Download Thyroid Hormone

Gross Anatomy of Thyroid Gland
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
Figure 16.9 The thyroid gland.
Hyoid bone
Thyroid cartilage
Common carotid
artery
Epiglottis
Colloid-filled
follicles
Follicular cells
Superior thyroid
artery
Inferior thyroid
artery
Isthmus of
thyroid gland
Trachea
Left subclavian
artery
Left lateral
lobe of thyroid
gland
Aorta
Parafollicular cells
Gross anatomy of the thyroid gland, anterior view
Photomicrograph of thyroid gland
follicles (145x)
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
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
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
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
Figure 16.10 Synthesis of thyroid hormone.
Slide 1
Thyroid follicular cells
Colloid
1 Thyroglobulin is synthesized and
discharged into the follicle lumen.
Tyrosines (part of thyroglobulin
molecule)
Capillary
4 Iodine is attached to tyrosine
in colloid, forming DIT and MIT.
Golgi
apparatus
Rough
ER
Iodine
3 Iodide
is oxidized
to iodine.
2 Iodide (I–) is trapped
(actively transported in).
Iodide (I−)
T4
T3
Lysosome
DIT
MIT
Thyroglobulin
colloid
5 Iodinated tyrosines are
linked together to form T3
and T4.
T4
T3
T4
T3
To peripheral tissues
6 Thyroglobulin colloid is
endocytosed and combined
with a lysosome.
7 Lysosomal enzymes
cleave T4 and T3 from
thyroglobulin and hormones
diffuse into bloodstream.
Colloid in
lumen of
follicle
Figure 16.10 Synthesis of thyroid hormone.
Slide 2
Thyroid follicular cells
Colloid
1 Thyroglobulin is synthesized and
discharged into the follicle lumen.
Capillary
Tyrosines (part of thyroglobulin
molecule)
Golgi
apparatus
Rough
ER
Colloid in
lumen of
follicle
Figure 16.10 Synthesis of thyroid hormone.
Slide 3
Thyroid follicular cells
Colloid
1 Thyroglobulin is synthesized and
discharged into the follicle lumen.
Capillary
Tyrosines (part of thyroglobulin
molecule)
Golgi
apparatus
Rough
ER
Iodide (I−)
2 Iodide (I–) is trapped
(actively transported in).
Colloid in
lumen of
follicle
Figure 16.10 Synthesis of thyroid hormone.
Slide 4
Thyroid follicular cells
Colloid
1 Thyroglobulin is synthesized and
discharged into the follicle lumen.
Capillary
Tyrosines (part of thyroglobulin
molecule)
Golgi
apparatus
Rough
ER
Iodide (I−)
Iodine
3 Iodide
is oxidized
to iodine.
2 Iodide (I–) is trapped
(actively transported in).
Colloid in
lumen of
follicle
Figure 16.10 Synthesis of thyroid hormone.
Slide 5
Thyroid follicular cells
Colloid
1 Thyroglobulin is synthesized and
discharged into the follicle lumen.
Capillary
Tyrosines (part of thyroglobulin
molecule)
4 Iodine is attached to tyrosine
in colloid, forming DIT and MIT.
Golgi
apparatus
Rough
ER
Iodide (I−)
Iodine
3 Iodide
is oxidized
to iodine.
DIT
MIT
Thyroglobulin
colloid
2 Iodide (I–) is trapped
(actively transported in).
Colloid in
lumen of
follicle
Figure 16.10 Synthesis of thyroid hormone.
Slide 6
Thyroid follicular cells
Colloid
1 Thyroglobulin is synthesized and
discharged into the follicle lumen.
Tyrosines (part of thyroglobulin
molecule)
Capillary
4 Iodine is attached to tyrosine
in colloid, forming DIT and MIT.
Golgi
apparatus
Rough
ER
Iodide (I−)
2 Iodide (I–) is trapped
(actively transported in).
Iodine
3 Iodide
is oxidized
to iodine.
T4
T3
DIT
MIT
Thyroglobulin
colloid
5 Iodinated tyrosines are
linked together to form T3
and T4.
Colloid in
lumen of
follicle
Figure 16.10 Synthesis of thyroid hormone.
Slide 7
Thyroid follicular cells
Colloid
1 Thyroglobulin is synthesized and
discharged into the follicle lumen.
Tyrosines (part of thyroglobulin
molecule)
Capillary
4 Iodine is attached to tyrosine
in colloid, forming DIT and MIT.
Golgi
apparatus
Rough
ER
Iodide (I−)
Iodine
3 Iodide
is oxidized
to iodine.
2 Iodide (I–) is trapped
(actively transported in).
Lysosome
T4
T3
DIT
MIT
Thyroglobulin
colloid
5 Iodinated tyrosines are
linked together to form T3
and T4.
6 Thyroglobulin colloid is
endocytosed and combined
with a lysosome.
