The Endocrine System

Part B
 Thyroid Gland
 Location:
 Located in the anterior neck, in front of
trachea
 Shape ,Size & weight:
 H or Butterfly shaped,Consisting of two
lateral lobes connected by a median tissue
mass called the isthmus
 The largest pure endocrine gland, 12-15mm
in Height
 Weight 15-20g
 Histology
 Internally, the gland is composed of hollow,
spherical follicles or Acini (50-500µm in
diameter)
 The follicle walls are formed by cuboidal or
 Thyroid Gland
 Lumen of the follicle stores colloid,
consisting of thyroglobulin + iodine
 Thyroid hormone is derived from this
iodinated thyroglobulin
 T4 (93%) and T3 (7%)
 When the gland is inactive, the colloid is
abundant, the follicles are large, and the
cells lining them are flat.
 When the gland is active, the follicles are
small, the cells are cuboid or columnar
 The parafollicular cells (C-cells)
 Don’t reach the lumen
 Lie in the follicular epithelium and protrude
Thyroid Gland Anatomy
Thyroid Gland
Thyroid Hormone
 Thyroid hormone – the body’s major
metabolic hormone
 Consists of two closely related iodine-
containing compounds
 T4 – thyroxine; has two tyrosine
molecules plus four bound iodine atoms
 T3 – triiodothyronine; has two tyrosines
with three bound iodine atoms
T3 and T4 Structures

T 4 or Thyroxine T 3 or Triiodothyronine
 Synthesis of Thyroid Hormone
 Each step in the synthesis is stimulated by
TSH.
 Formation and storage of thyroglobulin
 Ribosomes Thyroglobin  Glogi  Glycated &
paceked in vesicles  discharged in follicle lumen
 Iodide trapping: (Na+/I- symporter) (30 times
more conc.)
 Iodides (I–) are actively taken into the cell, oxidized to
iodine (I2) (thyroid perxodiase, TPO), and released
into the lumen. (TSH uptake 250 times), (ClO-4, SCN-
Inhibit uptake)
 Organification: Iodine attaches to tyrosine, (20
tyrosine residues) mediated by TPO enzymes, forming
T1 (monoiodotyrosine, or MIT), and T2 (diiodotyrosine, or
DIT) (Stimulated by TSH, Inhibited by Thiouracil)
 Coupling: Iodinated tyrosines link together to form T3
Synthesis of Thyroid Hormone
Synthesis of Thyroid Hormone
Transport and Regulation of TH
 T4 and T3 bind to thyroxine-binding
globulins (TBGs) produced by the liver
 Both bind to target receptors, but T3 is ten
times more active than T4
 Peripheral tissues convert T4 to T3
enzymetically
 Mechanisms of activity are similar to
steroids
 Regulation is by negative feedback
 Hypothalamic thyrotropin-releasing
hormone (TRH) can overcome the
negative feedback in high energy
Effects of Thyroid Hormone
 Calorigenic Action
 Increase oxygen consumption of all
metabolically active tissues, Increases
BMR
 The exceptions are the adult brain,
testes, uterus, lymph nodes, spleen, and
anterior pituitary
 Carbohydrate Metabolism
 Increases absorption of glucose from GIT
 Increases utilization of glucose
 Increases insulin secretion
 Increases glycolysis in liver
 Protein Metabolism
 Increases protein synthesis by increasing
translation and transcritption
 Normal amounts anabolic effects
Effects of Thyroid Hormone
 Fat Metabolism
 Mobilizes Fatty acids from Fat source
 Increases circulating FFA levels
 Accelerates FFA oxidation
 Hypersecretions decrease the conc. of
Cholesterol, triglycerides and
phospholipids in plasma
 Water and Mineral metabolism
 Promotes demineralization of bones
 Increases excretion of Calcium and
phosphate in urine
 Causes diuresis
 Vitamins Metabolism
 Increased demands of Vitamins as they are
 Effects of Thyroid Hormone
 Effects on CVS
 Increased blood flow to skin
 Increased cardiac output
 Increased Heart Rate due to direct
stimulatory effect by catecholamines
because of increased adrenergic receptors
 Effects on Respiratory System
 Increases rate of Oxygen consumption
 Increases rate and depth of respiration
 Effects on CNS
 Increases synaptic activity
 Hyperthyroidism causes anxiety and
nervousness
 Hypothyroidism causes mental retardation
in children
Effects of Thyroid Hormone
 Effects on GIT
 Increases appetite
 Increases food intake
 Increased rate of Absorption
 Increases secretion digestive juices
 Increases GIT motility
 Hyperthyroidism causes diarrhea
 Effects on Reproductive system
 Essential for normal reproduction
 Hypothyroidism leads to reduces fertility
 Hypo  Decreased libido in both male
and female
 Impotence in men (hyperthoyroidism)
Hypothyroidism
 Hypothyroid disorders
 Thyroid gland defect
 Inadequate TSH or TRH release.
 Thyroid gland removed surgically
 Inadequate dietary iodine    
 In adults, the full-blown hypothyroid
syndrome is called Myxedema (Mucous
swelling)
 Symptoms
 Low metabolic rate;
 Feeling chilled;
 Constipation;
 Thick, dry skin and puffy eyes;
Goiter
 If myxedema results from lack of iodine,
the thyroid gland enlarges and protrudes,
a condition called goiter.

