Chapter 18: The Endocrine System Muse lecture #14 7/1/10

Chapter 18: The Endocrine System

Muse lecture #147/1/10

Nervous and Endocrine Systems Act together to coordinate functions of all body

systems Nervous system

Nerve impulses/ Neurotransmitters Faster responses, briefer effects, acts on specific target

Endocrine system Hormone – mediator molecule released in 1 part of the

body but regulates activity of cells in other parts Slower responses, effects last longer, broader influence

Introduction to the Endocrine System The Endocrine System

Regulates long-term processes Growth Development Reproduction

Uses chemical messengers to relay information and instructions between cells

Endocrine Glands

2 kinds of glands Exocrine – ducted Endocrine – ductless

Secrete products into interstitial fluid, diffuse into blood

Endocrine glands include Pituitary, thyroid, parathyroid, adrenal and pineal glands Hypothalamus, thymus, pancreas, ovaries, testes, kidneys,

stomach, liver, small intestine, skin, heart, adipose tissue, and placenta not exclusively endocrine glands

Endocrine locations

Hormone Activity

Hormones affect only specific target tissues with specific receptors

Receptors constantly synthesized and broken down Down-regulation Up-regulation

Hormone types Circulating – circulate

in blood throughout body

Local hormones – act locally Paracrine – act on

neighboring cells Autocrine – act on

the same cell that secreted them

Chemical classes of hormones

Lipid-soluble – use transport proteins Steroid Thyroid Nitric oxide (NO)

Water-soluble – circulate in “free” form Amine Peptide/ protein Eicosanoid

Hormones

Figure 18–2 A Structural Classification of Hormones

Mechanisms of Hormone Action Response depends on both hormone and target cell Lipid-soluble hormones bind to receptors inside target

cells Water-soluble hormones bind to receptors on the

plasma membrane Activates second messenger system Amplification of original small signal

Responsiveness of target cell depends on Hormone’s concentration Abundance of target cell receptors Influence exerted by other hormones

Permissive, synergistic and antagonistic effects

Lipid-soluble and Water-soluble Hormones

Mechanisms of Hormone Action Hormones and Plasma Membrane Receptors

Catecholamines and peptide hormones Are not lipid soluble Unable to penetrate plasma membrane Bind to receptor proteins at outer surface of plasma

membrane (extracellular receptors)

1 Lipid-solublehormonediffuses into cell

Blood capillary

Target cell

Transportprotein

Free hormone


Blood capillary

Activatedreceptor-hormonecomplex altersgene expression

NucleusReceptor

mRNA

DNA

Cytosol

Target cell

Transportprotein

Free hormone

2


Blood capillary


NucleusReceptor

mRNANewly formedmRNA directssynthesis ofspecific proteinson ribosomes

DNA

Cytosol

Target cell

Transportprotein

Free hormone

Ribosome

2

3


Blood capillary


NucleusReceptor

mRNANewly formedmRNA directssynthesis ofspecific proteinson ribosomes

DNA

Cytosol

Target cell

New proteins altercell's activity

Transportprotein

Free hormone

Ribosome

Newprotein

2

3

4

Copyright 2009, John Wiley & Sons, Inc.

Mechanisms of Hormone Action Important Second Messengers

Cyclic-AMP (cAMP) Derivative of ATP

Cyclic-GMP (cGMP) Derivative of GTP

Calcium ions

Mechanisms of Hormone Action Hormones and Plasma Membrane Receptors

G Protein

Enzyme complex coupled to membrane receptor

Involved in link between first messenger and second

messenger

Binds GTP

Activated when hormone binds to receptor at membrane

surface and changes concentration of second messenger

cyclic-AMP (cAMP) within cell:

increased cAMP level accelerates metabolic activity within cell

Water-solublehormone

Receptor

G protein

Blood capillary

Binding of hormone (first messenger)to its receptor activates G protein,which activates adenylate cyclase

Adenylate cyclase

Target cell

1


Receptor

G protein

cAMP

Second messenger

Activated adenylatecyclase convertsATP to cAMP

Blood capillary


Adenylate cyclase

Target cell

ATP

1

2


Receptor

cAMP serves as asecond messengerto activate proteinkinases

G protein

Protein kinases

cAMP

Second messenger


Blood capillary


Adenylate cyclase

Target cell

ATP

1

2

3 Activatedproteinkinases


Receptor


G protein

Protein kinases

cAMP

Activatedproteinkinases

Second messenger


Activated proteinkinasesphosphorylatecellular proteins

Blood capillary


Adenylate cyclase

Target cell

ATP

1

2

4

3

Protein— P

ADP

Protein

ATP


Receptor


G protein

Protein kinases

cAMP


Protein—

Second messenger



Millions of phosphorylatedproteins cause reactions thatproduce physiological responses

