16 The Endocrine System:. Endocrine System: Overview Acts with the nervous system to coordinate and integrate the activity of body cells Acts with the

1616The Endocrine System: The Endocrine System:

Endocrine System: Endocrine System: OverviewOverview

Acts with the nervous system to coordinate Acts with the nervous system to coordinate and integrate the activity of body cellsand integrate the activity of body cells

Influences metabolic activities by means of Influences metabolic activities by means of hormones transported in the blood hormones transported in the blood

Responses occur more slowly but tend to last Responses occur more slowly but tend to last longer than those of the nervous systemlonger than those of the nervous system

Endocrine glands: pituitary, thyroid, Endocrine glands: pituitary, thyroid, parathyroid, adrenal, and pineal glands parathyroid, adrenal, and pineal glands

Endocrine System: Endocrine System: OverviewOverview

Some organs produce both hormones and Some organs produce both hormones and exocrine products (e.g., pancreas and exocrine products (e.g., pancreas and gonads)gonads)

The hypothalamus has both neural and The hypothalamus has both neural and endocrine functions endocrine functions

Other tissues and organs that produce Other tissues and organs that produce hormones include adipose cells, thymus, cells hormones include adipose cells, thymus, cells in the walls of the small intestine, stomach, in the walls of the small intestine, stomach, kidneys, and heartkidneys, and heart

Copyright © 2010 Pearson Education, Inc. Figure 16.1

Pineal glandHypothalamus

Pituitary gland

Parathyroid glands(on dorsal aspectof thyroid gland)Thymus

Thyroid gland

Adrenal glands

Pancreas

Ovary (female)

Testis (male)

Chemical MessengersChemical Messengers

Hormones: long-distance chemical signals Hormones: long-distance chemical signals that travel in the blood or lymphthat travel in the blood or lymph

Autocrines: chemicals that exert effects on Autocrines: chemicals that exert effects on the same cells that secrete themthe same cells that secrete them

Paracrines: locally acting chemicals that Paracrines: locally acting chemicals that affect cells other than those that secrete affect cells other than those that secrete themthem

Autocrines and paracrines are local chemical Autocrines and paracrines are local chemical messengers and will not be considered part of messengers and will not be considered part of the endocrine systemthe endocrine system

Chemistry of HormonesChemistry of Hormones

Two main classesTwo main classes1.1. Amino acid-based hormones Amino acid-based hormones

Amines, thyroxine, peptides, and proteinsAmines, thyroxine, peptides, and proteins

2.2. SteroidsSteroids Synthesized from cholesterolSynthesized from cholesterol Gonadal and adrenocortical hormonesGonadal and adrenocortical hormones

Mechanisms of Mechanisms of Hormone ActionHormone Action

Hormone action on target cellsHormone action on target cells1.1. Alter plasma membrane permeability of Alter plasma membrane permeability of

membrane potential by opening or closing ion membrane potential by opening or closing ion channelschannels

2.2. Stimulate synthesis of proteins or regulatory Stimulate synthesis of proteins or regulatory molecules molecules

3.3. Activate or deactivate enzyme systemsActivate or deactivate enzyme systems4.4. Induce secretory activityInduce secretory activity5.5. Stimulate mitosisStimulate mitosis


Two mechanisms, depending on their Two mechanisms, depending on their chemical naturechemical nature

1.1. Water-soluble hormones (all amino acid–Water-soluble hormones (all amino acid–based hormones except thyroid hormone)based hormones except thyroid hormone) Cannot enter the target cellsCannot enter the target cells Act on plasma membrane receptorsAct on plasma membrane receptors Coupled by G proteins (signal Coupled by G proteins (signal

transducer) to intracellular second transducer) to intracellular second messengers that mediate the target messengers that mediate the target cell’s responsecell’s response


2.2. Lipid-soluble hormones (steroid and Lipid-soluble hormones (steroid and thyroid hormones)thyroid hormones)

Act on intracellular receptors that Act on intracellular receptors that directly activate genesdirectly activate genes

Copyright © 2010 Pearson Education, Inc. Figure 16.2, step 1

Hormone (1st messenger)binds receptor.

Receptor

Hormones thatact via cAMPmechanisms:

EpinephrineACTHFSHLH

Extracellular fluid

Cytoplasm

GlucagonPTHTSHCalcitonin

1



Receptoractivates Gprotein (GS).

Receptor

G protein (GS)



Extracellular fluid

Cytoplasm

GDP


1

2




G proteinactivatesadenylatecyclase.

Receptor

G protein (GS)

Adenylate cyclase



Extracellular fluid

Cytoplasm

GDP


1

2 3





Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).

Receptor

G protein (GS)

Adenylate cyclase



Extracellular fluid

Cytoplasm

GDP


1

2 3 4





cAMP acti-vates proteinkinases.

Adenylatecyclaseconverts ATPto cAMP (2ndmessenger).

Receptor

G protein (GS)

Adenylate cyclase

Triggers responses oftarget cell (activatesenzymes, stimulatescellular secretion,opens ion channel,etc.)



Inactiveprotein kinase

Extracellular fluid

Cytoplasm

Activeproteinkinase

GDP


1

2 3 4

5

Intracellular Receptors Intracellular Receptors and Direct Gene and Direct Gene

ActivationActivation


Receptor-hormonecomplex

Receptorprotein

Cytoplasm

Nucleus

Extracellular fluid

Steroidhormone

The steroid hormonediffuses through the plasmamembrane and binds anintracellular receptor.

Plasmamembrane

1



Receptorprotein

Cytoplasm

Nucleus

Extracellular fluid

Steroidhormone


The receptor-hormone complex entersthe nucleus.

Plasmamembrane

1

2


DNA

Hormoneresponseelements


Receptorprotein

Cytoplasm

Nucleus

Extracellular fluid

Steroidhormone



The receptor- hormonecomplex binds a hormoneresponse element (aspecific DNA sequence).