Colloid in
lumen of
follicle
Figure 16.10 Synthesis of thyroid hormone.
Slide 8
Thyroid follicular cells
Colloid
1 Thyroglobulin is synthesized and
discharged into the follicle lumen.
Tyrosines (part of thyroglobulin
molecule)
Capillary
4 Iodine is attached to tyrosine
in colloid, forming DIT and MIT.
Golgi
apparatus
Rough
ER
Iodine
3 Iodide
is oxidized
to iodine.
2 Iodide (I–) is trapped
(actively transported in).
Iodide (I−)
T4
T3
Lysosome
DIT
MIT
Thyroglobulin
colloid
5 Iodinated tyrosines are
linked together to form T3
and T4.
T4
T3
T4
T3
To peripheral tissues
6 Thyroglobulin colloid is
endocytosed and combined
with a lysosome.
7 Lysosomal enzymes
cleave T4 and T3 from
thyroglobulin and hormones
diffuse into bloodstream.
Colloid in
lumen of
follicle
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
Transport and Regulation of TH
• Negative feedback regulation of TH
release
– Rising TH levels provide negative feedback
inhibition on release of TSH
– Hypothalamic thyrotropin-releasing hormone
(TRH) can overcome negative feedback
during pregnancy or exposure to cold
Figure 16.8 Regulation of thyroid hormone secretion.
Hypothalamus
TRH
Anterior pituitary
TSH
Thyroid gland
Thyroid
hormones
Target cells
Stimulates
Inhibits
Homeostatic Imbalances of TH
• Hyposecretion in adults—myxedema;
goiter if due to lack of iodine
• Hyposecretion in infants—cretinism
• Hypersecretion—Graves' disease
Figure 16.11 Thyroid disorders.
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
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
Figure 16.12 The parathyroid glands.
Pharynx
(posterior
aspect)
Capillary
Thyroid
gland
Parathyroid
glands
Esophagus
Trachea
Parathyroid
cells
(secrete
parathyroid
hormone)
Oxyphil
cells
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
Figure 16.13 Effects of parathyroid hormone on bone, the kidneys, and the intestine.
Hypocalcemia
(low blood Ca2+)
PTH release from
parathyroid gland
Osteoclast activity
in bone causes Ca2+
and PO43- release
into blood
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
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
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
Adrenal Cortex
• Three layers of cortex produce the
different corticosteroids
– Zona glomerulosa—mineralocorticoids
– Zona fasciculata—glucocorticoids
– Zona reticularis—gonadocorticoids
Figure 16.14 Microscopic structure of the adrenal gland.
Hormones
secreted
Zona
glomerulosa
Aldosterone
Zona
fasciculata
Cortex
Adrenal gland
• Medulla
• Cortex
Capsule
Cortisol
and
androgens
Kidney
Medulla
Zona
reticularis
Adrenal
medulla
Drawing of the histology of the
adrenal cortex and a portion of
the adrenal medulla
Epinephrine
and
norepinephrine
Photomicrograph (115x)
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+
Aldosterone
• Release triggered by
– Decreasing blood volume and blood pressure
– Rising blood levels of K+
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
Figure 16.15 Major mechanisms controlling aldosterone release from the adrenal cortex.
Primary regulators
Blood volume
and/or blood
pressure
K+ in blood
Other factors
Stress
Blood pressure
and/or blood
volume
Hypothalamus
Kidney
Heart
CRH
Renin
Direct
stimulating
effect
Initiates
cascade
that
produces
Anterior
pituitary
Atrial natriuretic
peptide (ANP)
ACTH
Angiotensin II
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
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
Glucocorticoids
• Keep blood glucose levels relatively
constant
• Maintain blood pressure by increasing
action of vasoconstrictors
• Cortisol (hydrocortisone)
– Only one in significant amounts in humans
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
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
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.
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
Gonadocorticoids
• Hypersecretion
– Adrenogenital syndrome (masculinization)
– Not noticeable in adult males
– Females and prepubertal males
• Boys – reproductive organs mature; secondary sex
characteristics emerge early
• Females – beard, masculine pattern of body hair;
clitoris resembles small penis
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
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
Adrenal Medulla
• Hypersecretion
– Hyperglycemia, increased metabolic rate,
rapid heartbeat and palpitations,
hypertension, intense nervousness, sweating
• Hyposecretion
– Not problematic
– Adrenal catecholamines not essential to life
Figure 16.17 Stress and the adrenal gland.