Blood capillary


Adenylate cyclase

Target cell

P

ADP

Protein

ATP

ATP

1

2

4

3

5


Receptor


G protein

Protein kinases

cAMP


Protein—

Second messenger

Phosphodiesteraseinactivates cAMP



Millions of phosphorylatedproteins cause reactions thatproduce physiological responses

Blood capillary


Adenylate cyclase

Target cell

P

ADP

Protein

ATP

ATP

1

2

6

4

3

5

Control of Hormone Secretion Regulated by

Signals from nervous system

Chemical changes in the blood

Other hormones Most hormonal

regulation by negative feedback Few examples of positive

feedback

Hypothalamus and Pituitary Gland Hypothalamus is a major link between

nervous and endocrine system Pituitary attached to hypothalamus by

infundibulum Anterior pituitary or adenohypophysis Posterior pituitary or neurohypophysis

Hypothalamus and Pituitary Gland

Pituitary Gland

Figure 18–9 Pituitary Hormones and Their Targets.

Anterior pituitary

Release of hormones stimulated by releasing and inhibiting hormones from the hypothalamus

Also regulated by negative feedback Hypothalamic hormones made by

neurosecretory cells transported by hypophyseal portal system

Anterior pituitary hormones that act on other endocrine systems called tropic hormones

Hormones of the Anterior Pituitary Human growth hormone (hGH) or somatostatin

Stimulates secretion of insulin-like growth factors (IGFs) that promote growth, protein synthesis

Thyroid-stimulating hormone (TSH) or thyrotropin Stimulates synthesis and secretion of thyroid hormones by

thyroid Follicle-stimulating hormone (FSH)

Ovaries initiates development of oocytes, testes stimulates testosterone production

Luteinizing hormone (LH) Ovaries stimulates ovulation, testes stimulates testosterone

production

Hormones of the Anterior Pituitary Prolactin (PRL)

Promotes milk secretion by mammary glands Adrenocorticotropic hormone (ACTH) or

corticotropin Stimulates glucocorticoid secretion by adrenal

cortex Melanocyte-stimulating Hormone (MSH)

Unknown role in humans

Pituitary Gland

Figure 18–8a Feedback Control of Endocrine Secretion

Negative Feedback Regulation

Effects of hGH and IGFs

Low blood glucose(hypoglycemia)stimulates release of

GHRH

1 Low blood glucose(hypoglycemia)stimulates release of

hGH

GHRH stimulatessecretionof hGH bysomatotrophs

GHRH

1

2


hGH


GHRH

hGH and IGFs speedup breakdown of liverglycogen into glucose,which enters the bloodmore rapidly

1

3

2


hGH


GHRH


Blood glucose levelrises to normal(about 90 mg/100 mL)

1

3

4

2


hGH


GHRH



If blood glucosecontinues to increase,hyperglycemia inhibitsrelease of GHRH

1

3

4

5

2

Anteriorpituitary


High blood glucose(hyperglycemia)stimulates release of

hGH


GHIHGHRH




1 6

3

4

5

2

Anteriorpituitary

GHIH inhibitssecretion ofhGH bysomatotrophs



hGH


GHIHGHRH




1 6

7

3

4

5

2 GHIH inhibitssecretion ofhGH bysomatotrophs



Anteriorpituitary

hGH


GHIHGHRH

A low level of hGH andIGFs decreases the rateof glycogen breakdownin the liver and glucoseenters the blood moreslowly




1 6

7

83

4

5




Anteriorpituitary

hGH


GHIHGHRH


Blood glucose levelfalls to normal(about 90 mg/100 mL)




1 6

7

8

9

3

4

5




Anteriorpituitary

hGH


GHIHGHRH


Blood glucose levelfalls to normal(about 90 mg/100 mL)




If blood glucosecontinues to decrease,hypoglycemia inhibitsrelease of GHIH

1 6

7

8

9

10

3

4

5

2

Posterior pituitary

Does not synthesize hormones Stores and releases hormones made by the

hypothalamus Transported along hypothalamohypophyseal tract

Oxytocin (OT) Antidiuretic hormone (ADH) or vasopressin

Hypothalamohypophyseal tract

Oxytocin (OT)

During and after delivery of baby affects uterus and breasts

Enhances smooth muscle contraction in wall of uterus

Stimulates milk ejection from mammary glands

Antidiuretic Hormone (ADH)

Decreases urine production by causing the kindeys to return more water to the blood

Also decreases water lost through sweating and constriction of arterioles which increases blood pressure (vasopressin)

Osmoreceptors

High blood osmoticpressure stimulateshypothalamicosmoreceptors

1

Osmoreceptors


Osmoreceptorsactivate theneurosecretory cellsthat synthesize andrelease ADH

Hypothalamus

1

2Osmoreceptors


Nerve impulsesliberate ADH fromaxon terminals inthe posteriorpituitary intothe bloodstream