 Depending on the cause, myxedema can

be reversed by iodine supplements or
Cretinism
 Severe hypothyroidism in infants is called
cretinism
 Mental retardation
 Short, disproportionately sized body
 Thick tongue and neck.
 Cretinism may reflect a genetic deficiency
of the fetal thyroid gland or maternal
factors, such as lack of dietary iodine.
 It is preventable by thyroid hormone
replacement therapy if diagnosed early
enough, but once developmental
abnormalities and mental retardation
appear, they are not reversible.
 Hyperthyroidism
 Graves’ disease:
 An autoimmune disease
 Serum IgG antibodies (TSI or TSAb) bind to
TSH Receptors and stimulate thyroid
hormone production
 Symptoms include
 Elevated metabolic rate;
 sweating; rapid, irregular heartbeat;
 nervousness; and weight loss despite
adequate food intake.
 Exophthalmos, protrusion of the eyeballs,
may occur if the tissue behind the eyes
becomes edematous and then fibrous
Thyroid Disorders

Exopht ha lmo s Cretinism

 Calcitonin
 A peptide hormone produced by the
parafollicular, or C, cells
 Lowers blood calcium levels in children
 Antagonist to parathyroid hormone (PTH)
 Functions
 Calcitonin targets the skeleton, where it:
 Inhibits osteoclast activity and release of
calcium from the bone matrix
 Stimulates calcium uptake and
incorporation into the bone matrix
 Regulated by a humoral (calcium ion
concentration in the blood) negative
feedback mechanism
2+
Pharmacy Application: Therapeutic effects of Calcitonin

 Paget’s disease
 Characterized by a significant increase in
osteoclast activity and, thus, a high rate
of bone turnover and hypercalcemia
 Treatment
 Cibacalcin®, (synthetic human
calcitonin)
 Miacalcin, (Salmon calcitonin )
 Postmenopausal osteoporosis
 Salmon calcitonin, which is 20 times
more potent than human calcitonin, has
also been approved for therapeutic use
in patients with postmenopausal
 Parathyroid Glands

 Tiny glands embedded in the posterior

aspect of the thyroid
 Cells are arranged in cords containing
oxyphil and chief cells
 Chief (principal) cells secrete PTH
 PTH (parathormone) regulates calcium
balance in the blood
 Normally four in number but up to 8 are
reported
Parathyroid Glands
Calcium & Phosphate Metabolism
 Calcium accounts for 2% of body weight
 Normal body calcium levels 9.4mg/dl or
2.4mmol/L
 <0.1% in ECF, <1% in cells, remaining
almost 99% in bones
 Physiological Actions:
 Transmission of nerve impulse
 Muscle contraction
 Blood clotting
 Bone formation
 Hypocalcemia Causes Nervous System
excitement and Tetany
 Hypercalcemia Depresses Nervous System
and Muscle Activity
Calcium Metabolism
Calcium and Vitamin D:
Formation of Active Vitamin D:

