Endocrine System Overview Hypothalamus and pituitary gland Hormones, receptors and their actions –Second messengers.

Endocrine System Endocrine System

Overview Overview Hypothalamus Hypothalamus

and pituitary and pituitary glandgland

Hormones, Hormones, receptors and receptors and their actionstheir actions– Second Second

messengersmessengers

Cell-Cell CommunicationCell-Cell Communication Necessary for integration Necessary for integration

of body activitiesof body activities MechanismsMechanisms

– neurotransmittersneurotransmitters released from neurons to released from neurons to

travel across gap to 2travel across gap to 2ndnd cell cell– gap junctionsgap junctions

holes in cell membranes holes in cell membranes between cells: links cells between cells: links cells electrically and electrically and metabolicallymetabolically

– paracrine (local) hormonesparacrine (local) hormones secreted into tissue fluids secreted into tissue fluids

to affect nearby cellsto affect nearby cells

Endocrine glandsEndocrine glands– produce produce hormoneshormones

HormoneHormone– chemical messenger chemical messenger

secreted into secreted into bloodstreambloodstream, , stimulates response in stimulates response in another tissue or organanother tissue or organ

Target cellsTarget cells– have have receptorsreceptors

for hormonefor hormone

Components of Endocrine SystemComponents of Endocrine System

Endocrine tissue

Endocrine cell

Interstitial space

Hormone Blood

Target tissue

DifferencesDifferences in Nervous and Endocrine in Nervous and Endocrine SystemsSystems

MeansMeans of communication of communication– nervous system has both nervous system has both

electrical and chemical electrical and chemical methodsmethods

– endocrine system has only endocrine system has only chemical methodschemical methods

SpeedSpeed and and persistencepersistence of of responseresponse– nervous system reacts quickly nervous system reacts quickly

(1 - 10 msec) and stops (1 - 10 msec) and stops quicklyquickly

– endocrine system reacts endocrine system reacts slowly (hormone release in slowly (hormone release in seconds or days), effect may seconds or days), effect may continue for weekscontinue for weeks

AreaArea of effect of effect– nervous system effects are nervous system effects are

targeted and specific (one targeted and specific (one organ or tissue)organ or tissue)

– endocrine system may have endocrine system may have general, widespread effects on general, widespread effects on many organsmany organs

SimilaritiesSimilarities in Nervous and Endocrine in Nervous and Endocrine SystemsSystems

Several chemicals function as both hormones and Several chemicals function as both hormones and neurotransmittersneurotransmitters– norepinephrine, epinephrine, dopaminenorepinephrine, epinephrine, dopamine

Some hormones secreted by “neuroendocrine” Some hormones secreted by “neuroendocrine” cells (neurons)cells (neurons)– oxytocin and antidiuretic hormoneoxytocin and antidiuretic hormone

Overlapping effects on same target cellsOverlapping effects on same target cells– norepinephrine and glucagon cause glycogen hydrolysis norepinephrine and glucagon cause glycogen hydrolysis

in liverin liver Systems regulate each otherSystems regulate each other

– neurons trigger hormone secretionneurons trigger hormone secretion– hormones stimulate or inhibit neuronshormones stimulate or inhibit neurons

Endocrine OrgansEndocrine Organs

Hypothalamohypophyseal AxisHypothalamohypophyseal AxisHypothalamusHypothalamus

Regulates primitive Regulates primitive functions from water functions from water balance to sex drivebalance to sex drive

Many functions carried Many functions carried out by pituitary glandout by pituitary gland

Pituitary Gland Pituitary Gland (Hypophysis)(Hypophysis)

Suspended from Suspended from hypothalamus by stalk hypothalamus by stalk (infundibulum)(infundibulum)

PosteriorPosterior and and anterioranterior partsparts

Hypothalamohypophyseal tract

Hypothalamohypophyseal portal system

Gonadotropin- releasing hormone controls FSH + LH releaseThyrotropin- releasing hormoneCorticotropin- releasing hormoneProlactin- releasing hormoneProlactin- inhibiting hormoneGH- releasing hormoneSomatostatin

