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Chapter 18

The Endocrine System


An Introduction to the Endocrine System

Endocrine system

– Endocrine cells and tissues produce about 30 different

hormones (chemical messengers)

– Controls and coordinates body processes

2


18-1 Intercellular Communication

Mechanisms of intercellular communication

– Direct communication

• Exchange of ions and molecules between adjacent

cells across gap junctions

• Occurs between two cells of the same type

• Highly specialized and relatively rare

– Paracrine communication

• Chemical signals transfer information from cell to

cell within a single tissue

3



Mechanisms of intercellular communication

– Autocrine communication

• Messages affect the same cells that secrete them

• Chemicals involved are autocrines

• Example: prostaglandins secreted by smooth

muscle cells cause the same cells to contract

– Endocrine communication

• Endocrine cells release chemicals (hormones) that

are transported in bloodstream

• Alters metabolic activities of many organs

4



Target cells

– Have receptors needed to bind and “read” hormonal

messages

Hormones

– Change types, quantities, or activities of enzymes and

structural proteins in target cells

– Can alter metabolic activities of multiple tissues and

organs at the same time

– Affect long-term processes like growth and

development

5



Synaptic communication

– Neurons release neurotransmitters at a synapse

– Leads to action potentials that are propagated along

axons

– Allows for high-speed “messages” to reach specific

destinations

– Ideal for crisis management

6


18-2 Hormones

Both endocrine and nervous systems

– Rely on release of chemicals that bind to specific

receptors on target cells

– Share many chemical messengers (e.g.,

norepinephrine and epinephrine)

– Are regulated mainly by negative feedback

– Function to preserve homeostasis by coordinating and

regulating activities

7


18-2 Hormones

Endocrine system

– Includes all endocrine cells and tissues that produce

hormones or paracrines

– Endocrine cells release secretions into extracellular

fluid

• Unlike exocrine cells

– Endocrine organs are scattered throughout body

8

Figure 18–1 Organs and Tissues of the Endocrine System (Part 1 of 2).

Hypothalamus

Production of ADH, OXT,

and regulatory hormones

Pituitary Gland

Anterior lobe

ACTH, TSH, GH, PRL,

FSH, LH, and MSH

Posterior lobe

Release of oxytocin (OXT)

and antidiuretic hormone (ADH)

Pineal Gland

Melatonin

Parathyroid Glands

(located on the posterior surfacesof the thyroid gland)

Parathyroid hormone (PTH)

9

Figure 18–1 Organs and Tissues of the Endocrine System (Part 2 of 2).

Organs with Secondary

Endocrine Functions

Heart

• Atrial natriuretic peptide (ANP)

• Brain natriuretic peptide (BNP)

Thymus (undergoes atrophy

during adulthood)

• Thymosins

Adipose Tissue

• Leptin

Digestive Tract

Secretes numerous hormones

involved in the coordination of

system functions, glucose

metabolism, and appetite

Kidneys

• Erythropoietin (EPO)

• Calcitriol

Gonads

Testes (male)

• Androgens (especially testosterone)• Inhibin

Ovary

Ovaries (female)

• Estrogens

• Progesterone

• Inhibin

See

Chapter

25

See

Chapter

21

See

Chapter

22

Thyroid Gland

Thyroxine (T4)

Triiodothyronine (T3)

Calcitonin (CT)

Adrenal Glands

Medulla

Epinephrine (E)

Norepinephrine (NE)

Cortex

Cortisol, corticosterone,

cortisone, aldosterone,

androgens

Pancreas

(Pancreatic Islets)

Insulin, glucagon

KEY TO PITUITARY HORMONES

ACTH

TSH

GH

PRL

FSH

LH

MSH

Adrenocorticotropic hormone

Thyroid-stimulating hormone

Growth hormone

Prolactin

Follicle-stimulating hormone

Luteinizing hormone

Melanocyte-stimulating hormone

Testis

See

Chapters

19 and 26

See

Chapters

28 and 29

10


18-2 Hormones

Classes of hormones

– Amino acid derivatives

– Peptide hormones

– Lipid derivatives

11


18-2 Hormones

Amino acid derivatives (biogenic amines)

– Small molecules structurally related to amino acids

– Derivatives of tyrosine

• Thyroid hormones

• Catecholamines (epinephrine, norepinephrine, and

dopamine)

– Derivatives of tryptophan

• Serotonin and melatonin

12


18-2 Hormones

Peptide hormones

– Chains of amino acids

– Most are synthesized as prohormones

• Inactive molecules converted to active hormones

before or after they are secreted

– Glycoproteins

• Proteins more than 200 amino acids long that have

carbohydrate side chains (e.g., TSH, LH, FSH)

– Short polypeptides/small proteins

13


18-2 Hormones

Peptide hormones

– Short-chain polypeptides

• ADH and OXT are each 9 amino acids long

– Small proteins

• Insulin (51 amino acids)

• Growth hormone (191 amino acids)

• Prolactin (198 amino acids)

– Includes all hormones secreted by hypothalamus,

heart, thymus, digestive tract, pancreas, posterior lobe

of the pituitary gland, etc.

