Endocrine System: OverviewEndocrine System: Overview

Endocrine system – the body’s second great Endocrine system – the body’s second great controlling system which influences metabolic controlling system which influences metabolic activities of cells by means of hormones activities of cells by means of hormones

Endocrine glands – pituitary, thyroid, Endocrine glands – pituitary, thyroid, parathyroid, adrenal, pineal, and thymus parathyroid, adrenal, pineal, and thymus

The pancreas and gonads produce both The pancreas and gonads produce both hormones and exocrine productshormones and exocrine products

Endocrine System: OverviewEndocrine System: Overview

The hypothalamus has both neural functions The hypothalamus has both neural functions and releases hormonesand releases hormones

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

Major Endocrine OrgansMajor Endocrine Organs

Figure 16.1

Autocrines and ParacrinesAutocrines and Paracrines

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 themaffect cells other than those that secrete them

These are not considered hormones since These are not considered hormones since hormones are long-distance chemical signalshormones are long-distance chemical signals

HormonesHormones

Hormones – chemical substances secreted by Hormones – chemical substances secreted by cells into the extracellular fluidscells into the extracellular fluids Regulate the metabolic function of other cellsRegulate the metabolic function of other cells Have lag times ranging from seconds to hoursHave lag times ranging from seconds to hours Tend to have prolonged effectsTend to have prolonged effects Are classified as amino acid-based hormones, or Are classified as amino acid-based hormones, or

steroidssteroids Eicosanoids – biologically active lipids with Eicosanoids – biologically active lipids with

local hormone–like activitylocal hormone–like activity

Types of HormonesTypes of Hormones

Amino acid basedAmino acid based Amines, thyroxine, peptide, and protein hormonesAmines, thyroxine, peptide, and protein hormones

Steroids – gonadal and adrenocortical Steroids – gonadal and adrenocortical hormones, and hormones from the kidneyshormones, and hormones from the kidneys Remain in the blood stream longer because they Remain in the blood stream longer because they

are bound to proteinsare bound to proteins Eicosanoids – leukotrienes and prostaglandinsEicosanoids – leukotrienes and prostaglandins

Are derived from lipidsAre derived from lipids

Hormone ActionHormone Action Hormones alter target cell activity by one of Hormones alter target cell activity by one of

two mechanismstwo mechanisms Second messengers:Second messengers:

Regulatory G proteinsRegulatory G proteins Amino acid–based hormonesAmino acid–based hormones

Direct gene activationDirect gene activation Steroid hormonesSteroid hormones

The precise response depends on the type of The precise response depends on the type of the target cellthe target cell

Mechanism of Hormone ActionMechanism of Hormone Action

Hormones produce one or more of the Hormones produce one or more of the following cellular changes in target cellsfollowing cellular changes in target cells Alter plasma membrane permeability Alter plasma membrane permeability Stimulate protein synthesis Stimulate protein synthesis Activate or deactivate enzyme systemsActivate or deactivate enzyme systems Induce secretory activityInduce secretory activity Stimulate mitosisStimulate mitosis

Amino Acid-Based Hormone Action: Amino Acid-Based Hormone Action:

cAMP Second MessengercAMP Second Messenger Hormone (first messenger) binds to a receptorHormone (first messenger) binds to a receptor Hormone binds to a G proteinHormone binds to a G protein The G protein is activated as it binds to GTP, which The G protein is activated as it binds to GTP, which

displaces GDPdisplaces GDP Activated G protein activates the effector enzyme Activated G protein activates the effector enzyme

adenylate cyclaseadenylate cyclase Adenylate cyclase generates cAMP (second Adenylate cyclase generates cAMP (second

messenger) from existing ATPmessenger) from existing ATP cAMP activates protein kinases (cause cellular cAMP activates protein kinases (cause cellular

effects)effects)

Receptor

Hormone A

ReceptorGTP GTP

GTP GTP GTP GTP

ATP cAMP

Inactive protein kinase A

Active protein kinase A

CatecholaminesACTHFSHLHGlucagonPTHTSHCalcitonin

Triggers responses of targetcell (activates enzymes,stimulates cellularsecretion, opens ionchannels, etc.)