Short-term stress
Prolonged stress
Stress
Nerve impulses
Hypothalamus
CRH (corticotropinreleasing hormone)
Spinal cord
Corticotropic cells
of anterior pituitary
To target in blood
Preganglionic
sympathetic
fibers
Adrenal medulla
(secretes amino acid–
based hormones)
Catecholamines
(epinephrine and
norepinephrine)
Short-term stress response
• Heart rate 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
ACTH
Mineralocorticoids
Adrenal cortex
(secretes steroid
hormones)
Glucocorticoids
Long-term stress response
• Kidneys retain
• Proteins and fats converted
sodium and water
to glucose or broken down
for energy
• Blood volume and
• Blood glucose increases
blood pressure
• Immune system
rise
supressed
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
‘Brain Sand’
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 () cells produce glucagon (hyperglycemic
hormone)
• Beta () cells produce insulin (hypoglycemic
hormone)
Figure 16.18 Photomicrograph of differentially stained pancreatic tissue.
Pancreatic islet
•  (Glucagonproducing)
cells
•  (Insulinproducing)
cells
Pancreatic acinar
cells (exocrine)
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
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
Insulin Action on Cells
• Activates tyrosine kinase enzyme receptor
• Cascade  increased glucose uptake
• Triggers enzymes to
– Catalyze oxidation of glucose for ATP
production – first priority
– Polymerize glucose to form glycogen
– Convert glucose to fat (particularly in adipose
tissue)
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
Figure 16.19 Insulin and glucagon from the pancreas regulate blood glucose levels.
Stimulates glucose
uptake by cells
Tissue cells
Insulin
Stimulates
glycogen
formationw
Pancreas
Glucose
Glycogen
Blood
glucose
falls to
normal
range.
Liver
Stimulus
Blood
glucose level
Stimulus
Blood
glucose level
Blood
glucose
rises to
normal
range.
Pancreas
Glucose
Glycogen
Liver
Stimulates
glycogen
breakdown
Glucagon
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
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"
Homeostatic Imbalances of Insulin
• Hyperinsulinism:
– Excessive insulin secretion
– Causes hypoglycemia
• Low blood glucose levels
• Anxiety, nervousness, disorientation,
unconsciousness, even death
– Treated by sugar ingestion
Table 16.4 Symptoms of Insulin Deficit (Diabetes Mellitus)
Ovaries and Placenta
• Gonads produce steroid sex hormones
– Same as those of adrenal cortex
• Ovaries produce estrogens and progesterone
– Estrogen
• Maturation of reproductive organs
• Appearance of secondary sexual characteristics
• With progesterone, causes breast development and cyclic
changes in uterine mucosa
• Placenta secretes estrogens, progesterone, and
human chorionic gonadotropin (hCG)
Testes
• Testes produce testosterone
– Initiates maturation of male reproductive
organs
– Causes appearance of male secondary
sexual characteristics and sex drive
– Necessary for normal sperm production
– Maintains reproductive organs in functional
state
Other Hormone-producing Structures
• Adipose tissue
– Leptin – appetite control; stimulates
increased energy expenditure
– Resistin – insulin antagonist
– Adiponectin – enhances sensitivity to insulin
Other Hormone-producing Structures
• Enteroendocrine cells of gastrointestinal
tract
– Gastrin stimulates release of HCl
– Secretin stimulates liver and pancreas
– Cholecystokinin stimulates pancreas,
gallbladder, and hepatopancreatic sphincter
– Serotonin acts as paracrine
Other Hormone-producing Structures
• Heart
– Atrial natriuretic peptide (ANP) decreases
blood Na+ concentration, therefore blood
pressure and blood volume
• Kidneys
– Erythropoietin signals production of red
blood cells
– Renin initiates the renin-angiotensinaldosterone mechanism
Other Hormone-producing Structures
• Skeleton (osteoblasts)
– Osteocalcin
• Prods pancreas to secrete more insulin; restricts
fat storage; improves glucose handling; reduces
body fat
• Activated by insulin
• Low levels of osteocalcin in type 2 diabetes –
perhaps increasing levels may be new treatment
• Skin
– Cholecalciferol, precursor of vitamin D
Other Hormone-producing Structures
• Thymus
– Large in infants and children; shrinks as age
– Thymulin, thymopoietins, and thymosins
• May be involved in normal development of T
lymphocytes in immune response
• Classified as hormones; act as paracrines
Developmental Aspects
• Hormone-producing glands arise from all three
germ layers
• Most endocrine organs operate well until old age
• Exposure to pesticides, industrial chemicals,
arsenic, dioxin, and soil and water pollutants
disrupts hormone function
• Sex hormones, thyroid hormone, and
glucocorticoids are vulnerable to the effects of
pollutants
• Interference with glucocorticoids may help
explain high cancer rates in certain areas
Developmental Aspects
• Ovaries undergo significant changes with
age and become unresponsive to
gonadotropins; problems associated with
estrogen deficiency occur
• Testosterone also diminishes with age, but
effect is not usually seen until very old age
Developmental Aspects
• GH levels decline with age - accounts for
muscle atrophy with age
• TH declines with age, contributing to lower
basal metabolic rates
• PTH levels remain fairly constant with age,
but lack of estrogen in older women
makes them more vulnerable to bonedemineralizing effects of PTH