© 2013 Pearson Education, Inc. Endocrine System: Overview Acts with nervous system to coordinate...

Endocrine System: Overview

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

• Influences metabolic activities via hormones transported in blood

• Response slower but longer lasting than nervous system

• Endocrinology– Study of hormones and endocrine organs

• Controls and integrates– Reproduction– Growth and development– Maintenance of electrolyte, water, and

nutrient balance of blood– Regulation of cellular metabolism and energy

balance– Mobilization of body defenses

• Exocrine glands– Nonhormonal substances (sweat, saliva)– Have ducts to carry secretion to membrane

surface

• Endocrine glands– Produce hormones– Lack ducts

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

• Hypothalamus is Neuroendocrine organ• Some have exocrine and endocrine

functions– Pancreas, gonads, placenta

• Other tissues and organs that produce hormones– Adipose cells, thymus, and cells in walls of

small intestine, stomach, kidneys, and heart

Figure 16.1 Location of selected endocrine organs of the body.

Pineal glandHypothalamusPituitary gland

Thyroid glandParathyroid glands(on dorsal aspect of thyroid gland)Thymus

Adrenal glands

Pancreas

Gonads

• Testis (male)• Ovary (female)

Chemical Messengers

• Hormones: long-distance chemical signals; travel in blood or lymph

• Autocrines: chemicals that exert effects on same cells that secrete them

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

• Autocrines and paracrines are local chemical messengers; not considered part of endocrine system

Chemistry of Hormones

• Two main classes– Amino acid-based hormones

• Amino acid derivatives, peptides, and proteins

– Steroids• Synthesized from cholesterol• Gonadal and adrenocortical hormones

Mechanisms of Hormone Action

• Though hormones circulate systemically only cells with receptors for that hormone affected

• Target cells– Tissues with receptors for specific hormone

• Hormones alter target cell activity

• Hormone action on target cells may be to– Alter plasma membrane permeability and/or

membrane potential by opening or closing ion channels

– Stimulate synthesis of enzymes or other proteins

– Activate or deactivate enzymes– Induce secretory activity– Stimulate mitosis

• Hormones act at receptors in one of two ways, depending on their chemical nature and receptor location1. Water-soluble hormones (all amino acid–

based hormones except thyroid hormone)• Act on plasma membrane receptors• Act via G protein second messengers• Cannot enter cell

2. Lipid-soluble hormones (steroid and thyroid hormones)• Act on intracellular receptors that directly activate

genes• Can enter cell

Plasma Membrane Receptors and Second-messenger Systems

• cAMP signaling mechanism:1. Hormone (first messenger) binds to receptor

2. Receptor activates G protein

3. G protein activates adenylate cyclase

4. Adenylate cyclase converts ATP to cAMP (second messenger)

5. cAMP activates protein kinases that phosphorylate proteins

• cAMP signaling mechanism– Activated kinases phosphorylate various

proteins, activating some and inactivating others

– cAMP is rapidly degraded by enzyme phosphodiesterase

– Intracellular enzymatic cascades have huge amplification effect

Figure 16.2 Cyclic AMP second-messenger mechanism of water-soluble hormones.

Recall from Chapter 3 thatG protein signaling mechanismsare like a molecular relay race.

Hormone(1st messenger)

Receptor G protein Enzyme 2ndmessenger

Adenylate cyclase Extracellular fluid

G protein (Gs)

Receptor

Hormone (1st messenger) binds receptor.

Receptor activates G protein (Gs).

G protein activates adenylate cyclase.

Adenylate cyclase convertsATP to cAMP (2nd messenger).

Inactiveproteinkinase

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

Activeproteinkinase

cAMP activates protein kinases.

Cytoplasm

GTPGTP

Receptor G protein Enzyme 2ndmessenger Hormone (1st messenger)

binds receptor.1

Extracellular fluid

Receptor

Cytoplasm

Extracellular fluid

Hormone (1st messenger) binds receptor.1

G protein (Gs)

Receptor

Cytoplasm

G protein (Gs)

Receptor

Cytoplasm

GTPGTP

G protein (Gs)

Receptor

Cytoplasm

GTPGTP

G protein (Gs)

Receptor

Inactiveproteinkinase

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

Activeproteinkinase

cAMP activates protein kinases.