25-Hydroxylase (-
)

PTH 1-α -Hydroxylase 24-Hydroxylase

(-
) (Inactive)
(Active)
Functions of Active Vitamin D:
 Promote Intestinal Calcium Absorption
 It binds with its nuclear receptor in the
brush border of intestinal epithelial cells
and induces the expression of
 Calcium-binding protein (CaBP) (Rate of
Ca2+ abs. α CaBP)
 Ca2+- ATPase
 Decreases renal Calcium and Phosphate
Excretion
 Vitamin D in smaller quantities promotes
bone calcification
 The administration of extreme quantities of
vitamin D causes absorption of bone
 Osteomalacia (Adults) (Softening of
 Parathyroid Hormone (Parathormone)
 Preprohormone-110AA, Prohormone-90 AA,
Hormone-84 AA
 34-AA containing fragments have also been
isolated adjacent to N-terminus
 Secretion of PTH
 PTH release is controlled serum Ca2+ through
Negative feed back mechanism
 Secretion is through 2nd Messenger cAMP by
parathyroid gland
 Actions of Parathyroid Hormone
 It is the principal regulator of calcium
metabolism. Its overall effects include:
 Increase in blood levels of calcium
 Decrease in blood levels of phosphate
Parathyroid Hormone
 PTH increases Ca2+ levels in blood by
stimulating three target organs:
 The skeleton, (Calcium reserves)
 The kidneys,
 The intestine
 PTH release increases Ca2+ in the blood as it:
 Stimulates osteoclasts to digest bone
matrix
 Enhances the reabsorption of Ca2+ and the
excretion of phosphate by the kidneys
 Increases absorption of Ca2+ by intestinal
mucosal cells with the help of vitamin D
that is activated by PTH in kidneys
 Rising Ca2+ in the blood inhibits PTH release
Effects of Parathyroid Hormone
Hypocalcaemia
Adrenal (Suprarenal) Glands
 Adrenal glands – paired, pyramid-shaped
organs at top of the kidneys, weigh 4 g
each.
 Structurally and functionally, they are two
glands in one
 Adrenal medulla – nervous tissue that
acts as part of the Sympathetic NS (20%
of gland)
 Adrenal cortex – bulk of glandular tissue
derived from embryonic mesoderm
encapsulating medulla
Adrenal Cortex
 Synthesizes and releases steroid
hormones called corticosteroids
 More than 24 corticosteroids are
synthesized
 Different corticosteroids are produced in
each of the three layers
 Zona glomerulosa – mineralocorticoids
(chiefly aldosterone)
 Zona fasciculata – glucocorticoids
(chiefly cortisol)
 Zona reticularis – gonadocorticoids
(chiefly androgens)
Bio-Synthesis of steroid Hormones
 Acetyl Co-A Liver Cholesterol
(Precursor)
 De Novo in Adrenal Cortex but not in
placenta
Adrenal Cortex
Mineralocorticoids
 Regulation of the electrolyte
concentrations of extracellular fluids
particularly Na+ and K+
 Aldosterone (95 %) – most important
mineralocorticoid
 Maintains Na+ balance by reducing
excretion of sodium from the body
 Stimulates reabsorption of Na+ by the
kidneys
 Promotes the synthesis of proteins
needed for reabsorption of Na+ i.e
Na+/K+ -ATPase
 Its effects last for 20 minutes
Mineralocorticoids
The Four Mechanisms of Aldosterone Secretion
 Renin-angiotensin mechanism – kidneys
release renin, which is converted into
angiotensin II that in turn stimulates
aldosterone release
