Download Thyroid hormones

Lauralee Sherwood
Hillar Klandorf
Paul Yancey
Chapter 7
Endocrine Systems
Kip McGilliard • Eastern Illinois University
7.1 Introduction: Principles of Endocrinology
 Endocrinology is the study of the evolution
and physiological function of hormones.
• The endocrine system regulates and
coordinates distant organs through the
secretion of hormones.
• Hormones are signal molecules delivered by
circulatory fluids.
• In contrast to the nervous system, the
endocrine system controls activities that
require duration rather than speed.
7.1 Introduction: Principles of Endocrinology
 Chemical classes of hormones
• Peptide and protein hormones
• Chains of amino acids
• Hydrophilic
• Example: Insulin
• Amines
• Derived from tyrosine
• Catecholamines (e.g. epinephrine) are hydrophilic
• Thyroid hormones (e.g. thyroxine) are lipophilic
• Steroids
• Derived from cholesterol
• Lipophilic
• Examples: Testosterone and estradiol
7.1 Introduction: Principles of Endocrinology
 Hormone synthesis and secretion
• Peptide hormones
• Synthesized as large precursor proteins,
preprohormones
• Portions are cleaved and peptide hormone is
packaged into secretory vesicles
• Released from cell by exocytosis
• Steroid hormones
• Cholesterol is synthesized or obtained from diet
• Chemically modified by a series of enzymatic
reactions
• Once synthesized, steroid hormones immediately
diffuse across the plasma membrane
7.1 Introduction: Principles of Endocrinology
Cholesterol
Pregneneolone
17-Hydroxypregneneolone
Progesterone
17-Hydroxyprogesterone
Androstenedione
Estrone
Deoxycortisol
Testosterone
Estradiol
Dehydroepiandrosterone
(adrenal cortex hormone)
(female sex hormone)
11-Deoxycorticosterone
Androgens
(male sex hormones)
Corticosterone
Aldosterone
Mineralocorticoid
(adrenal cortex
hormone)
Cortisol
Estriol
Glucocorticoid
(adrenal cortex
hormone)
Estrogens
(female sex
hormones)
Figure 7-3 p272
7.1 Introduction: Principles of Endocrinology
 Mechanisms of hormone action
• Hormones are widely distributed, but only target cells
have receptors to respond to each hormone
• Peptides and catecholamines bind with membrane
receptors
• Alter the conformation of adjacent ion channels, or
• Activate second-messenger systems
• Steroid and thyroid hormones pass through the
plasma membrane and bind with internal receptors
• Receptors inside the cell are transcription factors that
regulate specific genes
• Hormone receptor complex binds with hormone
response element (HRE) on nuclear DNA
• Turns on synthesis of a specific protein
7.1 Introduction: Principles of Endocrinology
Blood vessel
Plasma
protein
carrier
Steroid
hormone
ECF
Plasma
membrane
Cytoplasm
Cellular response
1 Free lipophilic hormone
9 New protein
brings about
desired response.
diffuses though plasma
membrane
Steroid
hormone
receptor
New
protein
Portion
that binds
hormone
8 New protein
is released from
ribosome and
processed into
final folded form.
Portion
that binds
to DNA
2 Hormone binds with
7 Ribosomes
“read” mRNA
to synthesize
new proteins.
intracellular receptor
specific for it.
DNA-binding
site (active)
6 New
mRNA
leaves
nucleus.
3 Hormone receptor
complex binds with
DNA’s hormone
response element.
mRNA
4 Binding
activates gene.
5 Activated
gene
transcribes
mRNA.