Cytoplasm

GTPGTP

• PIP2-calcium signaling mechanism

– Involves G protein and membrane-bound effector – phospholipase C

– Phospholipase C splits PIP2 into two second messengers – diacylglycerol (DAG) and inositol trisphosphate (IP3)

• DAG activates protein kinase; IP3 causes Ca2+ release

• Calcium ions act as second messenger

– Ca2+ alters enzyme activity and channels, or binds to regulatory protein calmodulin

– Calcium-bound calmodulin activates enzymes that amplify cellular response

Other Signaling Mechanisms

• Cyclic guanosine monophosphate (cGMP) is second messenger for some hormones

• Some work without second messengers– E.g., insulin receptor is tyrosine kinase

enzyme that autophosphorylates upon insulin binding docking for relay proteins that trigger cell responses

Intracellular Receptors and Direct Gene Activation

• Steroid hormones and thyroid hormone1. Diffuse into target cells and bind with

intracellular receptors2. Receptor-hormone complex enters nucleus;

binds to specific region of DNA3. Prompts DNA transcription to produce

mRNA4. mRNA directs protein synthesis5. Promote metabolic activities, or promote

synthesis of structural proteins or proteins for export from cell

Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones. Slide 1

The steroid hormone diffuses through the plasma membrane and binds an intracellular receptor.

The receptor-hormone complex enters the nucleus.

The receptor- hormone complex binds a specific DNA region.

Binding initiates transcription of the gene to mRNA.

The mRNA directs protein synthesis.

New protein

Nucleus

ReceptorBinding region

Receptor-hormonecomplex

Receptorprotein

Steroidhormone Plasma

membraneExtracellularfluid

Cytoplasm

Nucleus

Receptorprotein

Cytoplasm

Nucleus

Receptorprotein

Cytoplasm

Nucleus

Receptorprotein

Cytoplasm

Nucleus

Receptorprotein

Cytoplasm

Figure 16.3 Direct gene activation mechanism of lipid-soluble hormones.

The mRNA directs protein synthesis.

New protein

Nucleus

Receptorprotein

Cytoplasm

Target Cell Specificity

• Target cells must have specific receptors to which hormone binds, for example– ACTH receptors found only on certain cells of

adrenal cortex– Thyroxin receptors are found on nearly all

cells of body

Target Cell Activation

• Target cell activation depends on three factors– Blood levels of hormone– Relative number of receptors on or in target

cell– Affinity of binding between receptor and

hormone

Target Cell Activation

• Hormones influence number of their receptors– Up-regulation—target cells form more

receptors in response to low hormone levels– Down-regulation—target cells lose receptors

in response to high hormone levels

Control of Hormone Release

• Blood levels of hormones– Controlled by negative feedback systems– Vary only within narrow, desirable range

• Endocrine gland stimulated to synthesize and release hormones in response to– Humoral stimuli– Neural stimuli– Hormonal stimuli

Humoral Stimuli

• Changing blood levels of ions and nutrients directly stimulate secretion of hormones

• Example: Ca2+ in blood– Declining blood Ca2+ concentration stimulates

parathyroid glands to secrete PTH (parathyroid hormone)

– PTH causes Ca2+ concentrations to rise and stimulus is removed

Figure 16.4a Three types of endocrine gland stimuli. Slide 1

Humoral Stimulus

Hormone release caused by alteredlevels of certain critical ions ornutrients.

Stimulus: Low concentration of Ca2+ incapillary blood.

Parathyroidglands

Capillary (low Ca2+

in blood)

Thyroid gland(posterior view)

Response: Parathyroid glands secreteparathyroid hormone (PTH), whichincreases blood Ca2+.