 Plasma concentration of sodium and
potassium – directly influences the zona
glomerulosa cells
 ACTH – causes small increases of
aldosterone during stress
 Atrial natriuretic peptide (ANP) – inhibits
activity of the zona glomerulosa
The Four Mechanisms of Aldosterone Secretion
Glucocorticoids
 Glucocorticoid hormones include
 cortisol (hydrocortisone)
 cortisone, and
 corticosterone,
 Only cortisol is secreted in significant amounts
in humans.
 As for all steroid hormones, the basic
mechanism of glucocorticoid activity on target
cells is to modify gene activity
 Cortisol
 Help the body resist stress by:
 Keeping blood sugar levels relatively constant
 Maintaining blood volume and preventing water
shift into tissue
 Cortisol provokes:
Excessive Levels of Glucocorticoids
 Triggered in turn by the hypothalamic
releasing hormone CRH.
 Cortisol release is promoted by ACTH,
 Rising cortisol levels feed back to act on
both the hypothalamus and the anterior
pituitary, preventing CRH release and
shutting off ACTH and cortisol secretion.
 Excessive levels of glucocorticoids:
 Depress cartilage and bone formation
 Inhibit inflammation
 Depress the immune system
 Promote changes in cardiovascular,
neural, and gastrointestinal function
Cushing’s syndrome
 Glucocorticoid excess, Cushing’s
syndrome,
 ACTH-releasing pituitary tumor (in which
case, it is called Cushing’s disease);
 ACTH-releasing malignancy of the lungs,
pancreas, or kidneys; or
 A tumor of the adrenal cortex.
 Most often results from the clinical
administration of pharmacological doses
(doses higher than those found in the
body) of glucocorticoid drugs.
 The syndrome is characterized by
 persistent hyperglycemia (steroid
diabetes),
 dramatic losses in muscle and bone
 Cushing’s syndrome
 The so-called cushingoid signs include
 Swollen “moon” face,
 Redistribution of fat to the abdomen and
the posterior neck (causing a “buffalo
hump”),
 Tendency to bruise, and
 Poor wound healing.
 Because of enhanced anti-inflammatory
effects,
 infections may become overwhelmingly
severe before producing recognizable
symptoms.
 The only treatment is removal of the cause—
Addison’s disease
 The major hyposecretory disorder of the
adrenal cortex, usually involves
 Deficits in both glucocorticoids and
mineralocorticoids.
 Its victims tend to
 Lose weight;
 Plasma glucose and sodium levels drop
and potassium levels rise.
 Severe dehydration and hypotension are
common.
 Treatment
 Corticosteroid replacement therapy at
physiological doses (doses typical of
Gonadocorticoids (Sex Hormones)
 Most gonadocorticoids secreted are
androgens (male sex hormones), and the
most important one is testosterone
 Androgens contribute to:
 The onset of puberty
 The appearance of secondary sex
characteristics
 Sex drive in females
 Androgens can be converted into
estrogens after menopause
Adrenal Medulla
 Made up of chromaffin cells that secrete
epinephrine and norepinephrine
 Secretion of these hormones causes:
 Blood glucose levels to rise
 Blood vessels to constrict
 The heart to beat faster
 Blood to be diverted to the brain, heart,
and skeletal muscle