Hypothalamohypophyseal Portal SystemHypothalamohypophyseal Portal System

Hormones (red box) secreted by anterior pituitary (under control of hypothalamic Hormones (red box) secreted by anterior pituitary (under control of hypothalamic releasers and inhibitors)releasers and inhibitors)

Hormones secreted by hypothalamus, travel in portal system to anterior pituitaryHormones secreted by hypothalamus, travel in portal system to anterior pituitary

Tropic hormones target other Tropic hormones target other endocrine glandsendocrine glands– gonadotropins target gonads, gonadotropins target gonads,

FSHFSH (follicle stimulating (follicle stimulating hormone) and hormone) and LHLH (luteinizing (luteinizing hormone)hormone)

– TSHTSH (thyroid stimulating (thyroid stimulating hormone)hormone)

– ACTHACTH (adrenocorticotropic (adrenocorticotropic hormone)hormone)

PRLPRL (prolactin) (prolactin) GHGH (growth hormone ) (growth hormone )

Pituitary Hormones - Pituitary Hormones - AnteriorAnterior Lobe Lobe

Pituitary Hormone ActionsPituitary Hormone ActionsAnterior Lobe HormonesAnterior Lobe Hormones

FSH FSH – ovaries, stimulates development of eggs and folliclesovaries, stimulates development of eggs and follicles– testes, stimulates production of spermtestes, stimulates production of sperm

LHLH– females, stimulates ovulation and corpus luteum to secrete progesterone females, stimulates ovulation and corpus luteum to secrete progesterone

and estrogenand estrogen– males, stimulates interstitial cells of testes to secrete testosteronemales, stimulates interstitial cells of testes to secrete testosterone

TSH TSH – stimulates growth of gland and secretion of thyroid hormone (TH)stimulates growth of gland and secretion of thyroid hormone (TH)

ACTH or corticotropinACTH or corticotropin– regulates response to stress, stimulates adrenal cortex to secrete of regulates response to stress, stimulates adrenal cortex to secrete of

corticosteroids that regulate glucose, fat & protein metabolismcorticosteroids that regulate glucose, fat & protein metabolism PRLPRL

– female, milk synthesis after deliveryfemale, milk synthesis after delivery– male, male, LH sensitivity, thus LH sensitivity, thus testosterone secretion testosterone secretion

GH or somatotropinGH or somatotropin– promotes tissue growthpromotes tissue growth

Stores and releases Stores and releases oxytocinoxytocin and and ADHADH

ADHADH– targets kidneys to targets kidneys to

water retention, water retention, reduce urinereduce urine

OxytocinOxytocin– labor contractions, labor contractions,

lactationlactation– possible role sperm possible role sperm

transport, emotional transport, emotional bondingbonding

Pituitary Hormones - Pituitary Hormones - PosteriorPosterior Lobe Lobe

Hormone ChemistryHormone Chemistry SteroidsSteroids

– derived from cholesterolderived from cholesterol– lipid soluble; water insoluble; hydrophobiclipid soluble; water insoluble; hydrophobic– act via intracellular receptorsact via intracellular receptors– turn on gene transcriptionturn on gene transcription

sex steroids, corticosteroidssex steroids, corticosteroids

Hormone ChemistryHormone Chemistry

Polypeptides and proteinsPolypeptides and proteins– small proteins made by small proteins made by

ER/GNER/GN– often processed and often processed and

modifiedmodified– water soluble; hydrophilicwater soluble; hydrophilic– act via membrane-bound act via membrane-bound

receptorsreceptors– modify existing metabolic modify existing metabolic

proteinsproteins Oxy, ADH; all releasing and Oxy, ADH; all releasing and

inhibiting hormones of inhibiting hormones of hypothalamus; most of hypothalamus; most of anterior pituitary hormonesanterior pituitary hormones

SteroidsSteroids

Hormone ChemistryHormone Chemistry

Monoamines (biogenic Monoamines (biogenic amines)amines)– derived from amino acids derived from amino acids