DNA
Nucleus
Hormone Gene
response
element
Figure 7-4 p274
7.1 Introduction: Principles of Endocrinology
 Regulation of plasma concentration of hormones
• Negative feedback control
• When plasma hormone levels fall, hormone
secretion is stimulated
• Neuroendocrine reflexes
• Produce a sudden increase in hormone secretion in
response to a specific stimulus
• Biological rhythms
• Secretion of most hormones rhythmically fluctuates
as a function of time (biological clocks)
• Readjustment of set point by CNS
• Example: Cortisol secretion rises at night to peak
in early morning (diurnal rhythm)
7.1 Introduction: Principles of Endocrinology
7.1 Introduction: Principles of Endocrinology
 Endocrine disorders
• Hyposecretion -- inadequate secretion of a hormone
• Primary hyposecretion -- abnormality within the gland
• Secondary hyposecretion -- deficiency of tropic
hormones
• Hypersecretion -- excessive secretion of a hormone
• Primary or secondary
• Endocrine-disrupting chemicals (EDCs)
• Human-made substances released into the environment
that mimic or oppose the actions of hormones
• Example: DDE and DDT act as anti-androgens in
mammals
7.2 Nonvertebrate Endocrinology
 Growth and molting in insects
• Ecdysone is secreted by the prothoracic glands
• Secretion of ecdysone is stimulated by
prothoracotropic hormone (PTTH) secreted by
neurosecretory cells in brain
• Ecdysone initiates the molting process
• Juvenile hormone (JH) is secreted by the
corpora allata
• JH assures that larval characteristics are retained
• JH levels progressively decline at each larval stage
• Ecdysone in the absence of JH enables
metamorphosis to the adult form
7.2 Nonvertebrate Endocrinology
Stimuli
(related to feeding activities)
anterior end of larva
Hormone
secretory cells
in brain
Juvenile
hormone
Brain
hormone
Prothoracic
gland
Corpus
allatum
β
α–
ecdysone ecdysone
1
2
3
4
Changing blood concentrations of hormones
Larval stages
Pupa
Adult
Figure 7-7 p280
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
Pineal
Hypothalamus
Pituitary
Parathyroid
Thyroid
Thymus
Heart
Stomach
Adrenal gland
Pancreas
Duodenum
Kidney
Skin
Ovaries in
female
Placenta in
pregnant
female
Testes
in male
Figure 7-1 p269
ANIMATION: Major human endocrine
glands
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7.3 Vertebrate Endocrinology:
Central Endocrine Glands
 Pineal gland
• Secretes melatonin
• Maintains circadian rhythms
• Melatonin secretion increases up to 10-fold in
darkness
• Seasonal changes in melatonin secretion
patterns trigger reproduction
• In mammals melatonin output is controlled by
the suprachiasmatic nucleus (SCN) of the
hypothalamus
• SCN receives light information from the eyes
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
Pineal
gland
Photoperiod
Retina
Anestrous
Breeding
Melatonin
SCN
Kisspeptin
neuron
GnRH
Pituitary
LH pulse
Frequency
Follicle
Estradiol
feedback
Ovary
Figure 7-8 p282
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
 Pituitary gland (hypophysis)
• Located at the base of the brain, connected to the
hypothalamus by a thin stalk, the infundibulum
• Posterior pituitary (neurohypophysis)
• Nervous tissue
• Anterior pituitary (adenohypophysis)
• Glandular epithelial tissue
• Intermediate lobe (pars intermedia)
• Absent in birds and cetaceans
• Rudimentary in humans after birth
• Size of intermediate lobe correlates with ability of
animal to adapt to coloration of its environment
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
Hypothalamus
Bone
Anterior
lobe of
pituitary
Posterior
lobe of
pituitary
(a) Relation of pituitary gland to hypothalamus
and rest of brain
Figure 7-9a p285
Hypothalamus
Optic
chiasm
Anterior
pituitary
Connecting stalk
Posterior
pituitary
(b) Enlargement of pituitary gland and its
connection to hypothalamus
Figure 7-9b p285
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
 Intermediate lobe
• Secretes melanocyte-stimulating hormone (MSH)
• α-MSH controls skin coloration via dispersion of
storage granules containing melanin
• In lower vertebrates, α-MSH is opposed by melaninconcentrating hormone (MCH)
• Melanocortin-1 receptor (MC1R) determines skin
color, pelage and feather pigmentation in animals
lacking pars intermedia
• Excessive MSH secretion darkens human skin
• MSH reduces appetite and suppresses immune system
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
 Posterior pituitary
• Connects to the hypothalamus by a neural
pathway
• Neurosecretory neurons have cell bodies in
supraoptic and paraventricular nuclei of
hypothalamus
• Axons terminate on capillaries in posterior pituitary
• Secretes vasopressin and oxytocin
• Evolutionary precursor, arginine vasotocin,
is found in many vertebrates
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
 Posterior pituitary hormones
• Vasopressin
• Enhances retention of water by kidneys
(antidiuretic effect)
• Causes contraction of arteriolar smooth muscle
(vasoconstriction)
• Oxytocin
• Social bonding
• Contraction of uterine smooth muscle
• Ejection of milk from mammary glands
• Arginine vasotocin
• Involved in osmoregulation
• Vasoconstriction
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
Supraoptic
nucleus
1
Neurosecretory
neuronal cell bodies
in hypothalamus
(produce vasopressin
and oxytocin)
Hypothalamus
Paraventricular nucleus
Axons
Hypothalamic posteriorpituitary stalk