14


18-2 Hormones

Lipid derivatives

– Eicosanoids—derived from arachidonic acid, a 20-

carbon fatty acid

• Paracrines that coordinate cellular activities and

affect enzymatic processes (such as blood clotting)

• Some eicosanoids (such as leukotrienes) have

secondary roles as hormones

• Prostaglandins coordinate local cellular activities

– Converted to thromboxanes and prostacyclins in

some tissues

15


18-2 Hormones

Lipid derivatives

– Steroid hormones—derived from cholesterol

• Include

– Androgens from testes in males

– Estrogens and progesterone from ovaries in

females

– Corticosteroids from adrenal cortex

– Calcitriol from kidneys

• Bound to specific transport proteins in the plasma

– Remain in circulation longer than peptide

hormones

16


18-2 Hormones

Transport and inactivation of hormones

– Hormones may circulate freely or travel bound to

special carrier proteins

– Free hormones remain functional for less than an hour

and are inactivated when they

• Diffuse out of bloodstream and bind to receptors on

target cells,

• Are absorbed and broken down by liver or kidneys,

or

• Are broken down by enzymes in blood or interstitial

fluids

17


18-2 Hormones

Transport and inactivation of hormones

– Thyroid and steroid hormones

• Remain functional much longer

• More than 99 percent become attached to special

transport proteins in blood

• Equilibrium state exists between free and bound

forms

• Bloodstream contains a substantial reserve of

bound hormones

18


18-2 Hormones

Mechanisms of hormone action

– Binding of a hormone may

• Alter genetic activity

• Alter rate of protein synthesis

• Change membrane permeability

19


18-2 Hormones

Hormone receptor

– A protein molecule to which a particular molecule binds

strongly

– Different tissues have different combinations of

receptors

– Presence or absence of a specific receptor determines

hormonal sensitivity of a cell

20


18-2 Hormones

Down-regulation

– Presence of a hormone triggers a decrease in the

number of hormone receptors

– When levels of a particular hormone are high, cells

become less sensitive to it

Up-regulation

– Absence of a hormone triggers an increase in the

number of hormone receptors

– When levels of a particular hormone are low, cells

become more sensitive to it

21


18-2 Hormones

Catecholamines and peptide hormones

– Not lipid soluble

– Unable to penetrate plasma membrane

– Bind to receptor proteins on outer surface of plasma

membrane (extracellular receptors)

Steroid and thyroid hormones

– Lipid soluble

– Diffuse across plasma membrane and bind to

receptors inside cell (intracellular receptors)

22


18-2 Hormones

Hormones and extracellular receptors

– First messenger

• Hormone that binds to extracellular receptor

• Promotes release of second messenger in cell

– Second messenger

• Intermediary molecule that appears due to

hormone–receptor interaction

• May act as enzyme activator, inhibitor, or cofactor

• Results in change in rates of metabolic reactions

• Example: cAMP, cGMP, Ca2+

23


18-2 Hormones

Process of amplification

– When a small number of hormone molecules binds to

extracellular receptors,

• Thousands of second messengers may appear

– Magnifies effect of hormone on target cell

24


18-2 Hormones

G protein

– Enzyme complex coupled to membrane receptor

– Protein binds GTP

– Involved in link between first messenger and second

messenger

25


18-2 Hormones

G proteins and cAMP

– Steps involved in increasing cAMP level, which

accelerates metabolic activity of cell

1. Activated G protein activates adenylate cyclase

2. Adenylate cyclase converts ATP to cyclic AMP

3. Cyclic AMP functions as a second messenger

4. Generally, cyclic AMP activates kinases that

phosphorylate proteins

– Increase in cAMP level is usually short-lived

• Phosphodiesterase (PDE) converts cAMP to AMP

26

Figure 18–3a G Proteins and Second Messengers.

The first messenger

(a peptide hormone,

catecholamine, or

eicosanoid) binds to a

membrane receptor and

activates a G protein.

Hormone

A G protein is an

enzyme complex

coupled to a

membrane receptor

that serves as a link

between the first and

second messenger.

Hormone

Proteinreceptor

G protein(inactive)

Proteinreceptor

G proteinactivated

a Effects on cAMP Level

Many G proteins, once activated, exert their effects by changing the

concentration of cyclic AMP, which acts as the second messenger within the

cell.

HormoneHormone

Protein

receptor

G proteinactivated

Acts as

second

messenger

adenylate

cyclase

Proteinreceptor

Increased

production

of cAMP

ATP

G proteinactivated

PDE

Enhanced

breakdown

of cAMP

AMPcAMP

kinase

Opens ion

channels

Activates

enzymes

Reduced

enzyme

activity

If levels of cAMP increase,

enzymes may be activated

or ion channels may be

opened, accelerating the

metabolic activity of the cell.

In some instances, G protein

activation results in

decreased levels of cAMP in

the cytoplasm. This decrease

has an inhibitory effect on

the cell.

First Messenger Examples

• Epinephrine and

norepinephrine


• Epinephrine and

norepinephrine

• Calcitonin

• Parathyroid hormone

• ADH, ACTH, FSH, LH, TSH

cAMP

a

27


18-2 Hormones

G proteins and calcium ions

1. G protein activates phospholipase C (PLC)

2. Triggers receptor cascade beginning with production

of diacylglycerol (DAG) and inositol triphosphate

(IP3) from phospholipids

3. IP3 diffuses into cytoplasm and triggers release of

Ca2+ from intracellular reserves

4. Calcium ion channels open due to activation of

protein kinase C (PKC), and Ca2+ enters cell

5. Ca2+ binds to calmodulin, activating enzymes

28

Figure 18–3b G Proteins and Second Messengers.

The first messenger

(a peptide hormone,

catecholamine, or

eicosanoid) binds to a

membrane receptor and

activates a G protein.

Hormone

A G protein is an

enzyme complex

coupled to a

membrane receptor

that serves as a link

between the first and

second messenger.

Hormone

Proteinreceptor

G protein(inactive)

Proteinreceptor

G proteinactivated

Effects on Ca2+

Level

Hormone

Proteinreceptor

G proteinactivated

PKC

Calmodulin

Activates

enzymes


• Epinephrine and norepinephrine

• Oxytocin

• Regulatory hormones of hypothalamus

• Several eicosanoids

b

29


18-2 Hormones

Hormones and intracellular receptors

– Steroid hormones can alter rate of DNA transcription in

nucleus

– Alterations in synthesis of enzymes or structural

proteins

• Directly affect activity and structure of target cell

– Thyroid hormones bind to receptors within nucleus and

on mitochondria

• Activate genes or change rate of transcription

• Increase rates of ATP production

30

Figure 18–4a Effects of Intracellular Hormone Binding.

Steroid hormones diffuse through the plasma membrane

and bind to receptors in the cytoplasm or nucleus.