Hypothalamus

ADH

1

2

3

Osmoreceptors




Hypothalamus

Sudoriferous(sweat) glandsdecrease waterloss by perspirationfrom the skin

Arterioles constrict,which increasesblood pressure

Kidneys retainmore water,which decreasesurine output

ADH

Target tissues

1

2

3

4

Osmoreceptors


Low blood osmoticpressure inhibitshypothalamicosmoreceptors



Hypothalamus




ADH

Target tissues

1

2

3

4

5

Osmoreceptors


Low blood osmoticpressure inhibitshypothalamicosmoreceptors



Hypothalamus

Inhibition of osmo-receptors reduces orstops ADH secretion




ADH

Target tissues

1

2

3

4

5

6

Thyroid Gland

Located inferior to larynx 2 lobes connected by isthmus Thyroid follicles produce thyroid hormones

Thyroxine or tetraiodothyronine (T4)

Triiodothyronine (T3) Both increase BMR, stimulate protein synthesis, increase use

of glucose and fatty acids for ATP production

Parafollicular cells or C cells produce calcitonin Lowers blood Ca2+ by inhibiting bone resorption

Thyroid Gland

Control of thyroid hormone secretion

Thyrotropin-releasing hormone (TRH) from hypothalamus

Thyroid-stimulating hormone (TSH) from anterior pituitary

Situations that increase ATP demand also increase secretion of thyroid hormones

Hypothalamus

Anterior pituitary

Thyroid gland

Thyroidhormones

TSH

TRH

Target cellsStimulates

Inhibits

Low blood levels of T3

and T3 or low metabolicrate stimulate release of

HypothalamusTRH

Actions of Thyroid Hormones:

Increase basal metabolic rate

Stimulate synthesis of Na+/K+ ATPase

Increase body temperature (calorigenic effect)

Stimulate protein synthesis

Increase the use of glucose and fatty acids for ATP production

Stimulate lipolysis

Enhance some actions of catecholamines

Regulate development and growth of nervous tissue and bones

1

Anteriorpituitary

TRH, carriedby hypophysealportal veins toanterior pituitary,stimulatesrelease of TSHby thyrotrophs



Hypothalamus

TSH

TRH







Stimulate lipolysis



1

2

Anteriorpituitary


TSH released intoblood stimulatesthyroid follicular cells

Thyroidfollicle



Hypothalamus

Anteriorpituitary

TSH

TRH







Stimulate lipolysis



1

2

3

T3 and T4

released intoblood byfollicular cells



Thyroidfollicle



Hypothalamus

Anteriorpituitary

TSH

TRH







Stimulate lipolysis



1

2

3

4 T3 and T4

released intoblood byfollicular cells

ElevatedT3inhibitsrelease ofTRH andTSH(negativefeedback)



Thyroidfollicle



Hypothalamus

Anteriorpituitary

TSH

TRH







Stimulate lipolysis



1

2

3

5

4

Parathyroid Glands

Embedded in lobes of thyroid gland Usually 4 Parathyroid hormone (PTH) or parathormone

Major regulator of calcium, magnesium, and phosphate ions in the blood

Increases number and activity of osteoclasts Elevates bone resorption

Blood calcium level directly controls secretion of both calcitonin and PTH via negative feedback

Parathyroid Glands

Roles of Calcitonin, Parathyroid hormone, Calcitrol in Calcium Homeostasis

1 High level of Ca2+ in bloodstimulates thyroid glandparafollicular cells to release more CT.


CALCITONIN inhibitsosteoclasts, thus decreasingblood Ca2+ level.

2


Low level of Ca2+ in bloodstimulates parathyroid gland chief cells to release more PTH.


3

2




PARATHYROID HORMONE (PTH)promotes release of Ca2+ frombone extracellular matrix intoblood and slows loss of Ca2+ in urine, thus increasing bloodCa2+ level.

3

4 2

1

PTH also stimulatesthe kidneys to releaseCALCITRIOL.

High level of Ca2+ in bloodstimulates thyroid glandparafollicular cells to release more CT.




3

4 25

1

CALCITRIOL stimulatesincreased absorption ofCa2+ from foods, whichincreases blood Ca2+ level.

PTH also stimulatesthe kidneys to releaseCALCITRIOL.

High level of Ca2+ in bloodstimulates thyroid glandparafollicular cells to release more CT.