Plasmamembrane

1

2

3


mRNA

DNA



Receptorprotein

Cytoplasm

Nucleus

Extracellular fluid

Steroidhormone




Binding initiatestranscription of thegene to mRNA.

Plasmamembrane

1

2

3

4


mRNA

New protein

DNA



Receptorprotein

Cytoplasm

Nucleus

Extracellular fluid

Steroidhormone




Binding initiatestranscription of thegene to mRNA.

The mRNA directsprotein synthesis.

Plasmamembrane

1

2

3

4

5

Target Cell SpecificityTarget Cell Specificity

Target cells must have specific receptors to Target cells must have specific receptors to which the hormone bindswhich the hormone binds ACTH receptors are only found on certain cells ACTH receptors are only found on certain cells

of the adrenal cortexof the adrenal cortex Thyroxin receptors are found on nearly all cells Thyroxin receptors are found on nearly all cells

of the bodyof the body

Target Cell ActivationTarget Cell Activation

Target cell activation depends on three factorsTarget cell activation depends on three factors1.1. Blood levels of the hormoneBlood levels of the hormone

2.2. Relative number of receptors on or in the target Relative number of receptors on or in the target cellcell

3.3. Affinity of binding between receptor and hormoneAffinity of binding between receptor and hormone

Hormones influence the number of their receptorsHormones influence the number of their receptors Up-regulation—target cells form more receptors in Up-regulation—target cells form more receptors in

response to the hormoneresponse to the hormone Down-regulation—target cells lose receptors in Down-regulation—target cells lose receptors in

response to the hormoneresponse to the hormone

Hormones in the BloodHormones in the Blood

Hormones circulate in the blood either free Hormones circulate in the blood either free or bound to a carrieror bound to a carrierSteroids and thyroid hormone are attached Steroids and thyroid hormone are attached

to plasma proteinsto plasma proteinsAll others circulate without carriersAll others circulate without carriers

The concentration of a circulating hormone The concentration of a circulating hormone reflects: reflects: Rate of releaseRate of releaseSpeed of inactivation and removal from the Speed of inactivation and removal from the

bodybody

Hormones in the BloodHormones in the Blood

Hormones are removed from the blood byHormones are removed from the blood by Degrading enzymesDegrading enzymes KidneysKidneys Liver Liver Half-life—the time required for a hormone’s Half-life—the time required for a hormone’s

blood level to decrease by halfblood level to decrease by half

Interaction of Hormones Interaction of Hormones at Target Cellsat Target Cells

Multiple hormones may interact in several Multiple hormones may interact in several waysways Permissiveness: one hormone cannot exert its Permissiveness: one hormone cannot exert its

effects without another hormone being presenteffects without another hormone being present Synergism: more than one hormone produces Synergism: more than one hormone produces

the same effects on a target cellthe same effects on a target cell Antagonism: one or more hormones opposes Antagonism: one or more hormones opposes

the action of another hormonethe action of another hormone

Control of Hormone Control of Hormone ReleaseRelease

Blood levels of hormonesBlood levels of hormones Are controlled by negative feedback systemsAre controlled by negative feedback systems Vary only within a narrow desirable rangeVary only within a narrow desirable range

Hormones are synthesized and released in Hormones are synthesized and released in response toresponse to1.1. Humoral stimuliHumoral stimuli2.2. Neural stimuliNeural stimuli3.3. Hormonal stimuliHormonal stimuli

Humoral StimuliHumoral Stimuli

Changing blood levels of ions and nutrients Changing blood levels of ions and nutrients directly stimulates secretion of hormones directly stimulates secretion of hormones

Example: CaExample: Ca2+2+ in the blood in the blood Declining blood CaDeclining blood Ca2+2+ concentration stimulates concentration stimulates

the parathyroid glands to secrete PTH the parathyroid glands to secrete PTH (parathyroid hormone)(parathyroid hormone)

PTH causes CaPTH causes Ca2+2+ concentrations to rise and the concentrations to rise and the stimulus is removedstimulus is removed

Copyright © 2010 Pearson Education, Inc. Figure 16.4a

(a) Humoral Stimulus

Capillary (lowCa2+ in blood)

Parathyroidglands

Thyroid gland(posterior view)

PTH

Parathyroidglands

1 Capillary blood containslow concentration of Ca2+,which stimulates…

2 …secretion ofparathyroid hormone (PTH)by parathyroid glands*

Neural StimuliNeural Stimuli

Nerve fibers stimulate hormone releaseNerve fibers stimulate hormone release Sympathetic nervous system fibers stimulate Sympathetic nervous system fibers stimulate

the adrenal medulla to secrete catecholamines the adrenal medulla to secrete catecholamines

Copyright © 2010 Pearson Education, Inc. Figure 16.4b

(b) Neural Stimulus

CNS (spinal cord)

Medulla ofadrenalgland

Preganglionicsympatheticfibers

Capillary

1 Preganglionic sympatheticfibers stimulate adrenalmedulla cells…

2 …to secrete catechola-mines (epinephrine andnorepinephrine)

Hormonal StimuliHormonal Stimuli

Hormones stimulate other endocrine organs Hormones stimulate other endocrine organs to release their hormones to release their hormones Hypothalamic hormones stimulate the release Hypothalamic hormones stimulate the release

of most anterior pituitary hormonesof most anterior pituitary hormones Anterior pituitary hormones stimulate targets to Anterior pituitary hormones stimulate targets to

secrete still more hormonessecrete still more hormones Hypothalamic-pituitary-target endocrine organ Hypothalamic-pituitary-target endocrine organ

feedback loop: hormones from the final target feedback loop: hormones from the final target organs inhibit the release of the anterior organs inhibit the release of the anterior pituitary hormonespituitary hormones

