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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

​

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Endocrine System: Overview

  • 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

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Endocrine System: Overview

  • Exocrine glands
    • Nonhormonal substances (sweat, saliva)
    • Have ducts to carry secretion to membrane surface
  • Endocrine glands
    • Produce hormones
    • Lack ducts

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Endocrine System: Overview

  • 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

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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

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Chemistry of Hormones

  • Two main classes
    • Amino acid-based hormones
      • Amino acid derivatives, peptides, and proteins
    • Steroids
      • Synthesized from cholesterol
      • Gonadal and adrenocortical hormones
  • Third: Eicosanoids: 1-Leukotrienes. 2-Prostoglandins. 3- Thromboxanes

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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

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Mechanisms of Hormone Action

  • 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

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Mechanisms of Hormone Action

  • Hormones act at receptors in one of two ways, depending on their chemical nature and receptor location
    1. 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

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Mechanisms of Hormone Action

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

      • Act on intracellular receptors that directly activate genes
      • Can enter cell

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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

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Plasma Membrane Receptors and Second-messenger Systems

  • 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

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

© 2013 Pearson Education, Inc.

Slide 2

Recall from Chapter 3 that

G protein signaling mechanisms

are like a molecular relay race.

Hormone

(1st messenger)

Receptor

G protein

Enzyme

2nd

messenger

Hormone (1st messenger) binds receptor.

1

Extracellular fluid

Receptor

Cytoplasm

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

© 2013 Pearson Education, Inc.

Slide 3

Recall from Chapter 3 that

G protein signaling mechanisms

are like a molecular relay race.

Hormone

(1st messenger)

Receptor

G protein

Enzyme

2nd

messenger

Extracellular fluid

Hormone (1st messenger) binds receptor.

1

G protein (Gs)

GDP

Receptor

GTP

GTP

Receptor activates G protein (Gs).

2

Cytoplasm

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

© 2013 Pearson Education, Inc.

Slide 4

Recall from Chapter 3 that

G protein signaling mechanisms

are like a molecular relay race.

Hormone

(1st messenger)

Receptor

G protein

Enzyme

2nd

messenger

Adenylate cyclase

Extracellular fluid

G protein (Gs)

GDP

Receptor

Hormone (1st messenger) binds receptor.

Receptor activates G protein (Gs).

G protein activates adenylate cyclase.

Cytoplasm

GTP

GTP

GTP

1

2

3

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

© 2013 Pearson Education, Inc.

Slide 5

Recall from Chapter 3 that

G protein signaling mechanisms

are like a molecular relay race.

Hormone

(1st messenger)

Receptor

G protein

Enzyme

2nd

messenger

Adenylate cyclase

Extracellular fluid

G protein (Gs)

GDP

Receptor

Hormone (1st messenger) binds receptor.

Receptor activates G protein (Gs).

G protein activates adenylate cyclase.

Adenylate

cyclase converts

ATP to cAMP (2nd messenger).

Cytoplasm

cAMP

GTP

GTP

GTP

ATP

1

2

3

4

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

© 2013 Pearson Education, Inc.

Slide 6

Recall from Chapter 3 that

G protein signaling mechanisms

are like a molecular relay race.

Hormone

(1st messenger)

Receptor

G protein

Enzyme

2nd

messenger

Adenylate cyclase

Extracellular fluid

G protein (Gs)

GDP

Receptor

Hormone (1st messenger) binds receptor.

Receptor activates G protein (Gs).

G protein activates adenylate cyclase.

Adenylate

cyclase converts

ATP to cAMP (2nd messenger).

Inactive

protein

kinase

Triggers responses of

target cell (activates

enzymes, stimulates

cellular secretion,

opens ion channel, etc.)

Active

protein

kinase

cAMP activates protein kinases.