Capillary
Anterior
pituitary
Posterior pituitary
Systemic
arterial blood in
Vasopressin
Neuronal terminals in
posterior pituitary
(release vasopressin
and oxytocin into
systemic blood)
Systemic
venous blood
out
Oxytocin
Figure 7-10 p286
Vasopressin
Nephrons
in kidneys
Increases
permeability
of distal and
collecting
tubules to H2O
Arterioles
throughout
body
Causes
vasoconstriction
Oxytocin
Uterus
Stimulates
uterine
contractions
Mammary
glands
Stimulates
milk ejection
during breastfeeding
Figure 7-10 p286
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
 Anterior pituitary hormones
• Growth hormone (GH, somatotropin)
• Stimulates growth and affects metabolism
• Thyroid-stimulating hormone (TSH, thyrotropin)
• Stimulates thyroid hormone secretion by thyroid gland
• Adrenocorticotropic hormone (ACTH, corticotropin)
• Stimulates cortisol secretion by the adrenal cortex
• Follicle-stimulating hormone (FSH)
• Regulates gamete production
• Luteinizing hormone (LH)
• Regulates sex hormone secretion
• Ovulation and formation of corpus luteum in females
• Prolactin (PRL)
• Stimulates milk production by mammary glands
• Wide range of additional actions
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
Hypothalamus
Anterior pituitary
Posterior pituitary
TSH
ACTH
Thyroid
gland
Prolactin
Adrenal
cortex
Thyroid
hormone
(T3 and T4)
Mammary
glands
Breast
growth and
milk
secretion
Cortisol
Increased
metabolic rate
Metabolic actions;
stress response
Growth hormone
Adipose tissue,
muscle, liver
Liver
IGF-I
Bone
(ovaries in
females)
Soft tissues
Growth
LH
Metabolic
actions
FSH
Gonads
Sex hormone
secretion
(estrogen and
progesterone in
females,
testosterone in
(testes
in males)
Gamete production
(ova in females,
sperm in males)
Figure 7-11 p287
ANIMATION: Anterior pituitary function
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7.3 Vertebrate Endocrinology:
Central Endocrine Glands
 Hypothalamic releasing and inhibiting hormones
• Secretion of each anterior pituitary hormone is
regulated by hypothalamic hypophysiotropic
hormones
• Thyrotropin-releasing hormone (TRH)
• Corticotropin-releasing hormone (CRH)
• Gonadotropin-releasing hormone (GnRH)
stimulates release of FSH and LH
• Growth hormone-releasing hormone (GHRH)
• Growth hormone-inhibiting hormone (GHIH,
somatostatin)
• Prolactin-releasing hormone (PRH)
• Prolactin-inhibiting hormone (PIH)
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
 Hypothalamic releasing and inhibiting hormones
• Releasing and inhibiting hormones reach the anterior
pituitary through the hypothalamic-hypophyseal
portal system
• Regulation of hypophysiotropic hormone secretion
• Neural input (e.g. CRH secretion in response to stress)
• Negative-feedback effects of anterior pituitary or target
gland hormones (e.g. cortisol levels above a set point
inhibit CRH and ACTH secretion)
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
Neurosecretory neurons
in hypothalamus (secrete
releasing and inhibiting
hormones into portal system)
Hypothalamus
1
Capillaries in
hypothalamus
Systemic
arterial
blood in
Endocrine cells of
anterior pituitary
(secrete anterior
pituitary hormones
into systemic blood)
1
2
Hypothalamichypophyseal
portal system
3
Posterior
pituitary
4
Capillaries in
anterior pituitary
Systemic
venous
blood out
Releasing
and inhibiting
hormones
5
6
Anterior
pituitary
KEY
= Hypophysiotropic hormones
= Anterior pituitary hormone
Figure 7-13 p289
7.3 Vertebrate Endocrinology:
Central Endocrine Glands
7.4 Endocrine Control of Growth and Development
in Vertebrates
 Growth depends on:
• Adequate diet
• Malnourished animals do not reach full growth
potential
• Seasonally shortened day length reduces growth
by reducing food intake
• Freedom from chronic disease and stressful
environmental conditions
• Glucocorticoids secreted during stress inhibit
growth
• Growth-influencing hormones
• Placental hormones promote fetal growth
• Growth hormone and other hormones promote
growth after birth
7.4 Endocrine Control of Growth and Development
in Vertebrates
 Direct effects of growth hormone (GH)
• Metabolic effects
• Target organs are adipose tissue, skeletal muscles
and liver
• Mobilizes fat stores as a major energy source
• Conserves glucose for use by the brain
• Decreases glucose uptake by muscles and
increases glucose output by the liver
• Enhances immune system
 GH’s growth-promoting actions are mediated by
insulin-like growth factors (IGFs)
7.4 Endocrine Control of Growth and Development
in Vertebrates
 GH/IGF’s growth promoting effects
• Growth of soft tissues
•
•
•
•
Increases number of cells (hyperplasia)
Increases size of cells (hypertrophy)
Promotes uptake of amino acids into cells
Stimulates protein synthesis and inhibits protein
degradation
• Growth of bone
• Promotes increases in bone thickness and length
• Thickness depends on addition of new bone by
osteoblasts
• Length depends on proliferation of cartilage cells
(chondrocytes) in epiphyseal plates and invasion
by osteoblasts
7.4 Endocrine Control of Growth and Development
in Vertebrates
Articular
cartilage
Bone of epiphysis
Epiphyseal plate
Bone of diaphysis
Marrow cavity
(a) Anatomy of a long bone
Figure 7-14a p294
Bone of epiphysis
Diaphysis
Resting
chondrocytes
Epiphyseal plate
Bone of
epiphysis
Chondrocytes
1 undergo cell
Causes
division.
