Chapter 18

The Endocrine System

 Endocrine system
• Endo = inside
• crine = secrete
• hormon = to excite
– to get ~ 1# of endocrine tissue you would need to
collect ALL the endocrine tissue from ~4-5
adults

• Exocrine cells secrete their product into a

duct
 Homeostasis
• Works in conjunction w/
nervous system
• slower to react/effects last
longer
• endocrine glands include:
– pituitary, thyroid,
parathyroid, adrenal, pineal,
thymus, ORGANS -
pancreas, gonads,
hypothalamus
(neuroendocrine organ),
MINOR ORGANS - sm int.,
stomach, kidneys, heart,
adipose cells
 Paracrines
• locally acting chemicals that transfer
information from cell to cell within single
tissue
– These are not considered hormones since
hormones are long-distance chemical signals
 Hormone-target cell specificity
• A cell can only react to a H if it has a
receptor on its plasma membrane or in its
interior
• example: radio tuned to only pick up
specific signals although there are many
signals in the air concurrently
 3 factors effecting target cell
activation
• 1. Blood levels of the H
• 2. # of receptors for that H on or in target cells
• 3. affinity (strength) of bond b/t H & receptor
– up-regulation - target cells form more receptors in
response to decreased blood H levels
– down-regulation - prolonged exposure to high H [ ]
desensitizes the target cell by losing receptors so they
respond less vigorously to H stimulation
 Mechanism of Hormone action
• Hormones have their effect by altering cell
activity, not causing the activity
– alters plasma membrane permeability
– alters membrane potential thru open/closing ion
channels
– (+) synthesis of proteins/enzymes w/in cell
– activates/deactivates enzymes
– induces secretory activity
– stimulates mitosis
 Hormones
• Can be divided
into 3 groups:
– amino acid
derivatives
– peptide
hormones
– lipid
derivatives
 Amino Acid Derivatives
• Small molecules structurally related to amino
acids
• Synthesized from the amino acids tyrosine and
tryptophan
 Peptide Hormones
• Chains of amino acids
• Synthesized as prohormones:
– inactive molecules converted to active hormones
before or after secretion
 2 Groups of Peptide Hormones
• Group 1:
– glycoproteins:
• more than 200 amino acids long, with carbohydrate side chains:
– TSH, LH, FSH

• Group 2:
– all hormones secreted by:
• hypothalamus
• hypophysis
• heart
• thymus
• digestive tract
• pancreas
 2 Classes of Lipid Derivatives
• Eicosanoids:
– derived from arachidonic acid
• Steroid hormones:
– derived from cholesterol
 Eicosanoids
• act locally so are not always thought of as
Hs b/c they are not circulating in the blood
• examples:
– leukotrienes - signaling chemicals that mediate
inflammation & some allergic reactions
– prostaglandins - multiple functions including
raising of BP, enhancement of uterine
contractions, blood clotting, & inflammation
 Steroid Hormones
• Are lipids structurally similar to cholesterol
• Released by:
– reproductive organs
– adrenal cortex (corticosteroids)
– kidneys (calcitriol)
• Remain in circulation longer than peptide
hormones
• Are converted to soluble form, are absorbed
gradually by liver, & may be excreted in bile or
urine
 Hormone Concentrations in the Blood
• Hormones circulate in the blood in two forms –
free or bound
– Steroids and thyroid hormone are attached to plasma
proteins and remain in circulation much longer
– All others are unencumbered and remain functional
for less than one hour
• These are either absorbed & broken down by liver or
kidneys, are broken down by enzymes, or diffuse out of
the bloodstream to bind on target cells
 Mechanism of Hormone action
• A hormone must bind to a receptor to exert
its effect
• There are two ways in which this happens
– Second messenger mechanism
– Using intracellular receptor
 Catecholamines and Peptide Hormones

• Are not lipid soluble so unable to penetrate cell

membrane
• Bind to receptor proteins at outer surface of cell
membrane (extracellular receptors)
• Uses intracellular intermediary (second
messenger) to exert effects
cAMP as a second messenger
 Intracellular Intermediaries
• First messenger:
– leads to second messenger
– may act as enzyme activator, inhibitor, or cofactor
– results in change in rates of metabolic reactions
• Important Second Messengers
– Cyclic-AMP (cAMP):
• derivative of ATP
– Cyclic-GMP (cGMP):
• derivative of GTP
– Calcium ions
 Cascade Effect