Cytoplasm

cAMP

GTP

GTP

GTP

ATP

1

2

3

4

5

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Intracellular Receptors and Direct Gene Activation

  • Steroid hormones and thyroid hormone
    1. Diffuse into target cells and bind with intracellular receptors
    2. Receptor-hormone complex enters nucleus; binds to specific region of DNA
    3. Prompts DNA transcription to produce mRNA
    4. mRNA directs protein synthesis
    5. Promote metabolic activities, or promote synthesis of structural proteins or proteins for export from cell

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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

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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

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© 2013 Pearson Education, Inc.

Figure 16.4a Three types of endocrine gland stimuli.

Slide 1

Humoral Stimulus

Hormone release caused by altered

levels of certain critical ions or

nutrients.

Stimulus: Low concentration of Ca2+ in

capillary blood.

Parathyroid

glands

Parathyroid

glands

Capillary (low Ca2+

in blood)

Thyroid gland

(posterior view)

PTH

Response: Parathyroid glands secrete

parathyroid hormone (PTH), which

increases blood Ca2+.

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© 2013 Pearson Education, Inc.

Figure 16.4a Three types of endocrine gland stimuli.

Slide 2

Humoral Stimulus

Hormone release caused by altered

levels of certain critical ions or

nutrients.

Parathyroid

glands

Parathyroid

glands

Capillary (low Ca2+

in blood)

Thyroid gland

(posterior view)

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© 2013 Pearson Education, Inc.

Figure 16.4a Three types of endocrine gland stimuli.

Slide 1

Humoral Stimulus

Hormone release caused by altered

levels of certain critical ions or

nutrients.

Stimulus: Low concentration of Ca2+ in

capillary blood.

Parathyroid

glands

Parathyroid

glands

Capillary (low Ca2+

in blood)

Thyroid gland

(posterior view)

PTH

Response: Parathyroid glands secrete

parathyroid hormone (PTH), which

increases blood Ca2+.

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Neural Stimuli

  • Nerve fibers stimulate hormone release
    • Sympathetic nervous system fibers stimulate adrenal medulla to secrete catecholamines

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© 2013 Pearson Education, Inc.

Figure 16.4b Three types of endocrine gland stimuli.

Slide 1

Neural Stimulus

Hormone release caused �by neural input.

Stimulus: Action potentials in preganglionic

sympathetic fibers to adrenal medulla.

CNS (spinal cord)

Preganglionic

sympathetic

fibers

Medulla of

adrenal gland

Capillary

Response: Adrenal medulla cells secrete

epinephrine and norepinephrine.

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© 2013 Pearson Education, Inc.

Figure 16.4b Three types of endocrine gland stimuli.

Slide 2

Neural Stimulus

Hormone release caused �by neural input.

CNS (spinal cord)

Preganglionic

sympathetic

fibers

Medulla of

adrenal gland

Capillary

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© 2013 Pearson Education, Inc.

Figure 16.4b Three types of endocrine gland stimuli.

Slide 3

Neural Stimulus

Hormone release caused �by neural input.

Stimulus: Action potentials in preganglionic

sympathetic fibers to adrenal medulla.

CNS (spinal cord)

Preganglionic

sympathetic

fibers

Medulla of

adrenal gland

Capillary

Response: Adrenal medulla cells secrete

epinephrine and norepinephrine.

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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

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© 2013 Pearson Education, Inc.

Figure 16.4c Three types of endocrine gland stimuli.

Slide 4

Hormonal Stimulus

Hormone release caused by another

hormone (a tropic hormone).

Stimulus: Hormones from hypothalamus.

Anterior

pituitary

gland

Thyroid

gland

Adrenal

cortex

Gonad

(Testis)

Hypothalamus

Response: Anterior pituitary gland secretes

hormones that stimulate other endocrine �glands to secrete hormones.

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© 2013 Pearson Education, Inc.

Figure 16.4c Three types of endocrine gland stimuli.

Slide 1

Hormonal Stimulus

Hormone release caused by another

hormone (a tropic hormone).