Adenylate cyclase Hormone B

GDPGDP

Extracellular fluid

Cytoplasm

Gs Gi

1

2 34

3 2

1

5

Figure 16.2

Amino Acid-Based Hormone Action: Amino Acid-Based Hormone Action: cAMP Second MessengercAMP Second Messenger

Hormone binds to the receptor and activates Hormone binds to the receptor and activates G proteinG protein

G protein binds and activates phospholipase G protein binds and activates phospholipase Phospholipase splits the phospholipid PIPPhospholipase splits the phospholipid PIP22 into into

diacylglycerol (DAG) and IPdiacylglycerol (DAG) and IP33 (both are second (both are second messengers)messengers)

DAG activates protein kinases DAG activates protein kinases IPIP33 triggers release of Ca triggers release of Ca2+2+ stores stores CaCa2+2+ (third messenger) alters responses at the (third messenger) alters responses at the

cellular levelcellular level

Amino Acid-Based Hormone Action: Amino Acid-Based Hormone Action:

PIP-CalciumPIP-Calcium

GTP PIP2

IP3

ReceptorGTP

GTP

CatecholaminesTRHADHGnRHOxytocin

Triggers responses of target cell

GDP

Extracellular fluid

Cytoplasm

Inactiveprotein kinase C

Activeprotein kinase C

Phospholipase C

Gq

Ca2+ Ca2+- calmodulin

Hormone

Endoplasmicreticulum

DAG1

2 34 5

5

6

Figure 16.3

Amino Acid-Based Hormone Action: Amino Acid-Based Hormone Action:

PIP MechanismPIP Mechanism

Steroid HormonesSteroid Hormones

This interaction prompts DNA transcription to This interaction prompts DNA transcription to produce mRNAproduce mRNA

The mRNA is translated into proteins, which The mRNA is translated into proteins, which bring about a cellular effectbring about a cellular effect

Steroidhormone

Steroidhormone

Cytoplasm

Receptor-chaperonincomplex

Molecularchaperones

Receptor-hormonecomplex

Hormoneresponseelements

Binding

Transcription

Chromatin

mRNA

Nucleus

New proteinTranslation

Ribosome

mRNA

Figure 16.4

Steroidhormone

Figure 16.4

Target Cell SpecificityTarget Cell Specificity

Hormones circulate to all tissues but only Hormones circulate to all tissues but only activate cells referred to as target cellsactivate cells referred to as target cells

Target cells must have specific receptors to Target cells must have specific receptors to which the hormone bindswhich the hormone binds

These receptors may be intracellular or located These receptors may be intracellular or located on the plasma membraneon the plasma membrane

Target Cell SpecificityTarget Cell Specificity

Examples of hormone activityExamples of hormone activity ACTH receptors are only found on certain cells of ACTH receptors are only found on certain cells of

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

the bodythe body

Target Cell ActivationTarget Cell Activation

Target cell activation depends on three factorsTarget cell activation depends on three factors Blood levels of the hormoneBlood levels of the hormone Relative number of receptors on the target cellRelative number of receptors on the target cell The affinity of those receptors for the hormoneThe affinity of those receptors for the hormone

Up-regulation – target cells form more Up-regulation – target cells form more receptors in response to less hormonereceptors in response to less hormone

Down-regulation – target cells lose receptors Down-regulation – target cells lose receptors in response to more hormonein response to more hormone

Hormone Concentrations in the Hormone Concentrations in the BloodBlood

Hormones circulate in the blood in two forms Hormones circulate in the blood in two forms – free or bound– free or bound Steroids and thyroid hormone are attached to Steroids and thyroid hormone are attached to

plasma proteinsplasma proteins All others are unencumbered and can easily move All others are unencumbered and can easily move

out of the bloodstream to bind to the appropriate out of the bloodstream to bind to the appropriate receptorsreceptors