• When the binding of a small number of

hormone molecules to membrane receptors
leads to thousands of second messengers in cell
• Magnifies effect of hormone on target cell
 G Protein
• Enzyme complex coupled to membrane receptor
• Involved in link between first messenger and
second messenger
– Binds GTP
• Activated when hormone binds to receptor at
membrane surface
• Changes concentration of second messenger
cyclic-AMP (cAMP) within cell
– Increased cAMP level accelerates metabolic activity
within cell
 Lower cAMP Levels
1. Adenylate cyclase activity is inhibited
2. Levels of cAMP decline
3. cAMP breakdown accelerates & cAMP
synthesis is prevented
 Eicosanoids & Steroid Hormones
• Are lipid soluble
• Diffuse across membrane to
bind to receptors in
cytoplasm or nucleus,
activating or inactivating
specific genes
• Alter rate of DNA
transcription in nucleus:
– change patterns of protein
synthesis
• Directly affect metabolic
activity and structure of
target cell
 Endocrine reflex Triggers
• NEGATIVE FEEDBACK SYSTEM
– humoral - PTH raises blood Ca, insulin,
aldosterone
– neural - SNS to adrenals, oxytocin/ADH
release from post. pituitary due to
hypothalamic (+)
– hormonal - “tropic” Hs from Ant. Pit. As
a result of the target gland raising H levels
in blood
Hypothalamus - a neuroendocrine organ

1. Secretes regulatory hormones:

– Special hormones control endocrine cells in
pituitary gland
2. Contains autonomic centers:
– Exert direct neural control over endocrine cells of
adrenal medullae
 Pituitary gland aka Hypophysis
• Found in sella turcica
• pea sized &
connected to
hypothalamus via
infundibulum
• secretes at least 9 Hs
– Master gland
• anterior (glandular)
& posterior
(neural)lobes
 Neurohypophysis
• Derived from hypothalamic tissue
• Connected to the hypothalamus via the infundibulum
• Does not synthesize its own hormones
– Stores those made in the hypothalamus
• Oxytocin & ADH

Adenohypophysis
• Formed from epithelial tissue originating from Rathke’s pouch
(oral mucosa)
• No neural connection to hypothalamus
• Synthesizes its own hormones
• Communicates via a vascular connection
– Primary capillary plexus in hypothalamus
– Secondary capillary plexus in ant. pituitary
Hypophyseal secretory effectors
 Activity of the Adenophypophysis
• The hypothalamus
sends a chemical
stimulus to the
anterior pituitary
– Releasing
hormones stimulate
the synthesis and
release of hormones
– Inhibiting
hormones shut off
the synthesis and
release of hormones
 Adenohypophyseal Hormones
• Tropic hormones
– 4 out of 6 are tropic (turn on/stimulatory)
– TSH, ACTH, FSH, LH