Stimulus: Hormones from hypothalamus.

Anterior

pituitary

gland

Thyroid

gland

Adrenal

cortex

Gonad

(Testis)

Hypothalamus

Response: Anterior pituitary gland secretes

hormones that stimulate other endocrine �glands to secrete hormones.

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© 2013 Pearson Education, Inc.

Figure 16.4c Three types of endocrine gland stimuli.

Slide 2

Hormonal Stimulus

Hormone release caused by another

hormone (a tropic hormone).

Anterior

pituitary

gland

Thyroid

gland

Adrenal

cortex

Gonad

(Testis)

Hypothalamus

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© 2013 Pearson Education, Inc.

Figure 16.4c Three types of endocrine gland stimuli.

Slide 3

Hormonal Stimulus

Hormone release caused by another

hormone (a tropic hormone).

Anterior

pituitary

gland

Thyroid

gland

Adrenal

cortex

Gonad

(Testis)

Hypothalamus

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The Pituitary Gland and Hypothalamus

  • Pituitary gland (hypophysis) has two major lobes
    • Posterior pituitary (lobe)
      • Neural tissue
    • Anterior pituitary (lobe) (adenohypophysis)
      • Glandular tissue

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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

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© 2013 Pearson Education, Inc.

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

Slide 1

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.

1

2

3

4

Oxytocin

ADH

Posterior lobe

of pituitary

Optic

chiasma

Infundibulum

(connecting stalk)

Hypothalamic-

hypophyseal

tract

Axon terminals

Posterior lobe

of pituitary

Paraventricular nucleus

Hypothalamus

Supraoptic

nucleus

Inferior

hypophyseal

artery

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

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© 2013 Pearson Education, Inc.

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

Slide 2

Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH).

1

Posterior lobe

of pituitary

Optic

chiasma

Infundibulum

(connecting stalk)

Axon terminals

Paraventricular nucleus

Hypothalamus

Supraoptic

nucleus

Inferior

hypophyseal

artery

Hypothalamic-

hypophyseal

tract

Posterior lobe

of pituitary

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© 2013 Pearson Education, Inc.

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

Slide 3

Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH).

1

2

Posterior lobe

of pituitary

Optic

chiasma

Infundibulum

(connecting stalk)

Axon terminals

Paraventricular nucleus

Hypothalamus

Supraoptic

nucleus

Inferior

hypophyseal

artery

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

Hypothalamic-

hypophyseal

tract

Posterior lobe

of pituitary

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© 2013 Pearson Education, Inc.

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

Slide 4

Hypothalamic neurons synthesize oxytocin or antidiuretic hormone (ADH).

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

1

2

3

Posterior lobe

of pituitary

Optic

chiasma

Infundibulum

(connecting stalk)

Axon terminals

Paraventricular nucleus

Hypothalamus

Supraoptic

nucleus

Inferior

hypophyseal

artery

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

Hypothalamic-

hypophyseal

tract

Posterior lobe

of pituitary

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© 2013 Pearson Education, Inc.

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

Slide 5

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.

1

2

3

4

Oxytocin

ADH

Posterior lobe

of pituitary

Optic

chiasma

Infundibulum

(connecting stalk)

Axon terminals

Paraventricular nucleus

Hypothalamus

Supraoptic

nucleus

Inferior

hypophyseal

artery

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

Hypothalamic-

hypophyseal

tract

Posterior lobe

of pituitary

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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

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© 2013 Pearson Education, Inc.

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

Slide 1

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 lobe

of pituitary

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

Hypophyseal

portal system

• Primary capillary

plexus

• Hypophyseal

portal veins

• Secondary

capillary plexus

Superior

hypophyseal

artery

Anterior lobe

of pituitary

Hypothalamus

Hypothalamic

neurons synthesize

GHRH, GHIH, TRH,

CRH, GnRH, PIH.

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

1

2

3

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© 2013 Pearson Education, Inc.