Hormone Concentrations in the Hormone Concentrations in the BloodBlood

Concentrations of circulating hormone reflect: Concentrations of circulating hormone reflect: Rate of releaseRate of release Speed of inactivation and removal from the bodySpeed of inactivation and removal from the body

Hormones are removed from the blood by:Hormones are removed from the blood by: Degrading enzymes in the plasma or interstitial Degrading enzymes in the plasma or interstitial

fluidfluid The kidneysThe kidneys Liver enzyme systemsLiver enzyme systems

Interaction of Hormones at Interaction of Hormones at Target CellsTarget Cells

Three types of hormone interactionThree types of hormone interaction 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 the Synergism – more than one hormone produces the

same effects on a target cellsame effects on a target cell Antagonism – one or more hormones opposes the Antagonism – one or more hormones opposes the

action of another hormoneaction of another hormone

Control of Hormone ReleaseControl of Hormone Release

Blood levels of hormones: Blood 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 to:response to: Humoral stimuliHumoral stimuli Neural stimuliNeural stimuli Hormonal stimuliHormonal stimuli

Humoral StimuliHumoral Stimuli

Humoral stimuli – secretion of hormones in Humoral stimuli – secretion of hormones in direct response to changing blood levels of direct response to changing blood levels of ions and nutrientsions and nutrients

Example: concentration of calcium ions in the Example: concentration of calcium ions in the bloodblood Declining blood CaDeclining blood Ca2+2+ concentration stimulates the concentration stimulates the

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

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

Humoral StimuliHumoral Stimuli

Figure 16.5a

Neural StimuliNeural Stimuli

Neural stimuli – nerve Neural stimuli – nerve fibers stimulate fibers stimulate hormone releasehormone release Preganglionic Preganglionic

sympathetic nervous sympathetic nervous system (SNS) fibers system (SNS) fibers stimulate the adrenal stimulate the adrenal medulla to secrete medulla to secrete catecholamines catecholamines

Figure 16.5b

Hormonal StimuliHormonal Stimuli

Hormonal stimuli – release of hormones in Hormonal stimuli – release of hormones in response to hormones produced by other response to hormones produced by other endocrine organsendocrine organs The hypothalamic hormones stimulate the anterior The hypothalamic hormones stimulate the anterior

pituitary pituitary In turn, pituitary hormones stimulate targets to In turn, pituitary hormones stimulate targets to

secrete still more hormonessecrete still more hormones

Hormonal StimuliHormonal Stimuli

Figure 16.5c

Nervous System ModulationNervous System Modulation

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

Nervous System ModulationNervous System Modulation

The nervous system can override normal The nervous system can override normal endocrine controlsendocrine controls For example, control of blood glucose levelsFor example, control of blood glucose levels

Normally the endocrine system maintains blood glucose Normally the endocrine system maintains blood glucose Under stress, the body needs more glucose Under stress, the body needs more glucose The hypothalamus and the sympathetic nervous system The hypothalamus and the sympathetic nervous system

are activated to supply ample glucoseare activated to supply ample glucose

Major Endocrine Organs: Major Endocrine Organs: Pituitary (Hypophysis)Pituitary (Hypophysis)

Pituitary gland – two-lobed organ that secretes Pituitary gland – two-lobed organ that secretes nine major hormonesnine major hormones

Neurohypophysis – posterior lobe (neural Neurohypophysis – posterior lobe (neural tissue) and the infundibulumtissue) and the infundibulum Receives, stores, and releases hormones from the Receives, stores, and releases hormones from the

hypothalamushypothalamus Adenohypophysis – anterior lobe, made up of Adenohypophysis – anterior lobe, made up of

glandular tissue glandular tissue Synthesizes and secretes a number of hormonesSynthesizes and secretes a number of hormones

Major Endocrine Organs: Pituitary Major Endocrine Organs: Pituitary (Hypophysis)(Hypophysis)