Copyright © 2010 Pearson Education, Inc. Figure 16.4c

(c) Hormonal Stimulus

Hypothalamus

Thyroidgland

Adrenalcortex

Gonad(Testis)

Pituitarygland

1 The hypothalamus secreteshormones that…

2 …stimulatethe anteriorpituitary glandto secretehormonesthat…

3 …stimulate other endocrineglands to secrete hormones

Nervous System Nervous System ModulationModulation

The nervous system modifies the stimulation The nervous system modifies the stimulation of endocrine glands and their negative of endocrine glands and their negative feedback mechanisms feedback mechanisms Example: under severe stress, the Example: under severe stress, the

hypothalamus and the sympathetic nervous hypothalamus and the sympathetic nervous system are activated system are activated As a result, body glucose levels rise As a result, body glucose levels rise

The Pituitary Gland and The Pituitary Gland and HypothalamusHypothalamus

The pituitary gland (hypophysis) has two The pituitary gland (hypophysis) has two major lobesmajor lobes

1.1. Posterior pituitary (lobe):Posterior pituitary (lobe):Pituicytes (glial-like supporting cells) and nerve Pituicytes (glial-like supporting cells) and nerve

fibersfibers

2.2. Anterior pituitary (lobe) (adenohypophysis)Anterior pituitary (lobe) (adenohypophysis)Glandular tissue Glandular tissue

Pituitary-Hypothalamic Pituitary-Hypothalamic RelationshipsRelationships

Posterior lobePosterior lobe A downgrowth of hypothalamic neural tissueA downgrowth of hypothalamic neural tissue Neural connection to the hypothalamus Neural connection to the hypothalamus

(hypothalamic-hypophyseal tract)(hypothalamic-hypophyseal tract) Nuclei of the hypothalamus synthesize the Nuclei of the hypothalamus synthesize the

neurohormones oxytocin and antidiuretic neurohormones oxytocin and antidiuretic hormone (ADH)hormone (ADH)

Neurohormones are transported to the Neurohormones are transported to the posterior pituitaryposterior pituitary

Pituitary-Hypothalamic Pituitary-Hypothalamic RelationshipsRelationships

Anterior Lobe:Anterior Lobe:Originates as an out-pocketing of the oral Originates as an out-pocketing of the oral

mucosamucosaHypophyseal portal systemHypophyseal portal system

Carries releasing and inhibiting hormones Carries releasing and inhibiting hormones to the anterior pituitary to regulate to the anterior pituitary to regulate hormone secretionhormone secretion

Anterior Pituitary Anterior Pituitary HormonesHormones

Growth hormone (GH)Growth hormone (GH)

Thyroid-stimulating hormone (TSH) or Thyroid-stimulating hormone (TSH) or thyrotropinthyrotropin

Adrenocorticotropic hormone (ACTH)Adrenocorticotropic hormone (ACTH)

Follicle-stimulating hormone (FSH)Follicle-stimulating hormone (FSH)

Luteinizing hormone (LH)Luteinizing hormone (LH)

Prolactin (PRL)Prolactin (PRL)

Anterior Pituitary Anterior Pituitary HormonesHormones

All are proteinsAll are proteins

All except GH activate cyclic AMP second-All except GH activate cyclic AMP second-messenger systems at their targetsmessenger systems at their targets

TSH, ACTH, FSH, and LH are all tropic TSH, ACTH, FSH, and LH are all tropic hormones (regulate the secretory action of hormones (regulate the secretory action of other endocrine glands)other endocrine glands)

Growth Hormone (GH)Growth Hormone (GH)

Produced by somatotrophs Produced by somatotrophs

Stimulates most cells, but targets bone and Stimulates most cells, but targets bone and skeletal muscleskeletal muscle

Promotes protein synthesis and encourages Promotes protein synthesis and encourages use of fats for fueluse of fats for fuel

Most effects are mediated indirectly by Most effects are mediated indirectly by insulin-like growth factors (IGFs)insulin-like growth factors (IGFs)

Growth Hormone (GH)Growth Hormone (GH)

GH release is regulated byGH release is regulated by Growth hormone–releasing hormone (GHRH) Growth hormone–releasing hormone (GHRH) Growth hormone–inhibiting hormone (GHIH) Growth hormone–inhibiting hormone (GHIH)

(somatostatin)(somatostatin)

Actions of Growth Actions of Growth HormoneHormone

Direct action of GHDirect action of GH Stimulates liver, skeletal muscle, bone, and Stimulates liver, skeletal muscle, bone, and

cartilage to produce insulin-like growth factorscartilage to produce insulin-like growth factors Mobilizes fats, elevates blood glucose by Mobilizes fats, elevates blood glucose by

decreasing glucose uptake and encouraging decreasing glucose uptake and encouraging glycogen breakdown (anti-insulin effect of GH)glycogen breakdown (anti-insulin effect of GH)

Homeostatic Homeostatic Imbalances of Growth Imbalances of Growth

HormoneHormone HypersecretionHypersecretion

In children results in gigantismIn children results in gigantism In adults results in acromegalyIn adults results in acromegaly

HyposecretionHyposecretion In children results in pituitary dwarfismIn children results in pituitary dwarfism


Growth hormone

Feedback Inhibits GHRH releaseStimulates GHIHreleaseInhibits GH synthesisand release

Anteriorpituitary

Liver andother tissues

Indirect actions(growth-promoting)

Direct actions(metabolic,anti-insulin)

Insulin-like growthfactors (IGFs)

ExtraskeletalSkeletal FatCarbohydratemetabolism

Increased cartilageformation and

skeletal growth

Increased proteinsynthesis, andcell growth and

proliferation

Increasedfat breakdown

and release

Increased bloodglucose and otheranti-insulin effects

EffectsEffects

Produce

Hypothalamussecretes growthhormone—releasinghormone (GHRH), andsomatostatin (GHIH)