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

Slide 2

GH, TSH, ACTH,

FSH, LH, PRL

Anterior lobe

of pituitary

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

Hypophyseal

portal system

• Primary capillary

plexus

• Hypophyseal

portal veins

• Secondary

capillary plexus

Superior

hypophyseal

artery

Anterior lobe

of pituitary

Hypothalamus

Hypothalamic

neurons synthesize

GHRH, GHIH, TRH,

CRH, GnRH, PIH.

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

1

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© 2013 Pearson Education, Inc.

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

Slide 3

Hypothalamic hormones travel through portal veins to the anterior pituitary where

they stimulate or inhibit

release of hormones made in the anterior pituitary.

GH, TSH, ACTH,

FSH, LH, PRL

Anterior lobe

of pituitary

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

Hypophyseal

portal system

• Primary capillary

plexus

• Hypophyseal

portal veins

• Secondary

capillary plexus

Superior

hypophyseal

artery

Anterior lobe

of pituitary

Hypothalamus

Hypothalamic

neurons synthesize

GHRH, GHIH, TRH,

CRH, GnRH, PIH.

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

1

2

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© 2013 Pearson Education, Inc.

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

Slide 4

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 lobe

of pituitary

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

Hypophyseal

portal system

• Primary capillary

plexus

• Hypophyseal

portal veins

• Secondary

capillary plexus

Superior

hypophyseal

artery

Anterior lobe

of pituitary

Hypothalamus

Hypothalamic

neurons synthesize

GHRH, GHIH, TRH,

CRH, GnRH, PIH.

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

1

2

3

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Anterior Pituitary Hormones

  • Growth hormone (GH)
  • Thyroid-stimulating hormone (TSH) or thyrotropin
  • Adrenocorticotropic hormone (ACTH)
  • Follicle-stimulating hormone (FSH)
  • Luteinizing hormone (LH)
  • Prolactin (PRL)

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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)

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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
    • In the liver it encourages Glycogen breakdown and glucose release to blood (anti-insulin effect)

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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

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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

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Homeostatic Imbalances of Growth Hormone

  • Hypersecretion
    • In children results in gigantism
    • In adults results in acromegaly
  • Hyposecretion
    • In children results in pituitary dwarfism

© 2013 Pearson Education, Inc.

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© 2013 Pearson Education, Inc.

Figure 16.7 Disorders of pituitary growth hormone.

Dwarfism, gigantism and normal female

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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

​

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Adrenocorticotropic Hormone (Corticotropin)

  • Secreted by corticotropic cells of anterior pituitary
  • Stimulates adrenal cortex to release corticosteroids

© 2013 Pearson Education, Inc.

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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

© 2013 Pearson Education, Inc.

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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

© 2013 Pearson Education, Inc.

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Gonadotropins

  • Regulation of gonadotropin release
    • Triggered by gonadotropin-releasing hormone (GnRH) during and after puberty
    • Suppressed by gonadal hormones (feedback)

© 2013 Pearson Education, Inc.

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Prolactin (PRL)

  • Secreted by prolactin cells of anterior pituitary
  • Stimulates milk production
  • Role in males not well understood

© 2013 Pearson Education, Inc.

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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.

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Thyroid Gland

  • Two lateral lobes connected by median mass called isthmus
  • Composed of follicles that produce glycoprotein thyroglobulin
  • Colloid (thyroglobulin + iodine) fills lumen of follicles and is precursor of thyroid hormone
  • Parafollicular cells produce the hormone calcitonin

© 2013 Pearson Education, Inc.

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Thyroid Hormone (TH)

  • Actually two related compounds
    • T4 (thyroxine); has 2 tyrosine molecules + 4 bound iodine atoms
    • T3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms
  • Affects virtually every cell in body

© 2013 Pearson Education, Inc.