The complex then binds to DNA in the nucleus,

activating specific genes.

1

Diffusion through

membrane lipids

Target cell response

CYTOPLASM

Alteration of cellular

structure or activity

6

Receptor

Binding of hormone

to cytoplasmic or

nuclear receptors

Translation and

protein synthesis

2

5

Transcription and

mRNA production

Receptor

Nuclear

pore

Nuclear

envelope

3

4

Gene activation

Binding of

hormone–receptor

complex to DNA

a

31

Figure 18–4b Effects of Intracellular Hormone Binding.

Thyroid hormones enter the cytoplasm and bind to

receptors in the nucleus to activate specific genes.

They also bind to receptors on mitochondria and

accelerate ATP production.

1

Transport across

plasma membrane

Target cell response

Increased

ATP

production

Receptor6

Translation and

protein synthesis

2

Binding of receptors

at mitochondria and

nucleus

5

Transcription and

mRNA production

Receptor

4Gene activation

3

Binding of

hormone–receptor

complex to DNA

Alteration of cellular

structure or activity

b

32


18-2 Hormones

Hormone secretion

– Mainly controlled by negative feedback

• Stimulus triggers production of hormone that

reduces intensity of the stimulus

– Can be triggered by

• Humoral stimuli (change in extracellular fluid),

• Hormonal stimuli (arrival or removal of hormone), or

• Neural stimuli (neurotransmitters)

33


18-2 Hormones

Control of hormone secretion

– May involve only one hormone

– Humoral stimuli

• Control hormone secretion by heart, pancreas,

parathyroid gland, and digestive tract

– Hormonal stimuli

• May involve one or more intermediary steps

• Two or more hormones involved

– Neural stimuli

• Hypothalamus provides highest level of control

34


18-3 The Pituitary Gland

Pituitary gland (hypophysis)

– Lies within sella turcica

• Sellar diaphragm isolates pituitary gland from

cranial cavity

– Hangs inferior to hypothalamus

• Connected by infundibulum

– Releases nine important peptide hormones

• Bind to extracellular receptors

• Use cAMP as second messenger

35

Figure 18–5a The Orientation and Anatomy of the Pituitary Gland.

Third

ventricle

Hypothalamus

Optic chiasm

Infundibulum

Sellar diaphragm

Anterior Pituitary Lobe

Pars tuberalis

Pars distalis

Pars intermedia

Mammillary

body

Posterior

pituitary

lobe

Sphenoid

(sella turcica)

Relationship of the pituitary

gland to the hypothalamus

a

36

Anterior Pituitary Lobe

Pars

distalis

Pars

intermedia

Posterior

pituitary

lobe

Secretes other

pituitary

hormones

Pituitary gland

Secretes

MSH

Releases

ADH and

OXT

LM × 77

Histology of the pituitary gland showing the

anterior and posterior lobes

b

Figure 18–5b The Orientation and Anatomy of the Pituitary Gland.

37



The hypothalamus

– Regulates functions of the pituitary gland

– Synthesizes ADH and OXT and transports them to

posterior pituitary gland for release

– Secretes regulatory hormones that control secretory

activity of anterior pituitary gland

– Contains autonomic centers that exert direct control

over adrenal medulla

38

Figure 18–6 Three Mechanisms of Hypothalamic Control over Endocrine Function.

Production of

antidiuretic

hormone (ADH)

and oxytocin (OXT)

Secretion of regulatory

hormones to control

activity of the anterior

lobe of the pituitary gland

Control of

sympathetic

output to adrenal

medulla

HYPOTHALAMUS Preganglionic

motor fibers

Adrenal Gland

InfundibulumAdrenal cortex

Adrenal medulla

Anterior lobe

of pituitary gland

Posterior lobe

of pituitary gland

Hormones secreted by

the anterior lobe control

other endocrine organs

Release of antidiuretic

hormone (ADH) and oxytocin

(OXT) from posterior lobe

Secretion of epinephrine (E)

and norepinephrine (NE)

from adrenal medulla

39



Anterior lobe of pituitary gland

– Also called adenohypophysis

• Hormones “turn on” endocrine glands or support

functions of other organs

• Has three regions

– Pars distalis

– Pars tuberalis

– Pars intermedia

40



Median eminence

– Swelling near attachment of infundibulum

– Where hypothalamic neurons release regulatory

hormones into interstitial fluids

• Hormones then enter bloodstream through

fenestrated capillaries (fenestra = window)

41



Portal vessels

– Blood vessels that link two capillary networks

– Entire complex is a portal system

– Hypophyseal portal system

• Ensures that regulatory hormones reach cells in

anterior pituitary before entering general circulation

42

Figure 18–7 The Hypophyseal Portal System and the Blood Supply to the Pituitary Gland.

Supra-optic nuclei Paraventricular nuclei Neurosecretory neurons

Mammillary

body

The superior hypophyseal artery delivers

blood to a capillary network in the upper

infundibulum.

Optic

chiasm

Capillary network

Infundibulum The portal vessels deliver blood containingregulatory hormones to the capillarynetwork in the anterior lobe of the pituitary.

The inferior hypophyseal artery delivers

blood to the posterior lobe of the pituitary

gland.

Hypophyseal veins carry blood containing

the pituitary hormones to the

cardiovascular system for delivery to the

rest of the body.

Anterior lobe of

the pituitary gland

Capillary network in

the anterior lobe

Posterior lobe of

the pituitary gland

Endocrine cells

43



Hypothalamic control of anterior lobe

– Two classes of hypothalamic regulatory hormones

• Releasing hormones (RH)

– Stimulate synthesis and secretion of one or more

hormones at anterior lobe

• Inhibiting hormones (IH)

– Prevent synthesis and secretion of hormones

from anterior lobe

– Rate of secretion is controlled by negative feedback

44

Figure 18–8a Feedback Control of Endocrine Secretion.

Typical pattern of regulation when multiple endocrine organs are involved

The hypothalamus produces a releasing hormone (RH) to stimulate hormone production by other glands. Homeostatic

control occurs by negative feedback.