Initial stimulus

Physiological response

Result

Increases, stimulates

Reduces, inhibits

Thyroid-Stimulating Thyroid-Stimulating Hormone (Thyrotropin)Hormone (Thyrotropin)

Produced by thyrotrophs of the anterior Produced by thyrotrophs of the anterior pituitarypituitary

Stimulates the normal development and Stimulates the normal development and secretory activity of the thyroidsecretory activity of the thyroid

Thyroid-Stimulating Thyroid-Stimulating Hormone (Thyrotropin)Hormone (Thyrotropin)

Regulation of TSH releaseRegulation of TSH release Stimulated by thyrotropin-releasing hormone Stimulated by thyrotropin-releasing hormone

(TRH)(TRH) Inhibited by rising blood levels of thyroid Inhibited by rising blood levels of thyroid

hormones that act on the pituitary and hormones that act on the pituitary and hypothalamus hypothalamus


Hypothalamus

Anterior pituitary

Thyroid gland

Thyroidhormones

TSH

TRH

Target cellsStimulates

Inhibits

Adrenocorticotropic Adrenocorticotropic Hormone Hormone

(Corticotropin)(Corticotropin) Secreted by corticotrophs of the anterior Secreted by corticotrophs of the anterior

pituitarypituitary

Stimulates the adrenal cortex to release Stimulates the adrenal cortex to release corticosteroidscorticosteroids

Adrenocorticotropic Adrenocorticotropic Hormone Hormone

(Corticotropin)(Corticotropin) Regulation of ACTH releaseRegulation of ACTH release

Triggered by hypothalamic corticotropin-Triggered by hypothalamic corticotropin-releasing hormone (CRH) in a daily rhythmreleasing hormone (CRH) in a daily rhythm

Internal and external factors such as fever, Internal and external factors such as fever, hypoglycemia, and stressors can alter the hypoglycemia, and stressors can alter the release of CRHrelease of CRH

GonadotropinsGonadotropins

Follicle-stimulating hormone (FSH) and Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)luteinizing hormone (LH)

Secreted by gonadotrophs of the anterior Secreted by gonadotrophs of the anterior pituitarypituitary

FSH stimulates gamete (egg or sperm) FSH stimulates gamete (egg or sperm) productionproduction

LH promotes production of gonadal hormonesLH promotes production of gonadal hormones

Absent from the blood in prepubertal boys Absent from the blood in prepubertal boys and girlsand girls

GonadotropinsGonadotropins

Regulation of gonadotropin releaseRegulation of gonadotropin release Triggered by the gonadotropin-releasing Triggered by the gonadotropin-releasing

hormone (GnRH) during and after pubertyhormone (GnRH) during and after puberty Suppressed by gonadal hormones (feedback)Suppressed by gonadal hormones (feedback)


Secreted by lactotrophs of the anterior Secreted by lactotrophs of the anterior pituitarypituitary

Stimulates milk productionStimulates milk production


Regulation of PRL releaseRegulation of PRL release Primarily controlled by prolactin-inhibiting Primarily controlled by prolactin-inhibiting

hormone (PIH) (dopamine)hormone (PIH) (dopamine)

Blood levels rise toward the end of pregnancyBlood levels rise toward the end of pregnancy

Suckling stimulates PRH release and Suckling stimulates PRH release and promotes continued milk productionpromotes continued milk production

The Posterior Pituitary The Posterior Pituitary

Contains axons of hypothalamic neuronsContains axons of hypothalamic neurons

Stores antidiuretic hormone (ADH) and Stores antidiuretic hormone (ADH) and oxytocinoxytocin

ADH and oxytocin are released in response to ADH and oxytocin are released in response to nerve impulsesnerve impulses

Both use PIP-calcium second-messenger Both use PIP-calcium second-messenger mechanism at their targetsmechanism at their targets

OxytocinOxytocin

Stimulates uterine contractions during Stimulates uterine contractions during childbirth by mobilizing Cachildbirth by mobilizing Ca2+2+ through a PIP through a PIP22--CaCa2+2+ second-messenger system second-messenger system

Also triggers milk ejection (“letdown” reflex) Also triggers milk ejection (“letdown” reflex) in women producing milkin women producing milk

Plays a role in sexual arousal and orgasm in Plays a role in sexual arousal and orgasm in males and femalesmales and females

Antidiuretic Hormone Antidiuretic Hormone (ADH)(ADH)

Hypothalamic osmoreceptors respond to Hypothalamic osmoreceptors respond to changes in the solute concentration of the changes in the solute concentration of the bloodblood

If solute concentration is highIf solute concentration is high Osmoreceptors depolarize and transmit Osmoreceptors depolarize and transmit

impulses to hypothalamic neuronsimpulses to hypothalamic neurons ADH is synthesized and released, inhibiting ADH is synthesized and released, inhibiting

urine formationurine formation

Antidiuretic Hormone Antidiuretic Hormone (ADH)(ADH)

If solute concentration is lowIf solute concentration is low ADH is not released, allowing water loss ADH is not released, allowing water loss

Alcohol inhibits ADH release and causes Alcohol inhibits ADH release and causes copious urine outputcopious urine output

Homeostatic Homeostatic Imbalances of ADHImbalances of ADH

ADH deficiency—diabetes insipidus; huge ADH deficiency—diabetes insipidus; huge output of urine and intense thirstoutput of urine and intense thirst

ADH hypersecretion (after neurosurgery, ADH hypersecretion (after neurosurgery, trauma, or secreted by cancer cells)—trauma, or secreted by cancer cells)—syndrome of inappropriate ADH secretion syndrome of inappropriate ADH secretion (SIADH)(SIADH)

Thyroid GlandThyroid Gland

Consists of two lateral lobes connected by a Consists of two lateral lobes connected by a median mass called the isthmusmedian mass called the isthmus

Composed of follicles that produce the Composed of follicles that produce the glycoprotein thyroglobulinglycoprotein thyroglobulin