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Thyroid Hormone

  • Major metabolic hormone
  • Increases metabolic rate and heat production (calorigenic effect)
  • Regulation of tissue growth and development
    • Development of skeletal and nervous systems
    • Reproductive capabilities
  • Maintenance of blood pressure

© 2013 Pearson Education, Inc.

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Synthesis of Thyroid Hormone

  • Thyroid gland stores hormone extracellularly
  • Thyroglobulin synthesized and discharged into follicle lumen
  • Iodides (I–) actively taken into cell and released into lumen
  • Iodide oxidized to iodine (I2),
  • Iodine attaches to tyrosine, mediated by peroxidase enzymes

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Synthesis of Thyroid Hormone

  • Iodinated tyrosines link together to form T3 and T4
  • Colloid is endocytosed and combined with lysosome
  • T3 and T4 are cleaved and diffuse into bloodstream

© 2013 Pearson Education, Inc.

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Figure 16.10 Synthesis of thyroid hormone.

© 2013 Pearson Education, Inc.

Slide 2

Thyroglobulin is synthesized and discharged into the follicle lumen.

1

Golgi

apparatus

Rough

ER

Capillary

Colloid in

lumen of

follicle

Thyroid follicular cells

Tyrosines (part of thyroglobulin

molecule)

Colloid

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Figure 16.10 Synthesis of thyroid hormone.

© 2013 Pearson Education, Inc.

Slide 3

Thyroglobulin is synthesized and discharged into the follicle lumen.

1

Golgi

apparatus

Rough

ER

Capillary

Colloid in

lumen of

follicle

Thyroid follicular cells

Tyrosines (part of thyroglobulin

molecule)

Colloid

2

Iodide (I−)

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

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Figure 16.10 Synthesis of thyroid hormone.

© 2013 Pearson Education, Inc.

Slide 4

Thyroglobulin is synthesized and discharged into the follicle lumen.

1

Golgi

apparatus

Rough

ER

Capillary

Colloid in

lumen of

follicle

Thyroid follicular cells

Tyrosines (part of thyroglobulin

molecule)

Colloid

2

Iodide (I−)

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

Iodine

3

Iodide is oxidized to iodine.

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Figure 16.10 Synthesis of thyroid hormone.

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Slide 5

Thyroglobulin is synthesized and discharged into the follicle lumen.

1

Golgi

apparatus

Rough

ER

Capillary

Colloid in

lumen of

follicle

Thyroid follicular cells

Tyrosines (part of thyroglobulin

molecule)

Colloid

2

Iodide (I−)

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

Iodine

3

Iodide is oxidized to iodine.

4

Iodine is attached to tyrosine in colloid, forming DIT and MIT.

Thyro-

globulin

colloid

DIT

MIT

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Figure 16.10 Synthesis of thyroid hormone.

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Slide 6

Thyroglobulin is synthesized and discharged into the follicle lumen.

1

Golgi

apparatus

Rough

ER

Capillary

Colloid in

lumen of

follicle

Thyroid follicular cells

Tyrosines (part of thyroglobulin

molecule)

Colloid

2

Iodide (I−)

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

Iodine

3

Iodide is oxidized to iodine.

4

Iodine is attached to tyrosine in colloid, forming DIT and MIT.

Thyro-

globulin

colloid

DIT

MIT

5

Iodinated tyrosines are linked together to form T3 and T4.

T3

T4

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Figure 16.10 Synthesis of thyroid hormone.

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Slide 7

Thyroglobulin is synthesized and discharged into the follicle lumen.

1

Golgi

apparatus

Rough

ER

Capillary

Colloid in

lumen of

follicle

Thyroid follicular cells

Tyrosines (part of thyroglobulin

molecule)

Colloid

2

Iodide (I−)

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

Iodine

3

Iodide is oxidized to iodine.

4

Iodine is attached to tyrosine in colloid, forming DIT and MIT.

Thyro-

globulin

colloid

DIT

MIT

5

Iodinated tyrosines are linked together to form T3 and T4.