HypothalamusKEY

Stimulation

Inhibition

The effects of hypothalamic releasing hormones that follow the typical pattern of

regulation

RH

Pituitary

gland

Releasing

hormone (RH) TRH CRH GnRH

Anterior

lobe

Hormone 1

Negative

feedbackHormone 1

(from pituitary)

Endocrine

target organ

TSH ACTH FSH LH

Endocrine

organ

Hormone 2

Thyroid

gland

Adrenal

cortexTestes Testes Ovaries

Hormone 2

(from endocrine

target organ)

Thyroid

hormonesGlucocorticoids Inhibin

Inhibin

Estrogens

Progesterone

EstrogensAndrogens

Ovaries

a

Target cells

45



Hormones of anterior lobe

– Thyroid-stimulating hormone (TSH)

– Adrenocorticotropic hormone (ACTH)

• Released due to corticotropin-releasing hormone

(CRH)

– Prolactin (PRL)

• Release inhibited by prolactin-inhibiting hormone

(PIH)

• Release stimulated by prolactin-releasing

hormone (PRH)

– Growth hormone (GH), or somatotropin

– Gonadotropins

46



Gonadotropins

– Follicle-stimulating hormone (FSH)

– Luteinizing hormone (LH)

• In females, it induces ovulation and stimulates

secretion of estrogens and progesterone

• In males, it stimulates production of androgens

– Production of FSH and LH is stimulated by

gonadotropin-releasing hormone (GnRH)

– Hypogonadism

• Caused by low production of gonadotropins

47

Figure 18–9 Pituitary Hormones and Their Targets (Part 1 of 2).

Hypothalamus

Direct Control

by Nervous

System

Indirect Control through Release

of Regulatory Hormones

Regulatory hormones are released

into the hypophyseal portal system

for delivery to the anterior lobe of the

pituitary gland

KEY TO PITUITARY HORMONES:

ACTH

TSH

GH

PRL

FSH

LH

MSH

ADH

OXT



Growth hormone

Prolactin


Luteinizing hormone


Antidiuretic hormone

Oxytocin

Adrenal

medulla

Adrenal

glandAdrenal

cortex

Anterior lobe of

pituitary gland

ACTH

TSH

Liver

PRL

Somatomedins

LH

GH

Epinephrine and

norepinephrineThyroid

gland

MSH

Glucocorticoids

(cortisol,

corticosterone)

Bone, muscle,

other tissues Mammary

glands

Thyroid

hormones (T3, T4)

Inhibin

Testes

of male

Ovaries

of female

Melanocytes (uncertain

significance in healthy

adults)

Testosterone Estrogen Progesterone Inhibin

FSH

48

Figure 18–8a Feedback Control of Endocrine Secretion.

49

Figure 18–8b Feedback Control of Endocrine Secretion.

Variations on the typical pattern of regulation of endocrine

organs by the hypothalamus and anterior pituitary lobe

The regulation ofprolactin (PRL)production bythe anterior lobe.In this case, thehypothalamusproduces both areleasing hormone(PRH) and aninhibiting hormone(PIH). When one isstimulated, theother is inhibited.

PIH

PRH

Stimulation

Inhibition

Anteriorlobe

PRL

Stimulates

mammary

glands

b

50



Growth hormone stimulates

– Liver cells to release somatomedins that stimulate

tissue growth

• Somatomedins cause skeletal muscle fibers and

other cells to increase uptake of amino acids

– Stem cells in epithelia and connective tissues to divide

– Breakdown of triglycerides in adipocytes, which leads

to glucose-sparing effect

– Breakdown of glycogen by liver cells causing

diabetogenic effect

51



Production of growth hormone is regulated by

– Growth hormone–releasing hormone (GH–RH)

– Growth hormone–inhibiting hormone (GH–IH)

52

Figure 18–8c Feedback Control of Endocrine Secretion.

Variations on the typical pattern of regulation of endocrine

organs by the hypothalamus and anterior pituitary lobe

The regulation of growth

hormone (GH) production

by the anterior lobe.

When GH–RH release is

inhibited, GH–IH release

is stimulated.

GH–IH

GH–RH

Stimulation

Inhibition

Anterior

lobe

GH

Liver

Somatomedins

Stimulate growth of skeletal muscle,

cartilage, and many other tissues

Epithelia,

adipose tissue,

liver

c

53



Pars intermedia

– Secretes melanocyte-stimulating hormone (MSH)

• Stimulates melanin production

– Virtually nonfunctional in adults except in

• Pregnant women

• Those with certain diseases

54



Posterior lobe of the pituitary gland

– Also called neurohypophysis

– Contains unmyelinated axons of hypothalamic neurons

– Supra-optic and paraventricular nuclei manufacture

(respectively)

• Antidiuretic hormone (ADH)

• Oxytocin (OXT)

– Stimulates contraction of uterus during labor

– Promotes ejection of milk after delivery

55

Figure 18–9 Pituitary Hormones and Their Targets (Part 2 of 2).

Hypothalamus

Direct Release

of Hormones

Sensory

stimulation


ACTH

TSH

GH

PRL

FSH

LH

MSH

ADH

OXT



Growth hormone

Prolactin


Luteinizing hormone



Oxytocin

Posterior lobe

of pituitary gland

ADH

OXTKidneys

Males: Smooth

muscle in ductus

deferens and

prostate gland

Females: Uterine

smooth muscle and

mammary glands

Osmoreceptor

stimulation

56

Figure 18–9 Pituitary Hormones and Their Targets.