Colloid (thyroglobulin + iodine) fills the lumen Colloid (thyroglobulin + iodine) fills the lumen of the follicles and is the precursor of thyroid of the follicles and is the precursor of thyroid hormonehormone

Parafollicular cells produce the hormone Parafollicular cells produce the hormone calcitonincalcitonin

Figure 16.8

Thyroid Hormone (TH)Thyroid Hormone (TH)

Actually two related compoundsActually two related compounds TT44 (thyroxine); has 2 tyrosine molecules + 4 (thyroxine); has 2 tyrosine molecules + 4

bound iodine atomsbound iodine atoms TT33 (triiodothyronine); has 2 tyrosines + 3 bound (triiodothyronine); has 2 tyrosines + 3 bound

iodine atomsiodine atoms

Thyroid HormoneThyroid Hormone

Major metabolic hormoneMajor metabolic hormone

Increases metabolic rate and heat production Increases metabolic rate and heat production (calorigenic effect)(calorigenic effect)

Plays a role inPlays a role in Maintenance of blood pressureMaintenance of blood pressure Regulation of tissue growthRegulation of tissue growth Development of skeletal and nervous systemsDevelopment of skeletal and nervous systems Reproductive capabilitiesReproductive capabilities

Figure 16.9

To peripheral tissues

T3

T3

T3

T4

T4

Lysosome

Tyrosines (part of thyroglobulinmolecule)

T4

DIT (T2)Iodine

MIT (T1)

Thyro-globulincolloid

Iodide (I–)

RoughER

Capillary

Colloid

Colloid inlumen offollicle

Thyroid follicle cells

Iodinated tyrosines arelinked together to form T3

and T4.

Iodideis oxidizedto iodine.

Thyroglobulin colloid isendocytosed and combinedwith a lysosome.

Lysosomal enzymes cleaveT4 and T3 from thyroglobulincolloid and hormones diffuseinto bloodstream.

Iodide (I–) is trapped(actively transported in).

Thyroglobulin is synthesized anddischarged into the follicle lumen.

Iodine is attached to tyrosinein colloid, forming DIT and MIT.

Golgiapparatus

1

2

3

4

5

6

7

Transport and Transport and Regulation of THRegulation of TH

TT44 and T and T33 are transported by thyroxine- are transported by thyroxine-binding globulins (TBGs) binding globulins (TBGs)

Both bind to target receptors, but TBoth bind to target receptors, but T33 is ten is ten times more active than Ttimes more active than T44

Peripheral tissues convert TPeripheral tissues convert T44 to T to T33

Transport and Transport and Regulation of THRegulation of TH

Negative feedback regulation of TH release Negative feedback regulation of TH release Rising TH levels provide negative feedback Rising TH levels provide negative feedback

inhibition on release of TSHinhibition on release of TSH Hypothalamic thyrotropin-releasing hormone Hypothalamic thyrotropin-releasing hormone

(TRH) can overcome the negative feedback (TRH) can overcome the negative feedback during pregnancy or exposure to coldduring pregnancy or exposure to cold

Figure 16.7

Hypothalamus

Anterior pituitary

Thyroid gland

Thyroidhormones

TSH

TRH

Target cellsStimulates

Inhibits

Homeostatic Homeostatic Imbalances of THImbalances of TH

Hyposecretion in adults—myxedema; Hyposecretion in adults—myxedema; endemic goiter if due to lack of iodineendemic goiter if due to lack of iodine

Hyposecretion in infants—cretinismHyposecretion in infants—cretinism

Hypersecretion—Graves’ diseaseHypersecretion—Graves’ disease

Figure 16.10

CalcitoninCalcitonin

Produced by parafollicular (C) cellsProduced by parafollicular (C) cells

Antagonist to parathyroid hormone (PTH)Antagonist to parathyroid hormone (PTH)

Inhibits osteoclast activity and release of CaInhibits osteoclast activity and release of Ca2+2+ from bone matrixfrom bone matrix

CalcitoninCalcitonin

Stimulates CaStimulates Ca2+2+ uptake and incorporation into uptake and incorporation into bone matrixbone matrix

Regulated by a humoral (CaRegulated by a humoral (Ca2+2+ concentration concentration in the blood) negative feedback mechanismin the blood) negative feedback mechanism

No important role in humans; removal of No important role in humans; removal of thyroid (and its C cells) does not affect Cathyroid (and its C cells) does not affect Ca2+2+ homeostasishomeostasis

Parathyroid GlandsParathyroid Glands

Four to eight tiny glands embedded in the Four to eight tiny glands embedded in the posterior aspect of the thyroidposterior aspect of the thyroid

Contain oxyphil cells (function unknown) and Contain oxyphil cells (function unknown) and chief cells that secrete parathyroid hormone chief cells that secrete parathyroid hormone (PTH) or parathormone(PTH) or parathormone

PTH—most important hormone in CaPTH—most important hormone in Ca2+2+ homeostasishomeostasis

Figure 16.11

(b)

Capillary

Chiefcells(secreteparathyroidhormone)Oxyphilcells

Pharynx(posterioraspect)

Thyroidgland

Parathyroidglands

Trachea

Esophagus

(a)

Parathyroid HormoneParathyroid Hormone

FunctionsFunctions Stimulates osteoclasts to digest bone matrix Stimulates osteoclasts to digest bone matrix Enhances reabsorption of CaEnhances reabsorption of Ca2+2+ and secretion of and secretion of

phosphate by the kidneysphosphate by the kidneys Promotes activation of vitamin D (by the Promotes activation of vitamin D (by the

kidneys); increases absorption of Cakidneys); increases absorption of Ca2+2+ by by intestinal mucosaintestinal mucosa

Negative feedback control: rising CaNegative feedback control: rising Ca2+2+ in the in the blood inhibits PTH release blood inhibits PTH release

Figure 16.12

Intestine

Kidney

Bloodstream

Hypocalcemia (low blood Ca2+) stimulatesparathyroid glands to release PTH.