T3

T4

6

Lysosome

Thyroglobulin colloid is endocytosed and combined with a lysosome.

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Transport and Regulation of TH

  • T4 and T3 transported by thyroxine-binding globulins (TBGs)
  • Both bind to target receptors, but T3 is ten times more active than T4
  • Peripheral tissues convert T4 to T3

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Hypothalamus

TRH

Anterior pituitary

TSH

Thyroid gland

Thyroid

hormones

Target cells

Stimulates

Figure 16.8 Regulation of thyroid hormone secretion.

Inhibits

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Homeostatic Imbalances of TH

  • Hyposecretion in adults—myxedema; goiter if due to lack of iodine
  • Hyposecretion in infants—cretinism
  • Hypersecretion—Graves' disease

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Calcitonin

  • Produced by parafollicular (C) cells
  • No known physiological role in humans
  • Antagonist to parathyroid hormone (PTH)
  • At higher than normal doses
    • Inhibits osteoclast activity and release of Ca2+ from bone matrix
    • Stimulates Ca2+ uptake and incorporation into bone matrix

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Parathyroid Glands

  • Four to eight tiny glands embedded in posterior aspect of thyroid
  • Contain oxyphil cells (function unknown) and parathyroid cells that secrete parathyroid hormone (PTH) or parathormone
  • PTH—most important hormone in Ca2+ homeostasis

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Parathyroid Hormone

  • Functions
    • Stimulates osteoclasts to digest bone matrix and release Ca2+ to blood
    • Enhances reabsorption of Ca2+ and secretion of phosphate by kidneys
    • Promotes activation of vitamin D (by kidneys); increases absorption of Ca2+ by intestinal mucosa
  • Negative feedback control: rising Ca2+ in blood inhibits PTH release

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Figure 16.13 Effects of parathyroid hormone on bone, the kidneys, and the intestine.

Osteoclast activity

in bone causes Ca2+

and PO43- release

into blood

Hypocalcemia

(low blood Ca2+)

PTH release from

parathyroid gland

Ca2+ reabsorption

in kidney tubule

Activation of

vitamin D by kidney

Ca2+ absorption

from food in small

intestine

Ca2+ in blood

Initial stimulus

Physiological response

Result

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Homeostatic Imbalances of PTH

  • Hyperparathyroidism due to tumor
    • Bones soften and deform
    • Elevated Ca2+ depresses nervous system and contributes to formation of kidney stones
  • Hypoparathyroidism following gland trauma or removal or dietary magnesium deficiency
    • Results in tetany, respiratory paralysis, and death

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Adrenal (Suprarenal) Glands

  • Paired, pyramid-shaped organs atop kidneys
  • Structurally and functionally are two glands in one
    • Adrenal medulla—nervous tissue; part of sympathetic nervous system
    • Adrenal cortex—three layers of glandular tissue that synthesize and secrete corticosteroids

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Adrenal Cortex

  • Three layers of cortex produce the different corticosteroids
    • Zona glomerulosa—mineralocorticoids
    • Zona fasciculata—glucocorticoids
    • Zona reticularis—gonadocorticoids

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Mineralocorticoids

  • Regulate electrolytes (primarily Na+ and K+) in ECF
    • Importance of Na+: affects ECF volume, blood volume, blood pressure, levels of other ions
    • Importance of K+: sets RMP of cells
  • Aldosterone most potent mineralocorticoid
    • Stimulates Na+ reabsorption and water retention by kidneys; elimination of K+

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Aldosterone

  • Release triggered by
    • Decreasing blood volume and blood pressure
    • Rising blood levels of K+

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Mechanisms of Aldosterone Secretion

  • Renin-angiotensin-aldosterone mechanism: decreased blood pressure stimulates kidneys to release renin 🡪 triggers formation of angiotensin II, a potent stimulator of aldosterone release
  • Plasma concentration of K+: increased K+ directly influences zona glomerulosa cells to release aldosterone
  • ACTH: causes small increases of aldosterone during stress
  • Atrial natriuretic peptide (ANP): blocks renin and aldosterone secretion to decrease blood pressure

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Figure 16.15 Major mechanisms controlling aldosterone release from the adrenal cortex.