Hypothalamus

Direct Control

by Nervous

System

Indirect Control through Release

of Regulatory Hormones

Direct Release

of Hormones


ACTH

TSH

GH

PRL

FSH

LH

MSH

ADH

OXT



Growth hormone

Prolactin


Luteinizing hormone



Oxytocin

Regulatory hormones are released

into the hypophyseal portal system

for delivery to the anterior lobe of the

pituitary gland

Sensory

stimulation

Adrenal

medulla

Adrenal

glandAdrenal

cortex

Thyroid

gland

Anterior lobe of

pituitary gland

ACTH

TSH

Liver

PRL

Somatomedins

LH

GH

Posterior lobe

of pituitary gland

ADH

OXT

MSH

Kidneys

Males: Smooth

muscle in ductus

deferens and

prostate gland

Females: Uterine

smooth muscle and

mammary glands

Epinephrine and

norepinephrine

Glucocorticoids

(cortisol,

corticosterone)

Bone, muscle,

other tissues

Thyroid

hormones (T3, T4)

Inhibin

Testes

of male

Ovaries

of female

Melanocytes (uncertain

significance in healthy

adults)

Testosterone Estrogen Inhibin

Osmoreceptor

stimulation

Mammary

glands

FSH

Progesterone

57


18-4 The Thyroid Gland

Thyroid gland

– Lies inferior to thyroid cartilage of larynx

– Consists of two lobes connected by narrow isthmus

• Thyroid follicles

– Hollow spheres lined by cuboidal epithelium

– Surrounded by capillaries

– Cells absorb iodide ions (I–) from blood

– Follicle cavity contains viscous colloid

• C (clear) cells, or parafollicular cells

58

Figure 18–10a Anatomy of the Thyroid Gland.

Hyoid bone

Superior

thyroid artery

Thyroid cartilage

of larynx

Superior

thyroid vein

Common

carotid artery

Right lobe of

thyroid gland

Middle thyroid

vein

Thyrocervical

trunk

Trachea

Outline of

clavicle

Outline of

sternum

Location and anatomy of the thyroid gland

Internal

jugular vein

Cricoid cartilage

of larynx

Left lobe of

thyroid gland

Isthmus of

thyroid gland

Inferior

thyroid artery

Inferior

thyroid

veins

a 59

Figure 18–10b Anatomy of the Thyroid Gland.

Thyroid follicles

The thyroid gland LM × 122

Histological organization of the thyroidb 60

Figure 18–10c Anatomy of the Thyroid Gland.

Capillary

Capsule

Follicle

cavities

Thyroid

follicle

C cell

Cuboidal

epithelium

of follicle

Thyroglobulin

stored in colloid

of follicle

Thyroid

follicle

C cell

Follicles of the thyroid gland LM × 260

Histological details of the thyroid gland showing thyroid follicles and both celltypes in the follicular epithelium ATLAS: Plate 18c

c

61



Thyroglobulin

– Globular protein synthesized by follicle cells

– Secreted into colloid of thyroid follicles

– Contains the amino acid tyrosine

• The building block of thyroid hormones

Thyroid hormones

– Thyroxine (T4), or tetraiodothyronine

• Contains four iodine atoms

– Triiodothyronine (T3)

• Contains three iodine atoms

62

Figure 18–11a Synthesis and Regulation of Thyroid Hormones.

1

Thyroglobulin

(contains T3 and T4)

4

2

Iodineatoms (I0)

Thyroglobulin

5

Follicle cavity

Iodide ions are absorbed from the digestive tract and

delivered to the thyroid gland by the bloodstream.

2

Endocytosis Iodide ions diffuse to the apical surface of each follicle cell

where they are converted into an atom of iodine (I0). The

tyrosine portion of thyroglobulin bind the iodine atoms.

3

Iodine-containing thyroxine molecules become linked to

form thyroid hormones (T3 and T4)

4

Follicle cells remove thyroglobulin from the follicles by

endocytosis.

Diffusion 5

Lysosomal enzymes break down the thyroglobulin, and the

amino acids and thyroid hormones enter the cytoplasm.

7

CAPILLARY

6

The released T3 and T4 diffuse from the follicle cell into

the bloodstream.

7

A majority of the T3 and T4 bind to transport proteins.

Folliclecavity

Other amino acids

Tyrosine

Lysosomal

digestion

T4

T3

Diffusion

TSH-

sensitive

ion pump1

Follicle cell

Iodide ions (I–)

T4 & T3

The synthesis, storage, and secretion of thyroid hormones.

TBG, transthyretin,

or albumin

3

6

a

63

Figure 18–11b Synthesis and Regulation of Thyroid Hormones.

HOMEOSTASISHomeostasis

DISTURBED BY

DECREASING

T3 and T4

concentrations

in blood or low

body temperature

Normal T3 and T4 concentrations,

normal body temperatureHomeostasis

RESTORED BY

STIMULUS

Receptor

Hypothalamus

RESTOREDINCREASING

T3 and

T4 concentrations

in blood

Anterior lobe T3 and T4

concentrations increase

in blood and body

temperature rises

TRH Effector

Anterior

lobe

TSH

Anterior

lobe Thyroid

gland

Thyroid follicles

release T3 and T4

Hypothalamus

releases TRHAnterior lobe

releases TSH

The regulation of thyroid secretion.b

64



Thyroid-binding globulins (TBGs)

– Proteins that bind about 75 percent of T4 and 70

percent of T3 entering the bloodstream

Transthyretin and albumin

– Bind most of the remaining thyroid hormones

About 0.3 percent of T3 and 0.03 percent of T4 remain

unbound and free to diffuse into tissues

65



Thyroid-stimulating hormone (TSH)

– Absence causes thyroid follicles to become inactive

• Neither synthesis nor secretion occurs

– Binds to plasma membrane receptors

• Activates key enzymes in thyroid hormone

production

66



Thyroid hormones

– Affect almost every cell in body

– Enter target cells by transport system

– Bind to receptors

• In cytoplasm

• On surfaces of mitochondria

• In nucleus

– In children, essential to normal development of

skeletal, muscular, and nervous systems

67



Thyroid hormones activate genes involved in glycolysis

and ATP production

– Results in calorigenic effect

• Increased energy consumption and heat generation

of cells

• Responsible for strong, immediate, and short-lived

increase in rate of cellular metabolism

68



C cells

– Produce calcitonin (CT)