thickening of
epiphyseal
The 2 older
chondrocytes plate
grow larger.
As the extracellular matrix
calcifies, the entrapped
chondrocytes die.
The dead chondrocytes are
cleared away by osteoclasts.
Osteoblasts swarm up from
diaphysis and deposit bone
over persisting remnants of
disintegrating cartilage.
(b) Two sections of the same epiphyseal plate at different times,
depicting the lengthening of long bones
Figure 7-14b p294
7.4 Endocrine Control of Growth and Development
in Vertebrates
 Regulation of growth hormone secretion
• Negative feedback loop involving hypothalamuspituitary-liver axis
• IGF-I inhibits secretion of GH by somatotropes in
anterior pituitary
• IGF-I inhibits GHRH-secreting cells and stimulates
somatostatin-secreting cells in hypothalamus
• Other stimuli to GH secretion
•
•
•
•
Onset of sleep
Exercise, stress, and hypoglycemia
High protein meal
Ghrelin
7.4 Endocrine Control of Growth and Development
in Vertebrates
Bone of epiphysis
Diaphysis
Resting
chondrocytes
Epiphyseal plate
Bone of
epiphysis
Chondrocytes
1 undergo cell
Causes
division.
thickening of
epiphyseal
The 2 older
chondrocytes plate
grow larger.
As the extracellular matrix
calcifies, the entrapped
chondrocytes die.
The dead chondrocytes are
cleared away by osteoclasts.
Osteoblasts swarm up from
diaphysis and deposit bone
over persisting remnants of
disintegrating cartilage.
(b) Two sections of the same epiphyseal plate at different times,
depicting the lengthening of long bones
Figure 7-14b p294
7.4 Endocrine Control of Growth and Development
in Vertebrates
 Growth hormone administration
• Increases bone growth
• Treatment of dwarfism in humans
• Increases muscle mass
• Abuse by athletes
• Improved meat production in swine
• Increases milk production in dairy cattle
7.5 Thyroid Gland
 Thyroid gland is located in the throat below
the larynx
• Composed of follicular cells arranged in fluidfilled spheres (thyroid follicles)
• Colloid serves as an extracellular storage
site for thyroid hormones in the form of
thyroglobulin, a large glycoprotein
7.5 Thyroid Gland
Thyroid
gland
Right lobe Trachea Isthmus Left lobe
(a) Gross anatomy of thyroid gland
Figure 7-16a p298
Follicular cell
Colloid
C cell
(b) Light-microscopic appearance of thyroid gland
Figure 7-16b p298
7.5 Thyroid Gland

Thyroid hormone synthesis
1.