Blood volume

and/or blood

pressure

K+ in blood

Stress

Blood pressure

and/or blood

volume

Hypo-

thalamus

Heart

CRH

Anterior

pituitary

Direct

stimulating

effect

Initiates

cascade

that

produces

Renin

Angiotensin II

ACTH

Atrial natriuretic

peptide (ANP)

Inhibitory

effect

Zona glomerulosa

of adrenal cortex

Enhanced

secretion

of aldosterone

Targets

kidney tubules

Absorption of Na+ and

water; increased K+ excretion

Blood volume

and/or blood pressure

Kidney

Primary regulators

Other factors

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Homeostatic Imbalances of Aldosterone

  • Aldosteronism—hypersecretion due to adrenal tumors
    • Hypertension and edema due to excessive Na+
    • Excretion of K+ leading to abnormal function of neurons and muscle

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Glucocorticoids

  • Keep blood glucose levels relatively constant
  • Maintain blood pressure by increasing action of vasoconstrictors
  • Cortisol (hydrocortisone)
    • Only one in significant amounts in humans
  • Cortisone
  • Corticosterone

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Glucocorticoids: Cortisol

  • Released in response to ACTH, patterns of eating and activity, and stress
  • Prime metabolic effect is gluconeogenesis—formation of glucose from fats and proteins
    • Promotes rises in blood glucose, fatty acids, and amino acids
  • "Saves" glucose for brain
  • Enhances vasoconstriction 🡪 rise in blood pressure to quickly distribute nutrients to cells

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Homeostatic Imbalances of Glucocorticoids

  • Hypersecretion—Cushing's syndrome/disease
    • Depresses cartilage and bone formation
    • Inhibits inflammation
    • Depresses immune system
    • Disrupts cardiovascular, neural, and gastrointestinal function
  • Hyposecretion—Addison's disease
    • Also involves deficits in mineralocorticoids
      • Decrease in glucose and Na+ levels
      • Weight loss, severe dehydration, and hypotension

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Figure 16.16 The effects of excess glucocorticoid.

Patient before onset.

Same patient with Cushing’s

syndrome. The white arrow shows

the characteristic “buffalo hump” of

fat on the upper back.

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Gonadocorticoids (Sex Hormones)

  • Most weak androgens (male sex hormones) converted to testosterone in tissue cells, some to estrogens
  • May contribute to
    • Onset of puberty
    • Appearance of secondary sex characteristics
    • Sex drive in women
    • Estrogens in postmenopausal women

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Adrenal Medulla

  • Medullary chromaffin cells synthesize epinephrine (80%) and norepinephrine (20%)
  • Effects
    • Vasoconstriction
    • Increased heart rate
    • Increased blood glucose levels
    • Blood diverted to brain, heart, and skeletal muscle

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Adrenal Medulla

  • Responses brief
  • Epinephrine stimulates metabolic activities, bronchial dilation, and blood flow to skeletal muscles and heart
  • Norepinephrine influences peripheral vasoconstriction and blood pressure

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Figure 16.17 Stress and the adrenal gland.

Short-term stress

Prolonged stress

Nerve impulses

Spinal cord

Preganglionic

sympathetic

fibers

Adrenal medulla

(secretes amino acid–

based hormones)

Catecholamines

(epinephrine and

norepinephrine)

Short-term stress response

Stress

Hypothalamus

Corticotropic cells

of anterior pituitary

To target in blood

CRH (corticotropin-

releasing hormone)

Adrenal cortex

(secretes steroid

hormones)