• Helps regulate concentrations of Ca2+ in body fluids

• Stimulates Ca2+ excretion by kidneys

• Prevents Ca2+ absorption by digestive tract

69



Effects of thyroid hormones

– Elevate oxygen and energy consumption; in children,

may cause rise in body temperature

– Increase heart rate and force of contraction

– Increase sensitivity to sympathetic stimulation

– Maintain normal sensitivity of respiratory centers to

oxygen and carbon dioxide concentrations

– Stimulate red blood cell formation

– Stimulate activity in other endocrine tissues

– Accelerate turnover of minerals in bone

70


18-5 Parathyroid Glands

Parathyroid glands

– Two pairs

– Embedded in posterior surface of thyroid gland

– Altogether, the four glands weigh 1.6 g

Parathyroid hormone (PTH) or parathormone

– Secreted by parathyroid (principal) cells in response

to low concentrations of Ca2+ in blood

– Antagonist for calcitonin

71

Figure 18–12a Anatomy of the Parathyroid Glands.

Left lobe of

thyroid gland

Parathyroid

glands

Thyroid gland, posterior view.

The location of the parathyroid glands

on the posterior surface of the thyroid

lobes. (The thyroid lobes are located

anterior to the trachea.)

a

72

Figure 18–12b Anatomy of the Parathyroid Glands.

Blood vessel

Connectivetissue capsuleof parathyroid

gland

Thyroid

follicle

Parathyroid gland

Both parathyroid and thyroid tissues.

LM × 94

b

73

Figure 18–12c Anatomy of the Parathyroid Glands.

Parathyroid(principal)cells

Oxyphil cells

Parathyroid cells and oxyphil cells

Parathyroid gland cells.

LM × 600

c

74


18-5 Parathyroid Glands

Major effects of parathyroid hormone

– Stimulates osteoclasts

• Accelerates mineral turnover and Ca2+ release

– Enhances reabsorption of Ca2+ by kidneys, reducing

urinary losses

– Stimulates formation and secretion of calcitriol by

kidneys

75

Figure 18–13 Homeostatic Regulation of the Blood Calcium Ion Concentration (Part 1 of 2) .

76

Figure 18–13 Homeostatic Regulation of the Blood Calcium Ion Concentration (Part 2 of 2) .

77


18-6 Adrenal Glands

Adrenal glands

– Lie along superior border of each kidney

– Superficial adrenal cortex

• Stores lipids, especially cholesterol and fatty acids

• Manufactures steroid hormones (corticosteroids)

– Inner adrenal medulla

• Secretory activities controlled by sympathetic

division of ANS

• Produces epinephrine and norepinephrine

(catecholamines)

78

Figure 18–14a The Adrenal Gland and Adrenal Hormones.

Right superior

adrenal arteries

Celiac trunk

Right adrenal gland

Right middle

adrenal artery

Right inferior

adrenal artery

Right renal artery

Right renal vein

Right and left inferior

phrenic arteries

Left adrenal gland

Left middle

adrenal artery

Left inferior

adrenal arteries

Left adrenal vein

Left renal artery

Left renal vein

Superior

mesenteric artery

Abdominal aorta

Inferior vena cava

A superficial view of the kidneys

and adrenal glands

a

79


18-6 Adrenal Glands

Adrenal cortex

– Subdivided into three zones

• Outer zona glomerulosa

• Middle zona fasciculata

• Inner zona reticularis

80


18-6 Adrenal Glands

Zona glomerulosa

– Outer region of adrenal cortex

– Produces mineralocorticoids (e.g., aldosterone)

– Aldosterone

• Stimulates conservation of sodium ions and

elimination of potassium ions

• Increases sensitivity of salt receptors in taste buds

• Secreted in response to

– Drop in blood Na+, blood volume, or blood

pressure

– Rise in blood K+ concentration

81


18-6 Adrenal Glands

Zona fasciculata

– Produces glucocorticoids

• Example: cortisol, corticosterone, and cortisone

• Secretion is regulated by negative feedback

– Glucocorticoids have inhibitory effect on production of

• Corticotropin-releasing hormone (CRH) in

hypothalamus

• ACTH in anterior pituitary

82


18-6 Adrenal Glands

Effects of glucocorticoids

– Accelerate glucose synthesis and glycogen formation,

especially in liver

– Have anti-inflammatory effects

• Inhibit activities of white blood cells and other

components of immune system

83


18-6 Adrenal Glands

Zona reticularis

– Branching network of endocrine cells

– Forms narrow band bordering each adrenal medulla

– Produces small quantities of androgens under

stimulation by ACTH

• Some are converted to estrogens in bloodstream

• Stimulate development of pubic hair before puberty

84

Figure 18–14b The Adrenal Gland and Adrenal Hormones.

Capsule

Cortex

Medulla

An adrenal glandin section

b

85

Figure 18–14c The Adrenal Gland and Adrenal Hormones.

The Adrenal Hormones

Region/Zone

Adrenal capsule

Zona

glomerulosa

Hormones

Mineralocorticoids,primarilyaldosterone

Primary

Target

Kidneys

Hormonal Effects

Increase renal reabsorptionof Na+ and water (especiallyin the presence of ADH),and accelerate urinary lossof K+

Increase rates of glucoseand glycogen formationby the liver; release ofamino acids from skeletalmuscles, and lipids fromadipose tissues; promoteperipheral utilization oflipids; anti-inflammatoryeffects

Regulatory Control

Stimulated by angiotensin II,elevated blood K+ or fall inblood Na+; inhibited by ANPand BNP

Stimulated by ACTH fromthe anterior lobe of thepituitary gland

Zona

fasciculata

Adrenal

cortex

Glucocorticoids

(cortisol, corti-

costerone, and

cortisone)

Most cells

Androgens

Zona

reticularis

Most cells Adrenal androgens stimulatethe development of pubichair in boys and girls beforepuberty.