– All adenohypophyseal Hs affect their target

cells via a second messenger system
 Thyroid stimulating hormone
• TSH…thyrotropin
• Release triggered by thyrotropin-releasing
hormone (TRH)
• Somatostatin is released by hypothalamus
w/ increasing TSH levels to block release
 Adrenocorticotropic hormone
• ACTH…corticotropin
• Release triggered by corticotropin-releasing
hormone (CRH)
• (+) adrenal cortex to release corticosteroid
Hs; specifically those that help the body resist
stressors
 Gonadotropins
• Follicle stimulating hormone (FSH)
– AKA follitropin
– Stimulates gamete production (sperm & egg)
• Luteinizing hormone (LH)
– AKA lutotropin
– Promotes production of gonadal hormones
– Stimulates maturation of the ovarian follicle and then triggers
ovulation
– Stimulates interstitial cells of testes to produce testosterone…
AKA interstitial cell stimulating hormone (ICSH)
• Virtually non-existant in prepubescents
• Release regulated by gonadotropin-releasing hormone
(GnRH) & suppressed by rising levels of gonadal Hs
 Prolactin (PRL)
• AKA mammotropin
• Some people consider it a gonadotropin but structurally
similar to GH
• Well documented to (+) milk production in breasts
• May enhance testosterone production in males
• Release controlled by both prolactin-releasing hormone
(PRH)…thought to be serotonin & prolactin-inhibiting
hormone (PIH)…thought to be dopamine
– PIH dominates in males
– In women PRL levels rise & fall w/ estrogen levels (low
estrogen…(+) PIH release/high estrogen…(+) PRH…when just
prior to menstruation accounts for breast swelling & tenderness
 Growth hormone (GH)
• AKA Somatotropin (STH)
• Major targets are bone & sk mm cells
– (+) most body cells to grow & divide
– Encourages protein synthesis & use of fat for fuel
• Secretion is regulated by 2 hypothalamic Hs
– Growth hormone-releasing hormone (GHRH)
– Growth hormone-inhibiting hormone (GHIH)
• Aka somatostatin (also (-) other ant.pit. Hs, GI, &
pancreatic secretions—both endo & exocrine)
 Melanocyte Stimulating Hormone
• Also called melanotropin (MSH)
• Stimulates melanocytes to produce melanin
• Inhibited by dopamine
• Secreted during:
– fetal development
– early childhood
– pregnancy
– certain diseases
Summary: The Hormones of the Pituitary Gland

Table 18–2
 Neurohypophyseal Hormones
• ADH & Oxytocin
• Both composed of 9 Aas & are almost
identical
– Differ in only 2 of 9 AAs
 Antidiuretic hormone (ADH)
• Inhibits or prevents urine formation
• Hypothalamus has osmoreceptors to monitor blood
solute [ ]
– If too [ ] ADH is released which causes kidneys to resorb
more water
– Other (+) include: pain, hypotension, nicotine, morphine
– (-) by alcohol & caffeine
• At high blood [ ] ADH has a vasoconstrictive effect…
conditions such as severe blood loss cause ADH release
which causes a rise in BP
– Aka Vasopressin
 Diabetes insipidus
• Deficiency of ADH
• Leads to huge amounts of urine production
• Insipidus = tasteless…no glucosuria
• OK if thirst centers intact
– Dangerous in unconscious patients & w/head
injury
– Head trauma victims must be carefully
monitored
 Oxytocin
• A strong stimulant of uterine contraction
– Amounts higher during childbirth & w/nursing
– Stretching of the uterus & cervix sends afferent
signals to the hypothalamus…release of more
oxytocin
• Triggers milk “letdown” or ejection in
lactating breasts ) from PRL

– Both are positive feedback mechanisms

 Oxytocin, cont.
• Natural & synthetic drugs (pitocin) are used
to induce labor & speed it up
• Sometimes used to stop postpartum
bleeding (compressing of ruptures blood
vessels)
• May play role in sexual satisfaction &
orgasm in males & non-lacting females
– May promote nurturing/affectionate behavior in
non-sexual relationships…cuddling hormone
 Thyroid gland
• Butterfly shaped w/2 lobes connected by an isthmus
• Made up of 2 types of cells
– Follicle cells (simple cuboidal or squamous
epithelium) make up the follicle & produce a
glycoprotein called thyroglobulin
• The lumen of the follicle contains thyroglobulin w/
attached Iodine molecules
• Thyroid hormone (TH) is produced from the
iodinated thyroglobulin
– Parafollicular cells are interspersed b/t follicular
epithelium & the CT separating the follicles
• Calcitonin is produced here
Thyroid Gland