Figure 16.6

Pituitary-Hypothalamic Pituitary-Hypothalamic Relationships: Relationships: Posterior LobePosterior Lobe

The posterior lobe is a downgrowth of The posterior lobe is a downgrowth of hypothalamic neural tissuehypothalamic neural tissue

Has a neural connection with the Has a neural connection with the hypothalamus (hypothalamic-hypophyseal hypothalamus (hypothalamic-hypophyseal tract)tract)

Nuclei of the hypothalamus synthesize Nuclei of the hypothalamus synthesize oxytocin and antidiuretic hormone (ADH)oxytocin and antidiuretic hormone (ADH)

These hormones are transported to the These hormones are transported to the posterior pituitaryposterior pituitary

Pituitary-Hypothalamic Pituitary-Hypothalamic Relationships: Relationships: Anterior LobeAnterior Lobe

The anterior lobe of the pituitary is an The anterior lobe of the pituitary is an outpocketing of the oral mucosaoutpocketing of the oral mucosa

There is no direct neural contact with the There is no direct neural contact with the hypothalamushypothalamus

There is a vascular connection, the There is a vascular connection, the hypophyseal portal system, consisting of:hypophyseal portal system, consisting of: The primary capillary plexusThe primary capillary plexus The hypophyseal portal veinsThe hypophyseal portal veins The secondary capillary plexusThe secondary capillary plexus

Pituitary-Hypothalamic Pituitary-Hypothalamic Relationships: Relationships: Anterior LobeAnterior Lobe

Adenophypophyseal HormonesAdenophypophyseal Hormones

The six hormones of the adenohypophysis:The six hormones of the adenohypophysis: Abbreviated as GH, TSH, ACTH, FSH, LH, and Abbreviated as GH, TSH, ACTH, FSH, LH, and

PRLPRL Regulate the activity of other endocrine glandsRegulate the activity of other endocrine glands

In addition, pro-opiomelanocortin (POMC):In addition, pro-opiomelanocortin (POMC): Has been isolated from the pituitaryHas been isolated from the pituitary Is split into ACTH, opiates, and MSH Is split into ACTH, opiates, and MSH

Activity of the Activity of the AdenophypophysisAdenophypophysis

The hypothalamus sends a chemical stimulus The hypothalamus sends a chemical stimulus to the anterior pituitaryto the anterior pituitary Releasing hormones (RH) stimulate the synthesis Releasing hormones (RH) stimulate the synthesis

and release of hormonesand release of hormones Inhibiting hormones (IH) shut off the synthesis Inhibiting hormones (IH) shut off the synthesis

and release of hormonesand release of hormones Rate of secretion is controlled via negative Rate of secretion is controlled via negative

feedbackfeedback

Activity of the Activity of the AdenophypophysisAdenophypophysis

The tropic hormones that are released are:The tropic hormones that are released are: Thyroid-stimulating hormone (TSH) Thyroid-stimulating hormone (TSH) Adrenocorticotropic hormone (ACTH)Adrenocorticotropic hormone (ACTH) Follicle-stimulating hormone (FSH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH)Luteinizing hormone (LH)

Growth Hormone (GH)Growth Hormone (GH)

Produced by somatotropic cells of the anterior Produced by somatotropic cells of the anterior lobe that:lobe that: Stimulate most cells, but target bone and skeletal Stimulate most cells, but target bone and skeletal

musclemuscle Promote protein synthesis and encourage the use Promote protein synthesis and encourage the use

of fats for fuelof fats for fuel Most effects are mediated indirectly by Most effects are mediated indirectly by

somatomedinssomatomedins

Growth Hormone (GH)Growth Hormone (GH)