Rising Ca2+ inblood inhibitsPTH release.

1 PTH activatesosteoclasts: Ca2+

and PO43S released

into blood.

2 PTH increasesCa2+ reabsorptionin kidneytubules.

3 PTH promoteskidney’s activation of vitamin D,which increases Ca2+ absorptionfrom food.

Bone

Ca2+ ions

PTH Molecules

Homeostatic Homeostatic Imbalances of PTHImbalances of PTH

Hyperparathyroidism due to tumorHyperparathyroidism due to tumor Bones soften and deformBones soften and deform Elevated CaElevated Ca2+2+ depresses the nervous system depresses the nervous system

and contributes to formation of kidney stonesand contributes to formation of kidney stones

Hypoparathyroidism following gland trauma Hypoparathyroidism following gland trauma or removalor removal Results in tetany, respiratory paralysis, and Results in tetany, respiratory paralysis, and

deathdeath

Adrenal (Suprarenal) Adrenal (Suprarenal) GlandsGlands

Paired, pyramid-shaped organs atop the Paired, pyramid-shaped organs atop the kidneyskidneys

Structurally and functionally, they are two Structurally and functionally, they are two glands in oneglands in one Adrenal medulla—nervous tissue; part of the Adrenal medulla—nervous tissue; part of the

sympathetic nervous systemsympathetic nervous system Adrenal cortex—three layers of glandular tissue Adrenal cortex—three layers of glandular tissue

that synthesize and secrete corticosteroidsthat synthesize and secrete corticosteroids

Adrenal CortexAdrenal Cortex

Three layers and the corticosteroids producedThree layers and the corticosteroids produced Zona glomerulosa—mineralocorticoidsZona glomerulosa—mineralocorticoids Zona fasciculata—glucocorticoidsZona fasciculata—glucocorticoids Zona reticularis—sex hormones, or Zona reticularis—sex hormones, or

gonadocorticoidsgonadocorticoids

Figure 16.13a

• Cortex

Kidney

• Medulla

Adrenal gland

Capsule

Zonaglomerulosa

Zonafasciculata

Zonareticularis

Adrenalmedulla

(a) Drawing of the histology of the adrenal cortex and a portion of the adrenal medulla

Med

ulla

Cort

ex

MineralocorticoidsMineralocorticoids

Regulate electrolytes (primarily NaRegulate electrolytes (primarily Na++ and K and K++) in ) in ECFECF Importance of NaImportance of Na++: affects ECF volume, blood : affects ECF volume, blood

volume, blood pressure, levels of other ionsvolume, blood pressure, levels of other ions Importance of KImportance of K++: sets RMP of cells: sets RMP of cells

Aldosterone is the most potent Aldosterone is the most potent mineralocorticoid mineralocorticoid Stimulates NaStimulates Na++ reabsorption and water reabsorption and water

retention by the kidneysretention by the kidneys

Mechanisms of Mechanisms of Aldosterone SecretionAldosterone Secretion

1.1. Renin-angiotensin mechanism: decreased Renin-angiotensin mechanism: decreased blood pressure stimulates kidneys to release blood pressure stimulates kidneys to release renin, triggers formation of angiotensin II, a renin, triggers formation of angiotensin II, a potent stimulator of aldosterone release potent stimulator of aldosterone release

2.2. Plasma concentration of KPlasma concentration of K++: Increased K: Increased K++ directly influences the zona glomerulosa cells directly influences the zona glomerulosa cells to release aldosteroneto release aldosterone

3.3. ACTH: causes small increases of aldosterone ACTH: causes small increases of aldosterone during stressduring stress

4.4. Atrial natriuretic peptide (ANP): blocks renin Atrial natriuretic peptide (ANP): blocks renin and aldosterone secretion, to decrease blood and aldosterone secretion, to decrease blood pressurepressure

Figure 16.14

Primary regulators Other factors

Blood volumeand/or blood

pressure

Angiotensin II

Blood pressureand/or blood

volume

K+ in blood

DirectstimulatingeffectRenin

Initiatescascadethatproduces

Kidney

Hypo-thalamus

Heart

CRH

Anteriorpituitary

Zona glomerulosaof adrenal cortex

Enhancedsecretionof aldosterone

Targetskidney tubules

Absorption of Na+ andwater; increased K+ excretion

Blood volumeand/or blood pressure

Inhibitoryeffect

Stress

ACTH Atrial natriureticpeptide (ANP)

Homeostatic Homeostatic Imbalances of Imbalances of AldosteroneAldosterone

Aldosteronism—hypersecretion due to Aldosteronism—hypersecretion due to adrenal tumorsadrenal tumors Hypertension and edema due to excessive NaHypertension and edema due to excessive Na++

Excretion of KExcretion of K++ leading to abnormal function of leading to abnormal function of neurons and muscle neurons and muscle

Glucocorticoids Glucocorticoids (Cortisol)(Cortisol)

Keep blood sugar levels relatively constantKeep blood sugar levels relatively constant

Maintain blood pressure by increasing the Maintain blood pressure by increasing the action of vasoconstrictorsaction of vasoconstrictors

Glucocorticoids Glucocorticoids (Cortisol)(Cortisol)

Cortisol is the most significant glucocorticoidCortisol is the most significant glucocorticoid Released in response to ACTH, patterns of Released in response to ACTH, patterns of

eating and activity, and stresseating and activity, and stress Prime metabolic effect is gluconeogenesis—Prime metabolic effect is gluconeogenesis—

formation of glucose from fats and proteinsformation of glucose from fats and proteins Promotes rises in blood glucose, fatty acids, Promotes rises in blood glucose, fatty acids,

and amino acidsand amino acids

Homeostatic Homeostatic Imbalances of Imbalances of

GlucocorticoidsGlucocorticoidsHypersecretion—Cushing’s syndromeHypersecretion—Cushing’s syndrome