Humoral Stimulus

Parathyroidglands

Capillary (low Ca2+

in blood)

Humoral Stimulus

Stimulus: Low concentration of Ca2+ incapillary blood.

Parathyroidglands

Capillary (low Ca2+

in blood)

Response: Parathyroid glands secreteparathyroid hormone (PTH), whichincreases blood Ca2+.

Neural Stimuli

• Nerve fibers stimulate hormone release– Sympathetic nervous system fibers stimulate

adrenal medulla to secrete catecholamines

Figure 16.4b Three types of endocrine gland stimuli. Slide 1

Neural Stimulus

Hormone release caused by neural input.

Stimulus: Action potentials in preganglionicsympathetic fibers to adrenal medulla.

CNS (spinal cord)

Preganglionicsympatheticfibers

Medulla ofadrenal gland

Capillary

Response: Adrenal medulla cells secreteepinephrine and norepinephrine.

Neural Stimulus

CNS (spinal cord)

Capillary

Neural Stimulus

Stimulus: Action potentials in preganglionicsympathetic fibers to adrenal medulla.

CNS (spinal cord)

Capillary

Response: Adrenal medulla cells secreteepinephrine and norepinephrine.

Hormonal Stimuli

• Hormones stimulate other endocrine organs to release their hormones – Hypothalamic hormones stimulate release of

most anterior pituitary hormones– Anterior pituitary hormones stimulate targets

to secrete still more hormones– Hypothalamic-pituitary-target endocrine organ

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

Figure 16.4c Three types of endocrine gland stimuli. Slide 1

Hormonal Stimulus

Hormone release caused by anotherhormone (a tropic hormone).

Stimulus: Hormones from hypothalamus.

Anteriorpituitarygland

Thyroidgland

Adrenalcortex

Gonad(Testis)

Hypothalamus

Response: Anterior pituitary gland secreteshormones that stimulate other endocrine glands to secrete hormones.

Hormonal Stimulus

Thyroidgland

Adrenalcortex

Gonad(Testis)

Hypothalamus

Hormonal Stimulus

Thyroidgland

Adrenalcortex

Gonad(Testis)

Hypothalamus

Hormonal Stimulus

Stimulus: Hormones from hypothalamus.

Thyroidgland

Adrenalcortex

Gonad(Testis)

Hypothalamus

Response: Anterior pituitary gland secreteshormones that stimulate other endocrine glands to secrete hormones.

Nervous System Modulation

• Nervous system modifies stimulation of endocrine glands and their negative feedback mechanisms – Example: under severe stress, hypothalamus

and sympathetic nervous system activated • body glucose levels rise

• Nervous system can override normal endocrine controls

Hormones in the Blood

• Hormones circulate in blood either free or bound– Steroids and thyroid hormone are attached to

plasma proteins– All others circulate without carriers

• Concentration of circulating hormone reflects – Rate of release– Speed of inactivation and removal from body

Hormones in the Blood

• Hormones removed from blood by– Degrading enzymes– Kidneys– Liver

• Half-life—time required for hormone's blood level to decrease by half

– Varies from fraction of minute to a week

Onset of Hormone Activity

• Some responses ~ immediate

• Some, especially steroid, hours to days

• Some must be activated in target cells

Duration of Hormone Activity

• Limited– Ranges from 10 seconds to several hours– Effects may disappear as blood levels drop– Some persist at low blood levels

Interaction of Hormones at Target Cells

• Multiple hormones may act on same target at same time– Permissiveness: one hormone cannot exert

its effects without another hormone being present

– Synergism: more than one hormone produces same effects on target cell amplification

– Antagonism: one or more hormones oppose(s) action of another hormone

The Pituitary Gland and Hypothalamus

• Pituitary gland (hypophysis) has two major lobes

– Posterior pituitary (lobe)• Neural tissue

– Anterior pituitary (lobe) (adenohypophysis)• Glandular tissue

Pituitary-hypothalamic Relationships

• Posterior pituitary (lobe)– Downgrowth of hypothalamic neural tissue– Neural connection to hypothalamus

(hypothalamic-hypophyseal tract)– Nuclei of hypothalamus synthesize

neurohormones oxytocin and antidiuretic hormone (ADH)

– Neurohormones are transported to and stored in posterior pituitary

Figure 16.5a The hypothalamus controls release of hormones from the pituitary gland in two different ways (1 of 2).

Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH).

Oxytocin and ADH are stored in axon terminals in the posterior pituitary.

When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood.

4OxytocinADH

Posterior lobeof pituitary

Opticchiasma

Infundibulum(connecting stalk)

Hypothalamic-hypophyseal

Axon terminals

Paraventricular nucleus

Hypothalamus

Supraopticnucleus

Inferiorhypophysealartery

Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary.

Opticchiasma

Axon terminals

Hypothalamus

Supraopticnucleus

Hypothalamic-hypophyseal

Opticchiasma

Axon terminals

Hypothalamus

Supraopticnucleus

Oxytocin and ADH are transported down the axons of the hypothalamic- hypophyseal tract to the posterior pituitary.Hypothalamic-

hypophysealtract

Opticchiasma

Axon terminals

Hypothalamus

Supraopticnucleus

hypophysealtract

When hypothalamic neurons fire, action potentials arriving at the axon terminals cause oxytocin or ADH to be released into the blood.

4OxytocinADH

Opticchiasma

Axon terminals

Hypothalamus

Supraopticnucleus

hypophysealtract

Pituitary-hypothalamic Relationships

• Anterior Lobe:– Originates as out-pocketing of oral mucosa– Vascular connection to hypothalamus

• Hypophyseal portal system– Primary capillary plexus– Hypophyseal portal veins– Secondary capillary plexus – Carries releasing and inhibiting hormones to anterior

pituitary to regulate hormone secretion

Figure 16.5b The hypothalamus controls release of hormones from the pituitary gland in two different ways (2 of 2).

Hypothalamic hormones travel through portal veins to the anterior pituitary where they stimulate or inhibit release of hormones made in the anterior pituitary.

In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation.

GH, TSH, ACTH,FSH, LH, PRL

Anterior lobeof pituitary

When appropriately stimulated, hypothalamic neurons secrete releasing or inhibiting hormones into the primary capillary plexus.

Hypophysealportal system

• Primary capillary plexus• Hypophyseal portal veins• Secondary capillary plexus

Superiorhypophyseal

artery

Hypothalamus Hypothalamicneurons synthesizeGHRH, GHIH, TRH,CRH, GnRH, PIH.

A portal system is two capillary plexuses (beds) connected by veins.

Superiorhypophyseal

artery

Superiorhypophyseal

artery

In response to releasing hormones, the anterior pituitary secretes hormones into the secondary capillary plexus. This in turn empties into the general circulation.

Superiorhypophyseal

artery

Posterior Pituitary and Hypothalamic Hormones

• Oxytocin and ADH– Each composed of nine amino acids– Almost identical – differ in two amino acids

Oxytocin

• Strong stimulant of uterine contraction

• Released during childbirth

• Hormonal trigger for milk ejection

• Acts as neurotransmitter in brain

ADH (Vasopressin)

• Inhibits or prevents urine formation

• Regulates water balance

• Targets kidney tubules reabsorb more water

• Release also triggered by pain, low blood pressure, and drugs

• Inhibited by alcohol, diuretics

• High concentrations vasoconstriction

• Diabetes insipidus– ADH deficiency due to hypothalamus or

posterior pituitary damage– Must keep well-hydrated

• Syndrome of inappropriate ADH secretion (SIADH)– Retention of fluid, headache, disorientation– Fluid restriction; blood sodium level

monitoring

Anterior Pituitary Hormones

• Growth hormone (GH)

• Thyroid-stimulating hormone (TSH) or thyrotropin

• Adrenocorticotropic hormone (ACTH)

• Follicle-stimulating hormone (FSH)

• Luteinizing hormone (LH)

• Prolactin (PRL)

