proteins responsible for secondary sexual characteristics

– e.g., Aldosterone stimulates kidney cells to synthesize proteins increasing the rate of Na+ and K+ transport

• Results in increased reabsorption of Na+ and increased K+ secretion

Page 75: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS

Page 76: ENDOCRINE SYSTEM. Endocrine system –Composed of glands “Ductless glands” –Secrete chemical signals into the bloodstream (Exocrine glands secrete substances

CLASSES OF RECEPTORSCLASSES OF RECEPTORS• Cells synthesizing proteins in response to hormonal

stimuli normally have a latent period of several hours– Hormones bind, responses are observed