PLAY InterActive Physiology®: Endocrine System: Response to Stress

Adrenal Medulla
 Epinephrine is the more potent stimulator
of the heart and metabolic activities
 Norepinephrine is more influential on
peripheral vasoconstriction and blood
pressure
Stress and the Adrenal Gland
Pancreas
 A triangular gland, which has both
exocrine and endocrine cells, located
behind the stomach
 Acinar cells produce an enzyme-rich juice
used for digestion (exocrine product)
 Pancreatic islets (islets of Langerhans)
produce hormones (endocrine products)
 The islets contain two major cell types:
 Alpha (α) cells that produce glucagon
 Beta (β) cells that produce insulin
Glucagon
 A 29-amino-acid polypeptide hormone
that is a potent hyperglycemic agent
 Its major target is the liver, where it
promotes:
 Glycogenolysis – the breakdown of
glycogen to glucose
 Gluconeogenesis – synthesis of glucose
from lactic acid and noncarbohydrates
 Release of glucose to the blood from
liver cells
Insulin
 A 51-amino-acid protein consisting of two
amino acid chains linked by disulfide
bonds
 Synthesized as part of proinsulin and then
excised by enzymes, releasing functional
insulin
 Insulin:
 Lowers blood glucose levels
 Enhances transport of glucose into body
cells
 Counters metabolic activity that would
enhance blood glucose levels
Effects of Insulin Binding
 The insulin receptor is a tyrosine kinase
enzyme
 After glucose enters a cell, insulin binding
triggers enzymatic activity that:
 Catalyzes the oxidation of glucose for
ATP production
 Polymerizes glucose to form glycogen
 Converts glucose to fat (particularly in
adipose tissue)
Regulation of Blood Glucose Levels
 The
hyperglyce
mic effects
of glucagon
and the
hypoglyce
mic effects
of insulin
Diabetes Mellitus (DM)
 Results from hyposecretion or
hypoactivity of insulin
 The three cardinal signs of DM are:
 Polyuria – huge urine output
 Polydipsia – excessive thirst
 Polyphagia – excessive hunger and food
consumption
 Hyperinsulinism – excessive insulin
secretion, resulting in hypoglycemia
Diabetes Mellitus (DM)
Gonads: Female
 Paired ovaries in the abdominopelvic
cavity produce estrogens and
progesterone
 They are responsible for:
 Maturation of the reproductive organs
 Appearance of secondary sexual
characteristics
 Breast development and cyclic changes
in the uterine mucosa
Gonads: Male
 Testes located in an extra-abdominal sac
(scrotum) produce testosterone
 Testosterone:
 Initiates maturation of male reproductive
organs
 Causes appearance of secondary sexual
characteristics and sex drive
 Is necessary for sperm production
 Maintains sex organs in their functional
state
Pineal Gland
 Small gland hanging from the roof of the
third ventricle of the brain
 Secretory product is melatonin
 Melatonin is involved with:
 Day/night cycles
 Physiological processes that show
rhythmic variations (body temperature,
sleep, appetite)
Thymus
 Lobulated gland located deep to the
sternum in the thorax
 Major hormonal products are
thymopoietins and thymosins
 These hormones are essential for the
development of the T lymphocytes (T
cells) of the immune system
Other Hormone-Producing Structures
 Heart – produces atrial natriuretic peptide
(ANP), which reduces blood pressure,
blood volume, and blood sodium
concentration
 Gastrointestinal tract – enteroendocrine
cells release local-acting digestive
hormones
 Placenta – releases hormones that
influence the course of pregnancy
Other Hormone-Producing Structures
 Kidneys – secrete erythropoietin, which
signals the production of red blood cells
 Skin – produces cholecalciferol, the
precursor of vitamin D
 Adipose tissue – releases leptin, which is
involved in the sensation of satiety, and
stimulates increased energy expenditure
Developmental Aspects
 Hormone-producing glands arise from all
three germ layers
 Endocrine glands derived from mesoderm
produce steroid hormones
 Endocrine organs operate smoothly
throughout life
 Most endocrine glands show structural
changes with age, but hormone
production may or may not be affected
Developmental Aspects
 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
 Female hormone production declines, the
ability to bear children ends, and
problems associated with estrogen
deficiency (e.g., osteoporosis) begin to
occur
 Testosterone also diminishes with age,
but effect is not usually seen until very
old age
Developmental Aspects
 GH levels decline with age and this
accounts for muscle atrophy with age
 Supplemental GH may spur muscle
growth, reduce body fat, and help
physique
 TH declines with age, causing lower basal
metabolic rates
 PTH levels remain fairly constant with
age, and lack of estrogen in women
makes them more vulnerable to bone-
demineralizing effects of PTH