Thyroglobulin (Tg) is synthesized by thyroid
follicular cells (incorporating tyrosine) and secreted
into colloid by exocytosis
2. Thyroid follicular cells efficiently capture iodide (I-),
obtained from the diet, using an iodide pump
3. Iodide is activated and attached to tyrosine
molecules on Tg in colloid
•
•
Monoiodotyrosine (MIT) has one iodine
Diiodotyrosine (DIT) has two iodines
4. Iodinated tyrosines couple to form
tetraiodothyronine (T4, thyroxine) and
triiodothyronine (T3)
7.5 Thyroid Gland

Secretion of thyroid hormones
1. Follicular cells take up a piece of colloid (containing
iodinated Tg) by phagocytosis
2. Lysosomal enzymes split off T4, T3, MIT and DIT in
the process of breaking down Tg
3. T4 and T3 (biologically active thyroid hormones)
diffuse across follicular cell membrane into
blood, while MIT and DIT are recycled to iodide and
tyrosine
7.5 Thyroid Gland
Thyroid
follicular cell
Blood
Colloid
Endoplasmic
reticulum
2
I–
Golgi
complex
Tg
MIT
Lysosome
DIT 7
T3
T4
MIT
DIT
T3
T4
4b
I–
3
MIT
DIT
T3
T4
DIT
I–
I–
8b MIT
8a
Tg
4a
I–
T3 T4
1
5a
6
5b
2 DITs
1 MIT + 1 DIT
T3
T4
Thyroid
follicle
Figure 7-17 p299
7.5 Thyroid Gland
 Mechanism of thyroid hormone action
• T3 is the major biologically active form of
thyroid hormone
• Most secreted T4 is activated by conversion
to T3 by a deiodinase enzyme
• T3 binds with nuclear receptors attached to
thyroid-response elements of DNA
• Alters transcription of specific mRNAs and
synthesis of specific proteins
7.5 Thyroid Gland
 Effects of thyroid hormones
• Increase basal metabolic rate (BMR) through
increased mitochondrial and Na+-K+ pump activity
• Modulate synthesis and degradation of metabolic fuel
molecules
• Molting in birds and mammals
• Sympathomimetic effect -- increase target cell
•
•
•
•
responsiveness to catecholamines
Increase heart rate and force of contraction
Essential for growth (permissive effect on GH)
Development of CNS
Metamorphosis in amphibians
7.5 Thyroid Gland
Hypothalamus
Thyroid gland
TRH
TSH
Anterior pituitary
Conversion of
thyroxine (+ GH)
into triiodothyronine
(a)
1 day
8 days 21 days 27 days
30 days
40 days
(b)
Figure 7-18 p302
7.5 Thyroid Gland
 Regulation of thyroid hormone secretion
• Negative feedback loop involving
hypothalamus-pituitary-thyroid axis
• Thyroid-stimulating hormone (TSH) stimulates
almost every step of thyroid hormone synthesis and
secretion
• Hypothalamic thyrotropin-releasing hormone
(TRH) stimulates TSH secretion by thyrotropes in
anterior pituitary
• Elevated T3 and T4 levels inhibit TSH secretion
• Other factors affecting thyroid hormone secretion
• Stress inhibits TSH secretion
• Cold stimulates TSH secretion (infants)
7.5 Thyroid Gland
Stress
Cold in
infants
Hypothalamus
Thyrotropin-releasing
hormone (TRH)
Anterior pituitary
Thyroid-stimulating
hormone (TSH)
Thyroid gland
Thyroid hormone
(T3 and T4)
Metabolic rate and heat production;
enhancement of growth and CNS development;
enhancement of sympathetic activity
Figure 7-19 p303
7.5 Thyroid Gland
 Abnormalities of thyroid function
• Hypothyroidism -- low thyroid activity
• Causes
• Primary failure of thyroid gland or
• Secondary to a deficiency of TSH (or TRH) or
• Inadequate dietary supply of iodine
• Symptoms stem from reduced metabolic activity
(e.g. weight gain, fatigue, poor tolerance of cold)
• Hyperthyroidism -- elevated thyroid activity
• Symptoms stem from increased metabolic activity
(e.g. weight loss, increased heart rate, anxiety)
7.6 Adrenal Glands
 Adrenal glands are located above the kidneys
• Outer adrenal cortex is composed of
steroidogenic cells of mesodermal origin
• Inner adrenal medulla is composed of
chromaffin cells of neural crest origin
• Steroidogenic and chromaffin tissues are
intermingled in most non-mammalian species
7.6 Adrenal Glands
 Steroid hormones of the adrenal cortex
• Derived from cholesterol
• Modified by stepwise enzymatic reactions
• Mineralocorticoids (e.g. aldosterone)
• Influence mineral (electrolyte) balance
• Produced in zona glomerulosa
• Glucocorticoids (e.g. cortisol)
• Role in metabolism of glucose, proteins and lipids
• Produced in zona fasciculata