(usually tyrosine)(usually tyrosine)– water soluble; hydrophilicwater soluble; hydrophilic– act via membrane-bound act via membrane-bound

receptorsreceptors– modify existing metabolic modify existing metabolic

proteinsproteins catecholamines catecholamines

(norepinephrine, (norepinephrine, epinephrine, dopamine) epinephrine, dopamine) and thyroid hormonesand thyroid hormones

Polypeptides and proteinsPolypeptides and proteins

SteroidsSteroids

Hormone TransportHormone Transport

Monoamines and peptides/proteins are hydrophilic so Monoamines and peptides/proteins are hydrophilic so

mix easily with blood plasma – mix easily with blood plasma – dissolveddissolved

Steroids and thyroid hormone are hydrophobic and Steroids and thyroid hormone are hydrophobic and

must bind to must bind to transport proteinstransport proteins for transport for transport– bound hormonebound hormone - hormone attached to transport protein, - hormone attached to transport protein,

(prolongs half-life to weeks, protects from enzymes and (prolongs half-life to weeks, protects from enzymes and

kidney filtration)kidney filtration)

– only only unbound hormoneunbound hormone can leave capillary to reach target can leave capillary to reach target

cell (half-life a few minutes)cell (half-life a few minutes)

Transport proteins in blood plasmaTransport proteins in blood plasma

Hormone ReceptorsHormone Receptors Located on plasma Located on plasma

membrane (membrane-membrane (membrane-bound) or intracellular bound) or intracellular (soluble within cytoplasm (soluble within cytoplasm or nucleus)or nucleus)– sometimes found on the sometimes found on the

membrane of mitochondria membrane of mitochondria and other organelles, and other organelles,

– usually thousands for given usually thousands for given hormonehormone

– turn activities on or off turn activities on or off when hormone binds when hormone binds

metabolic pathways metabolic pathways gene expressiongene expression

Exhibit Exhibit specificityspecificity and and saturationsaturation

Hormone Mode of ActionHormone Mode of Action

Hydrophobic hormones Hydrophobic hormones (steroids and thyroid (steroids and thyroid hormone) penetrate by hormone) penetrate by diffusion of the plasma diffusion of the plasma membranemembrane– ultimately enter ultimately enter

nucleusnucleus Hydrophilic hormones Hydrophilic hormones

(monoamines and (monoamines and peptides) can not pass peptides) can not pass through membrane so through membrane so bind to membrane-bind to membrane-bound receptorsbound receptors– 22ndnd messenger messenger

activationactivation

Which is it?Which is it?

Receptor Response to LigandReceptor Response to Ligand

Change shape, change functionChange shape, change functionactivate internal proteins, enzymes, transcription factors etcactivate internal proteins, enzymes, transcription factors etc

Membrane Receptor ActionMembrane Receptor ActionIon Channel ActivationIon Channel Activation

Hormone binding to receptor results in Hormone binding to receptor results in depolarization or hyperpolarization of the membranedepolarization or hyperpolarization of the membrane

Membrane Receptor ActionMembrane Receptor ActionG-protein ActivationG-protein Activation

Hormone binding to receptor results in modification Hormone binding to receptor results in modification (activation or inhibition) of “downstream” enzymes (activation or inhibition) of “downstream” enzymes and 2and 2ndnd messenger formation or degradation messenger formation or degradation

E

L

R

GDP GTP

GDP

E*

L

R*

GTP

E*

L

R*

GTP GDP

E

L

R*

GDP

Second MessengersSecond Messengers

Cyclic nucleotides Cyclic nucleotides ((cAMPcAMP, cGMP), cGMP)

Diacylglycerol Diacylglycerol (DAG)(DAG)

Inositol Inositol triphosphate (IP3)triphosphate (IP3)