Depresses cartilage and bone formationDepresses cartilage and bone formation Inhibits inflammationInhibits inflammationDepresses the immune systemDepresses the immune systemPromotes changes in cardiovascular, Promotes changes in cardiovascular,

neural, and gastrointestinal functionneural, and gastrointestinal function

Hyposecretion—Addison’s diseaseHyposecretion—Addison’s diseaseAlso involves deficits in mineralocorticoidsAlso involves deficits in mineralocorticoids

Decrease in glucose and NaDecrease in glucose and Na++ levels levels Weight loss, severe dehydration, and Weight loss, severe dehydration, and

hypotensionhypotension

Figure 16.15

Gonadocorticoids (Sex Gonadocorticoids (Sex Hormones)Hormones)

Most are androgens (male sex hormones) that Most are androgens (male sex hormones) that are converted to testosterone in tissue cells are converted to testosterone in tissue cells or estrogens in femalesor estrogens in females

May contribute toMay contribute to The onset of pubertyThe onset of puberty The appearance of secondary sex The appearance of secondary sex

characteristicscharacteristics Sex drive Sex drive

Adrenal MedullaAdrenal Medulla

Chromaffin cells secrete epinephrine (80%) Chromaffin cells secrete epinephrine (80%) and norepinephrine (20%)and norepinephrine (20%)

These hormones causeThese hormones cause Blood glucose levels to riseBlood glucose levels to rise Blood vessels to constrictBlood vessels to constrict The heart to beat fasterThe heart to beat faster Blood to be diverted to the brain, heart, and Blood to be diverted to the brain, heart, and

skeletal muscleskeletal muscle

Adrenal MedullaAdrenal Medulla

Epinephrine stimulates metabolic activities, Epinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal bronchial dilation, and blood flow to skeletal muscles and the heartmuscles and the heart

Norepinephrine influences peripheral Norepinephrine influences peripheral vasoconstriction and blood pressurevasoconstriction and blood pressure

Figure 16.16

Short-term stress More prolonged stress

Stress

Hypothalamus

CRH (corticotropin-releasing hormone)

Corticotroph cellsof anterior pituitary

To target in blood

Adrenal cortex(secretes steroidhormones)

GlucocorticoidsMineralocorticoids

ACTH

Catecholamines(epinephrine andnorepinephrine)

Short-term stress response

1. Increased heart rate2. Increased blood pressure3. Liver converts glycogen to glucose and releases glucose to blood4. Dilation of bronchioles5. Changes in blood flow patterns leading to decreased digestive system activity and reduced urine output6. Increased metabolic rate

Long-term stress response

1. Retention of sodium and water by kidneys2. Increased blood volume and blood pressure

1. Proteins and fats converted to glucose or broken down for energy2. Increased blood glucose3. Suppression of immune system

Adrenal medulla(secretes amino acid-based hormones)

Preganglionicsympatheticfibers

Spinal cord

Nerve impulses

Pineal GlandPineal Gland

Small gland hanging from the roof of the Small gland hanging from the roof of the third ventricle third ventricle

Pinealocytes secrete melatonin, derived Pinealocytes secrete melatonin, derived from serotoninfrom serotonin

Melatonin may affectMelatonin may affectTiming of sexual maturation and pubertyTiming of sexual maturation and pubertyDay/night cyclesDay/night cyclesPhysiological processes that show rhythmic Physiological processes that show rhythmic

variations (body temperature, sleep, variations (body temperature, sleep, appetite)appetite)

PancreasPancreas

Triangular gland behind the stomachTriangular gland behind the stomach

Has both exocrine and endocrine cellsHas both exocrine and endocrine cellsAcinar cells (exocrine) produce an enzyme-Acinar cells (exocrine) produce an enzyme-

rich juice for digestionrich juice for digestionPancreatic islets (islets of Langerhans) Pancreatic islets (islets of Langerhans)

contain endocrine cellscontain endocrine cells Alpha (Alpha () cells produce glucagon (a ) cells produce glucagon (a

hyperglycemic hormone)hyperglycemic hormone) Beta (Beta () cells produce insulin (a ) cells produce insulin (a

hypoglycemic hormone)hypoglycemic hormone)

Figure 16.17

Pancreaticislet (ofLangerhans)

• (Glucagon- producing) cells

• (Insulin- producing) cells

Pancreaticacinarcells (exocrine)

GlucagonGlucagon

Major target is the liver, where it promotesMajor target is the liver, where it promotes Glycogenolysis—breakdown of glycogen to Glycogenolysis—breakdown of glycogen to

glucoseglucose Gluconeogenesis—synthesis of glucose from Gluconeogenesis—synthesis of glucose from

lactic acid and noncarbohydrateslactic acid and noncarbohydrates Release of glucose to the blood Release of glucose to the blood

InsulinInsulin

Effects of insulinEffects of insulin Lowers blood glucose levelsLowers blood glucose levels Enhances membrane transport of glucose into Enhances membrane transport of glucose into

fat and muscle cellsfat and muscle cells Participates in neuronal development and Participates in neuronal development and

learning and memorylearning and memory Inhibits glycogenolysis and gluconeogenesisInhibits glycogenolysis and gluconeogenesis

Insulin Action on CellsInsulin Action on Cells

Activates a tyrosine kinase enzyme receptorActivates a tyrosine kinase enzyme receptor

Cascade leads to increased glucose uptake Cascade leads to increased glucose uptake and enzymatic activities thatand enzymatic activities that Catalyze the oxidation of glucose for ATP Catalyze the oxidation of glucose for ATP

productionproduction Polymerize glucose to form glycogenPolymerize glucose to form glycogen Convert glucose to fat (particularly in adipose Convert glucose to fat (particularly in adipose

tissue)tissue)

Figure 16.18

Liver

Liver

Tissue cells

Stimulates glucose uptake by cells

StimulatesglycogenformationPancreas

Pancreas

Insulin

Bloodglucosefalls tonormalrange.