Figure 18–10a, b
 Thyroid Hormone (TH)
• The body’s major metabolic hormone
• Actually 2 different Hs:
– T4 or thyroxin (major H secreted by follicle
cells)
– T3 or triiodothyronine (most formed at target
tissues by converting T4 to T3)
• Affects virtually every body cell except
adult brain, spleen, testes, uterus, & the
thyroid gland itself
 TH, cont.
• Stimulates enzymes concerned w/glucose
oxidation…increases BMR
• Increases body heat production (calorigenic
effect)
• Increases # of adrenergic receptors in BVs so it
is important in maintaining BP
• Regulator of tissue growth & development (esp
skeletal, nervous, & reproductive system)also
affects CV system, mm system, GI system, &
hydration of skin
Synthesis of Thyroid Hormone
 TH regulation
• Falling thyroxin blood levels trigger release of
TSH…thyroxin
• TSH levels are usually lower during the day, peak
just b/f sleep, & remain high during the night
• Conditions that increase the body’s energy
requirements (pregnancy, prolonged cold) cause
hypothalamus to release thyrotropin-releasing
hormone (TRH)…TSH release from ant. pit.
– TRH overcomes the (-) feedback controls
• Somatostatin, rising levels of glucocorticoids &
sex Hs (estrogens & testosterone), & excessively
high blood iodide [ ] all (-) TSH release
 Thyroid disorders
• Hypothyroid
– Myxedema – low BMR, feel cold, constipation, thick/dry
skin, puffy eyes, edema, lethargy, mental sluggishness
• if it is a result of iodine insufficiency the thyroid gland enlarges to
form a colloidal goiter (follicle cells produce colloid & store it but
cannot iodinate it…TSH secretion increases…more colloid produced
but no TH…after a while thyroid cells ‘burn out’ & gland atrophies)
– Cretinism – severe hypothyroid in infants; usually mentally
retarded, short, disproportioned body, thick tongue; may be a
genetic defect in thyroid or inadequate maternal dietary iodine
intake
• Hyperthyroid
– Grave’s disease – believed to be autoimmune; increased
BMR, sweating, rapid heart rate, nervousness, weight loss,
exophthalmos (from edematous accumulation b/h eyes)
Exophthalmos Colloidal goiter
 Calcitonin
• Produced by the parafollicular (C-clear) cells
• Antagonist to PTH by lowering blood calcium levels
– (+) Ca uptake & incorporation into bone matrix
– (-) osteoclast activity…bone resorption
• Excessive blood Ca levels (~20% above normal) (+)
calcitonin release
• Declining blood Ca levels (-) release
• Seems more important in childhood w/rapidly
growing bones & rapidly changing blood Ca levels
• In adults it is a weak hypocalcemic agent
 Parathyroid glands
• Usually 4 BB sized
glands found on the
posterior aspect of the
thyroid gland
• Secretion of PTH is by
chief cells
• As many as 8 glands
have already been
found and some have
even been found in
other areas of the neck
& thorax
 Parathyroid hormone (PTH)

• AKA parathormone
• Single most important H controlling Ca balance in
the blood
• (+) from falling blood Ca levels
• (-) from hypercalcemia
• PTH release (+) 3 target organs…
 PTH, cont.
• PTH release (+)
– Osteoclasts – to digest bony matrix & release Ca &
phosphates to the blood
– Kidneys – to enhance reabsorption of Ca (&
excretion of phosphates)
– Intestine – increases absorption of Ca by intestinal
mucosa cells… PTH causes conversion of vitamin D
from the inactive form absorbed in the skin into its
active form, calcitriol
• Vit D is needed to absorb Ca from ingested food
 Adrenal glands
• AKA suprarenal glands
• Dual glands
– Adrenal medulla –
nervous tissue (SNS)
– Adrenal cortex –
glandular tissue derived
from embryonic
mesoderm; majority of
gland
• All adrenal hormones
help us cope with
extreme (stressful)
situations
 Adrenal cortex
• Produce over 2 dozen steroid Hs called corticosteroids
• 3 distinct layers or zones of cells
– Zona glomerulosa – produce mineralocorticoids
• Balance of water & minerals in body
– Zona fasciculata – produce glucocorticoids
• Metabolism of body cells, gluconeogenesis, anti-inflammatory
– Zona reticularis – produce gonadocorticoids
• Insignificant in adults, female libido?
• All corticosteroids are produced by some degree in all
3 layers
 Mineralocorticoids
• Aldosterone is the most potent (95% of total);
(+) distal tubules in kidneys to reabsorb Na ions
from the forming urine & return them to
bloodstream (same result of Na reabsorption
from perspiration, saliva, & gastric juices)
– Remember…where Na goes, water will follow
– (+) of aldosterone secretion: hyperkalemia,
hyponatremia, decreasing blood volume & decreasing
BP
– (-) of secretion is due to the reverse factors
– ACTH has little to no effect on aldosterone release
 Glucocorticoids