CalciumCalcium

cAMP as a Second MessengercAMP as a Second Messenger

1) Hormone binding 1) Hormone binding activates G proteinactivates G protein

2) GP activates adenylate 2) GP activates adenylate cyclasecyclase

3) AC produces cAMP3) AC produces cAMP4) cAMP activates kinases4) cAMP activates kinases5) Kinases activate 5) Kinases activate

enzymesenzymes6) Metabolic reactions: 6) Metabolic reactions:

synthesis, secretion, synthesis, secretion, degradation, altered degradation, altered membrane potentialsmembrane potentials

Membrane Receptor ActionMembrane Receptor ActionEnzyme Receptor ActivationEnzyme Receptor Activation

Hormone binding to receptor results in activation of intrinsic Hormone binding to receptor results in activation of intrinsic (receptor) enzyme and “downstream” metabolic changes(receptor) enzyme and “downstream” metabolic changes

Membrane Receptor ActionMembrane Receptor ActionIntracellular ReceptorsIntracellular Receptors

Hormone binding to receptor results in activation of Hormone binding to receptor results in activation of transcription factors and gene expressiontranscription factors and gene expression

Hormone Hormone

Membrane -bound Intracellular

receptor receptor

Receptor linked Receptor linked Receptor linked Activates

to ion channel to G protein to enzyme genes

Opens or closes Activates already Synthesizes

Ion channels existing enzymes enzymes

Cell Response

Summary of Hormonal ActionsSummary of Hormonal Actions

Regulation of Hormone SecretionRegulation of Hormone Secretion Non-hormonalNon-hormonal

– Control of release Control of release dependent upon dependent upon concentration of other concentration of other non-hormonal non-hormonal substance substance (i.e., glucose)(i.e., glucose)

Regulation of Hormone SecretionRegulation of Hormone Secretion

Non-hormonalNon-hormonal NeuronalNeuronal

– Secretion or Secretion or inhibition of release inhibition of release influenced by influenced by emotions or stressemotions or stress

Regulation of Hormone SecretionRegulation of Hormone Secretion

Non-hormonalNon-hormonal NeuronalNeuronal HormonalHormonal

– Control of release Control of release regulated by regulated by other hormones other hormones

Review questionsReview questions1.1. What are the different methods of cell to cell signaling? Provide an What are the different methods of cell to cell signaling? Provide an

example of where/when each method occurs.example of where/when each method occurs.2.2. Name and approximately locate the main endocrine glands.Name and approximately locate the main endocrine glands.3.3. Compare and contrast the nervous and endocrine systems.Compare and contrast the nervous and endocrine systems.4.4. Describe the relationship between the hypothalamus and the pituitary Describe the relationship between the hypothalamus and the pituitary

gland. What is the tract system? What about the portal system?gland. What is the tract system? What about the portal system?5.5. Which hormones are released from the anterior pituitary and which from Which hormones are released from the anterior pituitary and which from

the posterior pituitary? Briefly describe the actions of these hormones on the posterior pituitary? Briefly describe the actions of these hormones on their targets.their targets.

6.6. What are releasing and inhibiting hormones? Where are they released What are releasing and inhibiting hormones? Where are they released from? What is there target (usually)?from? What is there target (usually)?

7.7. Compare and contrast the main classes/types of hormones Compare and contrast the main classes/types of hormones andand their their receptors.receptors.

8.8. What different ways do membrane-bound receptors act upon their target What different ways do membrane-bound receptors act upon their target cell? Provide an example of each of these types of activity.cell? Provide an example of each of these types of activity.

9.9. Explain how intracellular receptors differ from membrane-bound receptors Explain how intracellular receptors differ from membrane-bound receptors (include cellular location and mechanism of action).(include cellular location and mechanism of action).

10.10. Briefly summarize the cellular effect of hydrophilic hormone activation and Briefly summarize the cellular effect of hydrophilic hormone activation and hydrophobic hormone activation. hydrophobic hormone activation.

11.11. What are second messengers and why are they important? Be able to What are second messengers and why are they important? Be able to provide at least one example of cAMP acting as a second messenger.provide at least one example of cAMP acting as a second messenger.

12.12. How is hormonal release regulated? Provide an example for each way.How is hormonal release regulated? Provide an example for each way.