Antagonistic hypothalamic hormones regulate Antagonistic hypothalamic hormones regulate GHGH Growth hormone–releasing hormone (GHRH) Growth hormone–releasing hormone (GHRH)

stimulates GH releasestimulates GH release Growth hormone–inhibiting hormone (GHIH) Growth hormone–inhibiting hormone (GHIH)

inhibits GH releaseinhibits GH release

Metabolic Action of Growth Metabolic Action of Growth HormoneHormone

GH stimulates liver, skeletal muscle, bone, and GH stimulates liver, skeletal muscle, bone, and cartilage to produce insulin-like growth factorscartilage to produce insulin-like growth factors

Direct action promotes lipolysis and inhibits Direct action promotes lipolysis and inhibits glucose uptakeglucose uptake

Metabolic Action of Growth Metabolic Action of Growth Hormone (GH)Hormone (GH)

Figure 16.7

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

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

Triggered by hypothalamic peptide Triggered by hypothalamic peptide thyrotropin-releasing hormone (TRH)thyrotropin-releasing hormone (TRH)

Rising blood levels of thyroid hormones act on Rising blood levels of thyroid hormones act on the pituitary and hypothalamus to block the the pituitary and hypothalamus to block the release of TSHrelease of TSH

Adrenocorticotropic Hormone Adrenocorticotropic Hormone (Corticotropin)(Corticotropin)

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

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 trigger the hypoglycemia, and stressors can trigger the release of CRHrelease of CRH

GonadotropinsGonadotropins

Gonadotropins – follicle-stimulating hormone Gonadotropins – follicle-stimulating hormone (FSH) and luteinizing hormone (LH)(FSH) and luteinizing hormone (LH) Regulate the function of the ovaries and testesRegulate the function of the ovaries and testes FSH stimulates gamete (egg or sperm) productionFSH stimulates gamete (egg or sperm) production Absent from the blood in prepubertal boys and Absent from the blood in prepubertal boys and

girlsgirls Triggered by the hypothalamic gonadotropin-Triggered by the hypothalamic gonadotropin-

releasing hormone (GnRH) during and after releasing hormone (GnRH) during and after pubertypuberty

Functions of GonadotropinsFunctions of Gonadotropins

In femalesIn females LH works with FSH to cause maturation of the LH works with FSH to cause maturation of the

ovarian follicleovarian follicle LH works alone to trigger ovulation (expulsion of LH works alone to trigger ovulation (expulsion of

the egg from the follicle)the egg from the follicle) LH promotes synthesis and release of estrogens LH promotes synthesis and release of estrogens

and progesteroneand progesterone

Functions of GonadotropinsFunctions of Gonadotropins

In malesIn males LH stimulates interstitial cells of the testes to LH stimulates interstitial cells of the testes to

produce testosteroneproduce testosterone LH is also referred to as interstitial cell-stimulating LH is also referred to as interstitial cell-stimulating

hormone (ICSH)hormone (ICSH)

Prolactin (PRL)Prolactin (PRL)

In females, stimulates milk production by the In females, stimulates milk production by the breastsbreasts

Triggered by the hypothalamic prolactin-Triggered by the hypothalamic prolactin-releasing hormone (PRH)releasing hormone (PRH)

Inhibited by prolactin-inhibiting hormone (PIH)Inhibited by prolactin-inhibiting hormone (PIH) Blood levels rise toward the end of pregnancyBlood levels rise toward the end of pregnancy Suckling stimulates PRH release and encourages Suckling stimulates PRH release and encourages

continued milk productioncontinued milk production

The Posterior Pituitary and The Posterior Pituitary and Hypothalamic HormonesHypothalamic Hormones

Posterior pituitary – made of axons of Posterior pituitary – made of axons of hypothalamic neurons, stores antidiuretic hypothalamic neurons, stores antidiuretic hormone (ADH) and oxytocinhormone (ADH) and oxytocin

ADH and oxytocin are synthesized in the ADH and oxytocin are synthesized in the hypothalamushypothalamus

ADH influences water balanceADH influences water balance Oxytocin stimulates smooth muscle Oxytocin stimulates smooth muscle

contraction in breasts and uteruscontraction in breasts and uterus Both use PIP-calcium second-messenger Both use PIP-calcium second-messenger

mechanismmechanism