Mineralocorticoids

Glucocorticoids

ACTH

• Heart rate increases

Long-term stress response

• Kidneys retain

sodium and water

• Proteins and fats converted

to glucose or broken down

for energy

• Blood glucose increases

• Blood pressure increases

• Bronchioles dilate

• Liver converts glycogen to glucose and releases

glucose to blood

• Blood flow changes, reducing digestive system activity

and urine output

• Metabolic rate increases

• Blood volume and

blood pressure

rise

• Immune system

supressed

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Pineal Gland

  • Small gland hanging from roof of third ventricle
  • Pinealocytes secrete melatonin, derived from serotonin
  • Melatonin may affect
    • Timing of sexual maturation and puberty
    • Day/night cycles
    • Physiological processes that show rhythmic variations (body temperature, sleep, appetite)
    • Production of antioxidant and detoxification molecules in cells

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Pancreas

  • Triangular gland partially behind stomach
  • Has both exocrine and endocrine cells
    • Acinar cells (exocrine) produce enzyme-rich juice for digestion
    • Pancreatic islets (islets of Langerhans) contain endocrine cells
      • Alpha (α) cells produce glucagon (hyperglycemic hormone)
      • Beta (β) cells produce insulin (hypoglycemic hormone)

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Figure 16.18 Photomicrograph of differentially stained pancreatic tissue.

Pancreatic islet

• α (Glucagon-

producing)

cells

• β (Insulin-

producing)

cells

Pancreatic acinar

cells (exocrine)

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Glucagon

  • Major target—liver
  • Causes increased blood glucose levels
  • Effects
    • Glycogenolysis—breakdown of glycogen to glucose
    • Gluconeogenesis—synthesis of glucose from lactic acid and noncarbohydrates
    • Release of glucose to blood

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Insulin

  • Effects of insulin
    • Lowers blood glucose levels
    • Enhances membrane transport of glucose into fat and muscle cells
    • Inhibits glycogenolysis and gluconeogenesis
    • Participates in neuronal development and learning and memory
  • Not needed for glucose uptake in liver, kidney or brain

​

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Figure 16.19 Insulin and glucagon from the pancreas regulate blood glucose levels.

Stimulates glucose

uptake by cells

Insulin

Stimulates

glycogen

formationw

Pancreas

Tissue cells

Glucose

Glycogen

Liver

Blood

glucose

falls to

normal

range.

IMBALANCE

Stimulus

Blood

glucose level

BALANCE: Normal blood glucose level (about 90 mg/100 ml)

Pancreas

IMBALANCE

Glucose

Glycogen

Liver

Stimulates

glycogen

breakdown

Blood

glucose

rises to

normal

range.

Stimulus

Blood

glucose level

Glucagon

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Factors That Influence Insulin Release

  • Elevated blood glucose levels – primary stimulus
  • Rising blood levels of amino acids and fatty acids
  • Release of acetylcholine by parasympathetic nerve fibers
  • Hormones glucagon, epinephrine, growth hormone, thyroxine, glucocorticoids
  • Somatostatin; sympathetic nervous system

​

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Homeostatic Imbalances of Insulin

  • Diabetes mellitus (DM)
    • Due to hyposecretion (type 1) or hypoactivity (type 2) of insulin
    • Blood glucose levels remain high 🡪 nausea 🡪 higher blood glucose levels (fight or flight response)
    • Glycosuria – glucose spilled into urine
    • Fats used for cellular fuel 🡪 lipidemia; if severe 🡪 ketones (ketone bodies) from fatty acid metabolism 🡪 ketonuria and ketoacidosis
    • Untreated ketoacidosis 🡪 hyperpnea; disrupted heart activity and O2 transport; depression of nervous system 🡪 coma and death possible

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Diabetes Mellitus: Signs

  • Three cardinal signs of DM
    • Polyuria—huge urine output
      • Glucose acts as osmotic diuretic
    • Polydipsia—excessive thirst
      • From water loss due to polyuria
    • Polyphagia—excessive hunger and food consumption
      • Cells cannot take up glucose; are "starving"

​

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