• Sex steroids (e.g. dehydroepiandrosterone)
• Androgenic (masculinizing) effects
• Produced in zona fasciculata and zona reticularis
7.6 Adrenal Glands
Adrenal
cortex
Adrenal medulla
Adrenal gland
Kidney
(a) Location and gross structure of adrenal glands
Figure 7-20a p305
Mineralcorticoids
Connective tissue
capsule
Zona
glomerulosa
Zona
fasciculata
Cortex
Glucocorticoids
(sex hormones)
Zona
reticularis
Medulla
Catecholamines
(b) Layers of adrenal cortex
Figure 7-20b p305
7.6 Adrenal Glands
Cholesterol
Pregneneolone
17-Hydroxypregneneolone
Progesterone
17-Hydroxyprogesterone
Androstenedione
Estrone
Deoxycortisol
Testosterone
Estradiol
Dehydroepiandrosterone
(adrenal cortex hormone)
(female sex hormone)
11-Deoxycorticosterone
Androgens
(male sex hormones)
Corticosterone
Aldosterone
Mineralocorticoid
(adrenal cortex
hormone)
Cortisol
Estriol
Glucocorticoid
(adrenal cortex
hormone)
Estrogens
(female sex
hormones)
Figure 7-3 p272
7.6 Adrenal Glands
 Effects of glucocorticoids
• Metabolic effects -- increase blood glucose,
while reducing protein and fat stores
• Permissive actions (e.g. permit catecholamines
to induce vasoconstriction)
• Enhanced memory
• Adaptation to long-term stress
• Anti-inflammatory and immunosuppressive
effects, especially at high doses
7.6 Adrenal Glands
 Regulation of glucocorticoid secretion
• Negative feedback loop involving
hypothalamus-pituitary-adrenal axis
• Adrenocorticotropic hormone (ACTH) stimulates
cortisol secretion
• Hypothalamic corticotropin-releasing hormone
(CRH) stimulates ACTH secretion by corticotropes
in the anterior pituitary
• Elevated glucocorticoid levels inhibit CRH and
ACTH secretion
• Other factors affecting glucocorticoid secretion
• Stress stimulates CRH secretion
• Circadian rhythm
7.6 Adrenal Glands
Stress
Diurnal rhythm
Hypothalamus
Corticotropin-releasing
hormone (CRH)
Anterior pituitary
Adrenocorticotropic
hormone (ACTH)
Adrenal cortex
Cortisol
Metabolic fuels
and building blocks
available to help
resist stress
Blood glucose
(by stimulating
gluconeogenesis
and inhibiting glucose uptake)
Blood amino acids
(by stimulating protein
degradation)
Blood fatty acids
(by stimulating lipolysis)
Figure 7-21 p307
7.6 Adrenal Glands
 Abnormalities of adrenocortical function
• Cushing’s syndrome -- excessive cortisol secretion
• Most common cause -- overstimulation by excess ACTH
• Consequences of excessive gluconeogenesis
• High blood glucose and protein loss
• Redistribution of fat in humans and dogs
• Addison’s disease (primary adrenocortical
insufficiency) -- deficiency of adrenal steroids
• Most common cause -- autoimmune destruction of the
adrenal cortex
• Aldosterone deficiency can be fatal
• Cortisol deficiency causes poor response to stress,
hypoglycemia, and lack of permissive actions
7.6 Adrenal Glands
 Chromaffin cells in the adrenal medulla are
modified postganglionic sympathetic neurons.
• Secrete norepinephrine (NE) and epinephrine
(ratio varies between species)
• Both are catecholamines derived from tyrosine
• Most synthetic steps take place in cytoplasm
• Stored in chromaffin granules
• Secretion is by exocytosis (similar to
neurotransmitter secretion)
• Secretion is stimulated by the sympathetic
system (e.g. during fear or stress)
7.6 Adrenal Glands
 Effects of adrenal catecholamines
• Increased cardiac output and arterial blood
pressure
• Vasodilation of coronary and skeletal-muscle
arterioles
• Dilation of respiratory airways
• Inhibition of digestive activity
• Mobilization of stored carbohydrates and fat
• CNS arousal
• Sweating
• Dilation of pupils and flattening of lens
7.6 Adrenal Glands
 Multifaceted stress response is
coordinated by the hypothalamus
• Hypothalamus receives input concerning
physical and emotional stressors
• Activates sympathetic nervous system
• Secretes CRH
• Secretes vasopressin
• Chronic stress responses are detrimental
• Breakdown of body structures
• Reproductive failure
• Increased susceptibility to disease
7.6 Adrenal Glands
7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
 Metabolism refers to all chemical
reactions that occur within body cells.