3

4 25

6

Adrenal Glands

2 structurally and functionally distinct regions Adrenal cortex

Mineralocorticoids affect mineral homeostasis Glucocorticoids affect glucose homeostasis

cortisol Androgens have masculinzing effects

Dehydroepiandrosterone (DHEA) only important in females Adrenal medulla

Modified sympathetic ganglion of autonomic nervous system

Intensifies sympathetic responses Epinephrine and norepinephrine

Adrenal Glands

Pancreatic Islets

Both exocrine and endocrine gland Roughly 99% of cells produce digestive enzymes Pancreatic islets or islets of Langerhans

Alpha or A cells secrete glucagon – raises blood sugar Beta or B cells secrete insulin – lowers blood sugar Delta or D cells secrete somatostatin – inhibits both insulin

and glucagon F cells secrete pancreatic polypeptide – inhibits

somatostatin, gallbladder contraction, and secretion of pancreatic digestive enzymes

Pancreas

Pancreas

Insulin Is a peptide hormone released by beta cells Affects target cells

Accelerates glucose uptake Accelerates glucose utilization and enhances ATP production Stimulates glycogen formation Stimulates amino acid absorption and protein synthesis Stimulates triglyceride formation in adipose tissue

Pancreas

Negative Feedback Regulation of Glucagon and Insulin

Low blood glucose(hypoglycemia)stimulates alphacells to secrete

1

GLUCAGON

Glucagon acts onhepatocytes(liver cells) to:

• convert glycogen into glucose (glycogenolysis)• form glucose from lactic acid and certain amino acids (gluconeogenesis)


GLUCAGON

1

2 Glucagon acts onhepatocytes(liver cells) to:


Glucose releasedby hepatocytesraises blood glucoselevel to normal


GLUCAGON

1

2

3




If blood glucosecontinues to rise,hyperglycemia inhibitsrelease of glucagon


GLUCAGON

1

2

3

4






High blood glucose(hyperglycemia)stimulates beta cellsto secrete

GLUCAGON

1 5

2

3

4

INSULIN

Insulin acts on variousbody cells to:

• accelerate facilitated diffusion of glucose into cells• speed conversion of glucose into glycogen (glycogenesis)• increase uptake of amino acids and increase protein synthesis• speed synthesis of fatty acids (lipogenesis)• slow glycogenolysis• slow gluconeogenesis







INSULINGLUCAGON

1 5

2

3

4

6 Insulin acts on variousbody cells to:


Blood glucose level falls







INSULINGLUCAGON

1 5

2

3

4

6

7

Insulin acts on variousbody cells to:


If blood glucose continuesto fall, hypoglycemiainhibits release ofinsulin

Blood glucose level falls







INSULINGLUCAGON

1 5

2

3

4

6

7

8

Liver

Liver

Tissue cells

Stimulates glucose uptake by cells

Stimulatesglycogenformation

Pancreas

Pancreas

Insulin

Bloodglucosefalls tonormalrange.

Stimulatesglycogenbreakdown

Bloodglucoserises tonormalrange.

Glucagon

Stimulus

Bloodglucose level

Stimulus

Bloodglucose level

GlycogenGlucose

GlycogenGlucose

Ovaries and Testes

Gonads – produce gametes and hormones Ovaries produce 2 estrogens (estradiol and estrone)

and progesterone With FSH and LH regulate menstrual cycle, maintain

pregnancy, prepare mammary glands for lactation, maintain female secondary sex characteristics

Inhibin inhibits FSH Relaxin produced during pregnancy

Testes produce testosterone – regulates sperm production and maintains male secondary sex characteristics Inhibin inhibits FSH

Pineal Gland

Attached to roof of 3rd ventricle of brain at midline

Masses of neuroglia and pinealocytes Melatonin – amine hormone derived from

serotonin Appears to contribute to setting biological

clock More melatonin liberated during darkness

than light

Pineal Gland

Functions of Melatonin Inhibiting reproductive functions Protecting against damage by free radicals Setting circadian rhythms

Thymus and Other Endocrine Tissues Thymus

Located behind sternum between the lungs Produces thymosin, thymic humoral factor

(THF), thymic factor (TF), and thymopoietin All involved in T cell maturation

The Stress Response

Eustress in helpful stress / Distress is harmful Body’s homeostatic mechanisms attempt to

counteract stress Stressful conditions can result in stress response or

general adaptation syndrome (GAS) 3 stages – initial flight-or-fight, slower resistance reaction,

eventually exhaustion Prolonged exposure to cortisol can result in wasting of

muscles, suppression of immune system, ulceration of GI tract, and failure of pancreatic beta cells

Hormone Interactions General Adaptation Syndrome (GAS)

Also called stress response How body responds to stress-causing factors Is divided into three phases:

– Alarm phase – Resistance phase– Exhaustion phase

Figure 18–18

Stress Response

Hormone Interactions

Figure 18–18 The General Adaptation Syndrome.

Hormone Interactions

Figure 18–18 The General Adaptation Syndrome.


Mechanisms of Hormone Action

Figure 18–4b Effects of Intracellular Hormone Binding.


Mechanisms of Hormone Action

Figure 18–3 G Proteins and Hormone Activity.

Documents

Chapter 18: The Endocrine System Muse lecture #14 7/1/10