Increases cardiac activity,blood pressure, glycogenbreakdown, blood glucoselevels; releases lipids byadipose tissue

Stimulated by sympathetic

preganglionic fibers

Epinephrine (E),

norepinephrine

(NE)

Adrenal

medulla

Adrenal gland LM × 140

Most cells

The major regions and zones of an adrenal gland and the hormones they produce

Androgen secretion

is stimulated by

ACTH.

c

86


18-6 Adrenal Glands

Adrenal medulla

– Contains two types of secretory cells

• One produces epinephrine (E)

– 75–80 percent of medullary secretion

• The other produces norepinephrine (NE)

– 20–25 percent of medullary secretion

87


18-6 Adrenal Glands

Results of activation of adrenal medulla

– In skeletal muscles, E and NE trigger mobilization of

glycogen reserves

• And accelerate breakdown of glucose

– In adipose tissue, stored fats are broken down into fatty

acids

– In the liver, glycogen molecules are broken down

– In the heart, stimulation of β1 receptors speeds and

strengthens cardiac muscle contraction

88


18-7 Pineal Gland

Pineal gland

– Lies in posterior portion of roof of third ventricle

– Contains pinealocytes

• Synthesize hormone melatonin

– Functions of melatonin

• Influence circadian rhythms

• Inhibit reproductive functions

• Protect against damage by free radicals

89

Figure 18–15 Anatomy of the Pineal Gland.

Pinealocytes

Pineal gland LM × 280

90


18-8 Pancreas

Pancreas

– Large gland

– Lies in loop between inferior border of stomach and

proximal portion of small intestine

– Mostly retroperitoneal

– Contains exocrine and endocrine cells

91

Figure 18–16a Anatomy of the Pancreas.

Common

bile duct

Accessorypancreatic

duct

Head of

pancreas

Pancreatic

duct

Body of

pancreasLobule Tail

Small

intestine

(duodenum)

The gross anatomy of the pancreasa

92


18-8 Pancreas

Exocrine pancreas

– Consists of clusters of gland cells called pancreatic

acini and their attached ducts

– Takes up roughly 99 percent of pancreatic volume

– Gland and duct cells secrete alkaline, enzyme-rich fluid

• Passes through a network of ducts to lumen of

digestive tract

93


18-8 Pancreas

Endocrine pancreas

– Consists of cells that form clusters known as

pancreatic islets (islets of Langerhans)

• Alpha (α) cells produce glucagon

• Beta (β) cells produce insulin

• Delta (δ) cells produce peptide hormone identical to

GH–IH

• Pancreatic polypeptide cells (PP cells) produce

pancreatic polypeptide (PP)

94

Figure 18–16b Anatomy of the Pancreas.

Pancreatic islet

(islet of Langerhans)

Capillary

Pancreatic islet LM × 400

A pancreatic islet surrounded by

exocrine cells

b

Pancreatic acini

(clusters ofexocrine cells)

95


18-8 Pancreas

When blood glucose level increases

– Beta cells secrete insulin

• Stimulating transport of glucose into target cells

When blood glucose level decreases

– Alpha cells secrete glucagon

• Stimulating glycogen breakdown and glucose

release by liver

96

Figure 18–17 Homeostatic Regulation of the Blood Glucose Concentration (Part 1 of 2).

97

Figure 18–17 Homeostatic Regulation of the Blood Glucose Concentration (Part 2 of 2).

98


18-8 Pancreas

Insulin

– Peptide hormone released by beta cells

– Effects on target cells

• Accelerating glucose uptake

• Accelerating glucose use and enhancing ATP

production

• Stimulating glycogen formation

• Stimulating amino acid absorption and protein

synthesis

• Stimulating triglyceride formation in adipocytes

99


18-8 Pancreas

Glucagon

– Released by alpha cells

– Mobilizes energy reserves

– Effects on target cells

• Stimulating breakdown of glycogen in skeletal

muscle fibers and liver cells

• Stimulating breakdown of triglycerides in adipocytes

• Stimulating production and release of glucose in

liver cells (gluconeogenesis)

100


18-8 Pancreas

Hyperglycemia

– Abnormally high glucose levels in the blood

Diabetes mellitus

– Characterized by high glucose concentrations that

overwhelm reabsorption capabilities of kidneys

– Glucose appears in urine

– Polyuria

• Urine volume becomes excessive

101


18-8 Pancreas

Type 1 diabetes mellitus

– Characterized by inadequate insulin production by

pancreatic beta cells

– Patients require daily injections or continuous infusion

of insulin

– Approximately 5 percent of cases

– Usually develops in children and young adults

102


18-8 Pancreas

Type 2 diabetes mellitus

– Most common form

– Usually, normal amounts of insulin are produced, at

least initially

• Tissues do not respond properly (insulin resistance)

– Associated with obesity

• Weight loss can be an effective treatment

103


18-8 Pancreas

Complications of untreated or poorly managed diabetes

mellitus include

– Kidney degeneration

– Retinal damage (diabetic retinopathy)

• May lead to blindness

– Early heart attacks (3–5 times more likely)

– Peripheral nerve problems (diabetic neuropathies)

– Peripheral tissue damage due to reduced blood flow

• Tissue death, ulceration, infection, and amputation

104


18-9 Secondary Endocrine Functions

Organs with secondary endocrine functions

– Intestines (digestive system)

– Kidneys (urinary system)

– Heart (cardiovascular system)

– Thymus (lymphatic system)

– Gonads (reproductive system)

105



Intestines

– Release hormones that coordinate digestive activities

Kidneys

– Release the hormones calcitriol and erythropoietin

(EPO)

– Release the enzyme renin

• Renin converts angiotensinogen to angiotensin I

• In the lungs, angiotensin-converting enzyme

converts angiotensin I to angiotensin II

106

Figure 18–19a Endocrine Functions of the Kidneys.

SunlightFood

Cholesterol

Epidermis

Cholecalciferol

Dietarycholecalciferol

Liver

Intermediateform

Parathyroid glands

Digestivetract

Stimulation ofcalcium and

phosphate ionabsorption

PTH

Calcitriol

Kidney

The production of calcitriola 107

Figure 18–19b Endocrine Functions of the Kidneys.