• Anabolism -- synthesis of larger organic
molecules from smaller subunits
• Requires energy in the form of ATP
• Manufacture of molecules needed by the cell
• Storage of nutrients
• Catabolism -- breakdown of organic
molecules into smaller subunits
• Hydrolysis of large organic macromolecules
• Oxidation of smaller molecules (e.g. glucose)
to release energy for ATP production
7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
 Regulation of metabolic fuels
• Dietary intake is usually intermittent
• Absorptive state
• After a meal
• Glucose is plentiful and used as the major energy
source
• Excess nutrients are stored as glycogen or
triglycerides
• Postabsorptive state
• Between meals (fasting)
• Endogenous energy stores are mobilized to provide
energy
• Fatty acids are the major energy source for most
tissues
7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
 Pancreas is composed of both exocrine and
endocrine tissues
• Exocrine portion secretes digestive enzymes through
the pancreatic duct into the digestive tract lumen
• Islets of Langerhans are integrators of endocrine
regulatory responses and secrete hormones
• Pancreatic hormones are the dominant hormonal
regulators of glucose homeostasis
•
•
•
•
β cells secrete insulin
α cells secrete glucagon
D cells secrete somatostatin
F cells secrete pancreatic polypeptide
7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
 Effects of insulin
• Lowers blood glucose and promotes storage of
carbohydrates
•
•
•
•
Facilitates glucose transport into most cells
Stimulates glycogenesis in skeletal muscle and liver
Inhibits glycogenolysis in liver
Inhibits gluconeogenesis in liver
• Lowers blood fatty acids and promotes storage of
triglycerides
• Stimulates production of fatty acids from glucose
• Inhibits lipolysis
• Lowers blood amino acids and enhances protein
synthesis
• Promotes uptake of amino acids into cells
7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
Factors that increase blood glucose
Factors that decrease blood glucose
Transport of glucose into cells:
––For utilization for energy production
––For storage
*as glycogen through glycogenesis
*as triglycerides
Glucose absorption from
digestive tract
Blood
glucose
Hepatic glucose production:
––Through glycogenolysis
of stored glycogen
––Through gluconeogenesis
Urinary excretion of glucose
(occurs only abnormally, when
blood glucose level becomes so
high it exceeds the reabsorptive
capacity of kidney tubules during
urine formation)
Figure 7-24 p317
ANIMATION: Hormones and glucose
metabolism
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7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
 Regulation of insulin secretion
• Direct negative-feedback system between
pancreatic β cells and the blood glucose level
• During absorption of a meal, insulin secretion
increases
• Other factors that stimulate insulin secretion:
• Increased blood amino acids
• Gastrointestinal hormones -- glucoseindependent insulinotropic peptide (GIP),
glucagon-like peptide (GLP)
• Increased parasympathetic activity
7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
Gastrointestinal
hormones (incretins)
Blood glucose
concentration
Blood amino acid
concentration
Major control
Food intake
Parasympathetic
stimulation
Islet
cells
Sympathetic stimulation
(and epinephrine)
Insulin secretion
Blood glucose
Blood fatty acids
Blood amino acids
Protein synthesis
Fuel storage
Figure 7-25 p319
7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
 Glucagon
• Effects oppose those of insulin
• Increases hepatic glucose production and raises
blood glucose levels
• Promotes fat breakdown and inhibits triglyceride
synthesis, raising fatty acid levels in blood
• Promotes protein breakdown in liver, but does not
affect muscle protein
• Glucagon secretion is increased during the
postabsorptive state when blood glucose
levels are low
7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
Blood glucose
β cell
α cell
Glucagon
Insulin
Blood glucose
to normal
Blood glucose
α cell
β cell
Glucagon
Insulin
Blood glucose
to normal
Figure 7-26 p321
Blood glucose
Blood glucose
a cell
b cell
a cell
b cell
Glucagon
Insulin
Glucagon
Insulin
Blood glucose
to normal
Blood glucose
to normal
Stepped Art
Figure 7-26 p321
7.7 Endocrine Control of Fuel Metabolism
in Vertebrates