Anterior Pituitary Hormones

• All are proteins

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

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

Growth Hormone (GH, or Somatotropin)

• Produced by somatotropic cells

• Direct actions on metabolism– Increases blood levels of fatty acids;

encourages use of fatty acids for fuel; protein synthesis

– Decreases rate of glucose uptake and metabolism – conserving glucose

Glycogen breakdown and glucose release to blood (anti-insulin effect)

Growth Hormone (GH, or Somatotropin)

• Indirect actions on growth

• Mediates growth via growth-promoting proteins – insulin-like growth factors (IGFs)

• IGFs stimulate– Uptake of nutrients DNA and proteins– Formation of collagen and deposition of bone

matrix

• Major targets—bone and skeletal muscle

Growth Hormone (GH)

• GH release chiefly regulated by hypothalamic hormones– Growth hormone–releasing hormone (GHRH)

• Stimulates release

– Growth hormone–inhibiting hormone (GHIH) (somatostatin)

• Inhibits release

• Ghrelin (hunger hormone) also stimulates release

Homeostatic Imbalances of Growth Hormone

• Hypersecretion– In children results in gigantism– In adults results in acromegaly

• Hyposecretion– In children results in pituitary dwarfism

Figure 16.6 Growth-promoting and metabolic actions of growth hormone (GH).

Hypothalamussecretes growthhormone–releasinghormone (GHRH), andGHIH (somatostatin)

Anteriorpituitary

Inhibits GHRH release

Stimulates GHIH release

Inhibits GH synthesisand release

Feedback

Indirect actions(growth-promoting)

Liver andother tissues

Insulin-like growthfactors (IGFs)

Produce

Effects

Skeletal ExtraskeletalFat

metabolismCarbohydratemetabolism

Direct actions(metabolic,anti-insulin)

Effects

Growth hormone (GH)

Increased cartilageformation and

skeletal growth

Increased proteinsynthesis, andcell growth and

proliferation

Increasedfat breakdown

and release

Increased bloodglucose and otheranti-insulin effects

Increases, stimulates

Initial stimulus

Reduces, inhibits

Physiological response

Result

Figure 16.7 Disorders of pituitary growth hormone.

Thyroid-stimulating Hormone (Thyrotropin)

• Produced by thyrotropic cells of anterior pituitary

• Stimulates normal development and secretory activity of thyroid

• Release triggered by thyrotropin-releasing hormone from hypothalamus

• Inhibited by rising blood levels of thyroid hormones that act on pituitary and hypothalamus

Hypothalamus

Anterior pituitary

Thyroid gland

Thyroidhormones

Target cellsStimulates

Figure 16.8 Regulation of thyroid hormone secretion.

Inhibits

Adrenocorticotropic Hormone (Corticotropin)

• Secreted by corticotropic cells of anterior pituitary

• Stimulates adrenal cortex to release corticosteroids

Adrenocorticotropic Hormone (Corticotropin)

• Regulation of ACTH release– Triggered by hypothalamic corticotropin-

releasing hormone (CRH) in daily rhythm– Internal and external factors such as fever,

hypoglycemia, and stressors can alter release of CRH

Gonadotropins

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

• Secreted by gonadotrophs of anterior pituitary

• FSH stimulates gamete (egg or sperm) production

• LH promotes production of gonadal hormones

• Absent from the blood in prepubertal boys and girls

Gonadotropins

• Regulation of gonadotropin release– Triggered by gonadotropin-releasing hormone

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

Prolactin (PRL)

• Secreted by prolactin cells of anterior pituitary

• Stimulates milk production

• Role in males not well understood

Prolactin (PRL)

• Regulation of PRL release– Primarily controlled by prolactin-inhibiting

hormone (PIH) (dopamine)

• Blood levels rise toward end of pregnancy

• Suckling stimulates PRL release and promotes continued milk production

• Hypersecretion causes inappropriate lactation, lack of menses, infertility in females, and impotence in males

© 2013 Pearson Education, Inc. Endocrine System: Overview Acts with nervous system to coordinate...

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