Homeostasis

DISTURBED BY

DECREASING

blood pressure

and

volume

HOMEOSTASISNormal blood pressure and volume Homeostasis

RESTORED BY

INCREASING

blood pressure

and

volume

STIMULUS

Receptor

Kidney

RESTORED

Increase in blood

pressure and volume

Endocrine Response

of Kidneys

Decreasing

renal blood

flow and O2

Increased fluid intake

and retention

Increased

red blood cell

production

Erythropoietin (EPO)

is released

Renin is released

Aldosterone secreted

ADH secreted

Stimulation of thirst

Angiotensinogen Angiotensin IACE

Angiotensin II

The release of renin and erythropoietin, and an overview of the renin-angiotensin-aldosterone

system beginning with the activation of angiotensinogen by reninb

108



Heart

– Produces natriuretic peptides (ANP and BNP)

• When blood volume becomes excessive

• Actions opposes those of angiotensin II

• Resulting in reduction in blood volume and blood

pressure

Thymus

– Produces thymosin (blend of several hormones)

• Promotes development and maturation of

lymphocytes

109



Testes

– Interstitial endocrine cells produce androgens

• Testosterone is an important androgen

– Nurse cells (Sertoli cells)

• Support differentiation and physical maturation of

sperm

• Secrete inhibin for negative feedback

110



Ovaries

– Produce estrogens

• Principal estrogen is estradiol

– After ovulation, follicle cells

• Reorganize into corpus luteum

• Release estrogens and progesterone

111



Adipose tissue

– Produces leptin (a peptide hormone)

• Provides feedback control of appetite

• Maintains normal levels of GnRH and gonadotropin

synthesis

112


18-10 Hormone Interactions

When a cell receives instructions from two hormones at

the same time, four outcomes are possible

– Antagonistic effect

• Result depends on balance between two hormones

– Synergistic effect

• Additive effect

– Permissive effect

• One hormone is needed for another to produce

effect

– Integrative effect

• Hormones produce different but complementary

results

113



Hormones important to growth

– Growth hormone

– Thyroid hormones

– Insulin

– Parathyroid hormone and calcitriol

– Reproductive hormones

114



Growth hormone (GH)

– In children

• Supports muscular and skeletal development

– In adults

• Maintains normal blood glucose concentrations

• Mobilizes lipid reserves

115



Thyroid hormones

– If absent during fetal development or for first year after

birth

• Nervous system fails to develop normally

• Developmental delay results

– If T4 concentrations decline before puberty

• Normal skeletal development does not continue

116



Insulin

– Allows passage of glucose and amino acids across

plasma membranes

– Important for growing cells

Parathyroid hormone (PTH) and calcitriol

– Promote absorption of calcium salts from bloodstream

for deposition in bone

– Inadequate levels result in weak, flexible bones

117



Reproductive hormones

– Androgens in males, estrogens in females

– Stimulate cell growth and differentiation in target

tissues

– Produce gender-related differences in

• Skeletal proportions

• Secondary sex characteristics

118



Stress

– Any condition that threatens homeostasis

– General adaptation syndrome (GAS)

• Also called stress response

• How body responds to stress-causing factors

• Divided into three phases

– Alarm phase

– Resistance phase

– Exhaustion phase

119



General adaptation syndrome

– Alarm phase

• Immediate response to stress

• Directed by sympathetic division of ANS

• Energy reserves (mainly glucose) are mobilized

• Body prepares “fight or flight” responses

• Epinephrine is dominant hormone

120




– Resistance phase

• Occurs if stress lasts longer than a few hours

• May last for weeks or months

• Glucocorticoids are dominant hormones

• Lipids and amino acids are mobilized for energy

• Glucose is conserved for use by nervous tissue

121




– Exhaustion phase

• Begins when homeostatic regulation breaks down

• Drop in K+ levels due to aldosterone produced in

resistance phase

• Failure of one or more organ systems will be fatal

122



Hormone changes

– Can affect behavior, intellectual capabilities, memory,

learning, and emotional states

Few functional changes occur with age

– Reproductive hormones decline in concentration

– Some endocrine tissues become less responsive to

stimulation

123

Figure 18–21 Integration of the ENDOCRINE system with the other body systems presented so far.

Integumentary System

• The endocrine system secretes sex

hormones that stimulate sebaceous

gland activity, influence hair growth,

fat distribution, and apocrine sweat

gland activity; PRL that stimulates

development of mammary glands;

adrenal hormones that alter dermal

blood flow; MSH that stimulates

melanocyte activity

Nervous System

• The Nervous System produces

hypothalamic hormones that directly

control pituitary secretions and

indirectly control secretions of other

endocrine organs; controls adrenal

medulla; secretes ADH and oxytocin

• The endocrine system secretes

several hormones that affect neural

metabolism and brain development;

hormones that help regulate fluid and

electrolyte balance; reproductive

hormones that influence CNS

development and behaviors

Skeletal System

• The Skeletal System protects

endocrine organs, especially in brain,

chest, and pelvic cavity

• The endocrine system regulates

skeletal growth with several

hormones; calcium homeostasis

regulated primarily by parathyroid

hormone; sex hormones speed

growth and closure of epiphyseal

cartilages at puberty and help

maintain bone mass in adults

Endocrine System

The endocrine system provides

long-term regulation and adjustments

of homeostatic mechanisms that affect

many body functions. It:

• regulates fluid and electrolyte

balance

• regulates cell and tissue metabolism

• regulates growth and development

• regulates reproductive functions

• responds to stressful stimuli through

the general adaptation syndrome

(GAS)

Muscular System

• The Muscular System provides

protection for some endocrine

organs

• The endocrine system secretes

hormones that adjust muscle

metabolism, energy production,

and growth; regulate calcium and

phosphate levels in body fluids;

speed skeletal muscle growth

124

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