Stimulatesglycogenbreakdown

Bloodglucoserises tonormalrange.

Glucagon

Stimulus Bloodglucose level

Stimulus Bloodglucose level

GlycogenGlucose

GlycogenGlucose

Homeostatic Homeostatic Imbalances of InsulinImbalances of Insulin

Diabetes mellitus (DM)Diabetes mellitus (DM)Due to hyposecretion or hypoactivity of insulinDue to hyposecretion or hypoactivity of insulinThree cardinal signs of DMThree cardinal signs of DM

Polyuria—huge urine outputPolyuria—huge urine output Polydipsia—excessive thirstPolydipsia—excessive thirst Polyphagia—excessive hunger and food Polyphagia—excessive hunger and food

consumptionconsumption

Hyperinsulinism:Hyperinsulinism:Excessive insulin secretion; results in Excessive insulin secretion; results in

hypoglycemia, disorientation, unconsciousnesshypoglycemia, disorientation, unconsciousness

Table 16.4

Ovaries and PlacentaOvaries and Placenta

Gonads produce steroid sex hormonesGonads produce steroid sex hormones

Ovaries produce estrogens and Ovaries produce estrogens and progesterone responsible for:progesterone responsible for:Maturation of female reproductive organsMaturation of female reproductive organsAppearance of female secondary sexual Appearance of female secondary sexual

characteristics characteristics Breast development and cyclic changes in Breast development and cyclic changes in

the uterine mucosathe uterine mucosa

The placenta secretes estrogens, The placenta secretes estrogens, progesterone, and human chorionic progesterone, and human chorionic gonadotropin (hCG)gonadotropin (hCG)

Testes Testes

Testes produce testosterone thatTestes produce testosterone that Initiates maturation of male reproductive Initiates maturation of male reproductive

organsorgans Causes appearance of male secondary sexual Causes appearance of male secondary sexual

characteristics and sex drivecharacteristics and sex drive Is necessary for normal sperm productionIs necessary for normal sperm production Maintains reproductive organs in their Maintains reproductive organs in their

functional statefunctional state

Other Hormone-Other Hormone-Producing StructuresProducing Structures

HeartHeart Atrial natriuretic peptide (ANP) reduces blood Atrial natriuretic peptide (ANP) reduces blood

pressure, blood volume, and blood Napressure, blood volume, and blood Na++ concentrationconcentration

Gastrointestinal tract enteroendocrine cellsGastrointestinal tract enteroendocrine cells Gastrin stimulates release of HClGastrin stimulates release of HCl Secretin stimulates liver and pancreasSecretin stimulates liver and pancreas Cholecystokinin stimulates pancreas, Cholecystokinin stimulates pancreas,

gallbladder, and hepatopancreatic sphinctergallbladder, and hepatopancreatic sphincter


KidneysKidneysErythropoietin signals production of red Erythropoietin signals production of red

blood cellsblood cellsRenin initiates the renin-angiotensin Renin initiates the renin-angiotensin

mechanismmechanism

SkinSkinCholecalciferol, the precursor of vitamin DCholecalciferol, the precursor of vitamin D

Adipose tissueAdipose tissueLeptin is involved in appetite control, and Leptin is involved in appetite control, and

stimulates increased energy expenditurestimulates increased energy expenditure


Skeleton (osteoblasts)Skeleton (osteoblasts) Osteocalcin prods pancreatic beta cells to Osteocalcin prods pancreatic beta cells to

divide and secrete more insulin, improving divide and secrete more insulin, improving glucose handling and reducing body fatglucose handling and reducing body fat

ThymusThymus Thymulin, thymopoietins, and thymosins are Thymulin, thymopoietins, and thymosins are

involved in normal the development of the T involved in normal the development of the T lymphocytes in the immune response lymphocytes in the immune response

Developmental Aspects Developmental Aspects

Hormone-producing glands arise from all Hormone-producing glands arise from all three germ layers three germ layers

Exposure to pesticides, industrial chemicals, Exposure to pesticides, industrial chemicals, arsenic, dioxin, and soil and water pollutants arsenic, dioxin, and soil and water pollutants disrupts hormone functiondisrupts hormone function

Sex hormones, thyroid hormone, and Sex hormones, thyroid hormone, and glucocorticoids are vulnerable to the effects glucocorticoids are vulnerable to the effects of pollutantsof pollutants

Interference with glucocorticoids may help Interference with glucocorticoids may help explain high cancer rates in certain areasexplain high cancer rates in certain areas

Developmental AspectsDevelopmental Aspects

Ovaries undergo significant changes with age Ovaries undergo significant changes with age and become unresponsive to gonadotropins; and become unresponsive to gonadotropins; problems associated with estrogen deficiency problems associated with estrogen deficiency begin to occurbegin to occur

Testosterone also diminishes with age, but Testosterone also diminishes with age, but effect is not usually seen until very old ageeffect is not usually seen until very old age

Developmental AspectsDevelopmental Aspects

GH levels decline with age and this accounts GH levels decline with age and this accounts for muscle atrophy with agefor muscle atrophy with age

TH declines with age, contributing to lower TH declines with age, contributing to lower basal metabolic ratesbasal metabolic rates

PTH levels remain fairly constant with age, PTH levels remain fairly constant with age, but lack of estrogen in older women makes but lack of estrogen in older women makes them more vulnerable to bone-demineralizing them more vulnerable to bone-demineralizing effects of PTHeffects of PTH

Documents

16 The Endocrine System:. Endocrine System: Overview Acts with the nervous system to coordinate and integrate the activity of body cells Acts with the