 Diabetes mellitus
• Elevated blood glucose levels (hyperglycemia)
• Glucose in the urine attracts water to cause
excessive urination
• Type I (insulin-dependent) diabetes mellitus
• Lack of insulin secretion by pancreatic β cells
• Requires administration of insulin
• Type II (non-insulin-dependent) diabetes mellitus
• Insulin levels are normal or elevated
• Reduced sensitivity of target cells to insulin
7.8 Endocrine Control of Calcium Metabolism
in Vertebrates
 Importance of calcium
• In mammals, 99% of calcium (Ca2+) is stored in the
skeleton and teeth
• Only free Ca2+ in plasma is biologically active and
subject to regulation
• Both Ca2+ homeostasis and Ca2+ balance must be
regulated
• Ca2+ plays a vital role in:
• Neuromuscular excitability
• Excitation-contraction coupling in cardiac and smooth
muscle
• Stimulus-secretion coupling
• Maintenance of tight junctions between cells
• Clotting of blood
7.8 Endocrine Control of Calcium Metabolism
in Vertebrates
 Parathyroid hormone (PTH)
• Secreted by the parathyroid glands, located near the
thyroid gland
• Essential for life
• Raises plasma Ca2+ levels
•
•
•
•
Promotes transfer of Ca2+ from bone fluid into plasma
Promotes resorption of bone by osteoclasts
Increases reabsorption of Ca2+ in the kidneys
Indirectly increases Ca2+ absorption from the small
intestine by activating vitamin D
• PTH secretion is increased in response to a fall in
plasma Ca2+ levels
7.8 Endocrine Control of Calcium Metabolism
in Vertebrates
Osteoblast
Osteocyte
Osteocytic–
osteoblastic
bone
membrane
Osteoblast
Osteoclast
Mineralized
bone
Outer
surface
Blood vessel
Central canal
Canaliculi
Bone fluid
Lamellae
(a) Osteocytic–osteoblastic bone membrane
Figure 7-30a p328
In canaliculi
Mineralized bone:
stable pool of Ca2+
In central canal
Bone fluid:
labile pool
of Ca2+
Fast exchange
1
2
Slow exchange
(Bone
dissolution)
Plasma
Ca2+
Ca2+
Osteocytic–osteoblastic bone membrane
(formed by filmy cytoplasmic extensions of
interconnected osteocytes and osteoblasts)
(b) Fast and slow exchange of Ca2+ between bone and plasma
Figure 7-30b p328
7.8 Endocrine Control of Calcium Metabolism
in Vertebrates
Plasma Ca2+
Plasma Ca2+
Parathyroid glands
Thyroid C cells
PTH
Plasma Ca2+
Calcitonin
Plasma Ca2+
Figure 7-31 p328
7.8 Endocrine Control of Calcium Metabolism
in Vertebrates
 Calcitonin
• Produced by C cells of the mammalian thyroid
gland, ultimobranchial glands in birds, and
connective tissue sheets around the heart in fishes
• Decreases plasma Ca2+ levels
• Decreases transfer of Ca2+ from bone fluid into plasma
• Decreases bone resorption by inhibiting activity of
osteoclasts
• Ability to lower blood Ca2+ is especially important in
marine fishes because of Ca2+ in sea water
• Calcitonin secretion is increased in response to an
increase in plasma Ca2+ levels
7.8 Endocrine Control of Calcium Metabolism
in Vertebrates
 Vitamin D (cholecalciferol)
• Produced in skin from 7-dehydrocholesterol
on exposure to sunlight
• Can also be obtained in the diet
• Activated by sequential alterations in the liver
and kidneys, forming 1,25-(OH)2-vitamin D3
(calcitriol)
• Promotes Ca2+ absorption in the intestine
• Increases sensitivity of bone to PTH
7.8 Endocrine Control of Calcium Metabolism
in Vertebrates
Precursor in skin (7dehydrocholesterol)
Dietary vitamin D
Sunlight
Vitamin D3
Hydroxyl group (OH)
Liver enzymes
25-OH-vitamin D3
Hydroxyl group
PTH
Plasma Ca2+
Kidney enzymes
Plasma PO43 −
1,25-(OH)2 -vitamin D3
(active vitamin D)
Promotes intestinal
absorption of Ca2+ and
PO43 −
Figure 7-32 p329
7.8 Endocrine Control of Calcium Metabolism
in Vertebrates
Relieves
Plasma Ca2+
Parathyroid
glands
PTH
Kidneys
Enhances
responsiveness
of bone to PTH
Renal tubular
Ca2+ reabsorption
Activation
of vitamin D
Bone
Mobilization of
Ca2+ from bone
Intestine
Urinary excretion
of Ca2+
Absorption of
Ca2+ in
intestine
Plasma Ca2+
Figure 7-33 p330
7.8 Endocrine Control of Calcium Metabolism
in Vertebrates
 Disorders of Ca2+ metabolism
• Hyperparathyroidism -- excess PTH
secretion
• “Bones, stones, and abdominal groans”
• Vitamin D deficiency
• Impaired intestinal absorption of Ca2+
• Demineralized bone is soft and deformed
• Rickets in children; osteomalacia in adults
• Excessive demands for Ca2+
• Parturient paresis (milk fever) in dairy cattle
• Egg laying in birds