• Cortisol is the most important; help keep blood

glucose levels constant w/sporadic meal
patterns, very active responding to stress, anti-
inflammatory
– Secretion promoted by ACTH
– Any stress will cause override of (-) feedback that
normally would reduce cortisol levels
– Cortisol also enhances epinephrine’s
vasoconstrictive effects to increase BP…ensuring
circulatory efficiency to help distribute nutrients
 Glucocorticoids, cont.
• Excessive levels of cortisone:
– Depress cartilage & bone formation
– (-) inflammation by preventing vasodilation
– Depresses the immune system
– Promotes changes in cardiovascular, neural, & GI
function

– Frequently are the drug of choice for chronic

inflammatory diseases
 Cortisone diseases
• Hypersecretion
– Cushing’s disease (syndrome) – most often results from
overmedication; also adrenal cortex tumors or tumors of
pituitary causing release of ACTH
• Hyperglycemia, loss of mm/bone protein, salt/water
retention…”moon face”, “buffalo hump” from fat redistribution, easy
bruising, poor wound healing…tx w/ discontinuing drugs or removal
of tumor
• Hyposecretion
– Addison’s disease – usually deficits of both glucocorticoids
(cortisone) & mineralocorticoids (aldosterone)
• Weight loss, drop of plasma glucose & Na levels, rise in K levels…
dehydration, hypotension…tx w/corticosteroid replacement
Cushing Syndrome
 Gonadocorticoids
• AKA sex hormones
• Most are androgens; testosterone is most
important
• Minimal amounts of estrogen production
• Not much function in the adult…adrenal
androgens seem to be related to the female sex
drive (libido)
– May convert to estrogens after menopause when
ovarian estrogens are no longer produced
 Adrenal medulla

• Chromaffin cells are modified ganglionic

sympathetic neurons that secrete the
catecholamines
– Epinephrine
– Norepinephrine
 Catecholamines
• SNS fibers w/ fight or flight
– Blood sugar levels rise, vasoconstriction, tachycardia,
diversion of blood from nonessential organs to brain, heart, &
skeletal mm
• Catecholamines released after SNS (+) prolong
response; response is brief in relation to effects of
adrenocortical Hs
• 80% of Hs released are epi, 20% are norepi
– Epi is more potent for (+) heart & metabolic activities
– Norepi is more potent for (+)vasoconstriction & BP
– Epi is often used clinically as a heart stimulant and a
bronchioldilator during asthma attacks
 Pineal Gland

• Small gland hanging from the roof of the third

ventricle of the brain
• Secretory product is melatonin
• Melatonin is involved with:
– Inhibits reproductive functions
– Protects against free radical formation
– Day/night cycles & physiological processes that show
rhythmic variations (body temperature, sleep,
appetite)
 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 four cell types:
– Alpha () cells that produce glucagon
– Beta () cells that produce insulin
– Delta ( ) cells that produce somatostatin
– F-cells secrete pancreatic polypeptide (PP) – (-) g. bladder
 Insulin
• Produced by beta cells (islets of Langerhans)
• Major effect is lowering of blood sugar; also
affects protein & fat metabolism
• Insulin enhances membrane transport of glucose
into body cells like mm & fat cells…not liver,
brain, & kidney tissue--these have easy access to
glucose regardless of insulin levels
• Main (+) is hyperglycemia
– Any hyperglycemic H can also (+) release: glucagon,
epi, GH, thyroxine, or glucocorticoids—all are called
into action as blood glucose levels drop
 Glucagon
• Produced by alpha cells (islets of Langerhans)
• Major target is the liver
– Promotes glycogenolysis; gluconeogenesis from
lactic acid, fats & AAs
• 1 molecule of glucagon can cause the release 100
million molecules of glucose in to the blood
• Secretion (+) by falling blood sugar levels
• Secretion (-) by rise in blood sugar &
somatostatin
 Diabetes mellitus (DM)
• Hyposecretion or inactivity of insulin
• 3 cardinal signs
– Polyuria – decreased blood volume &
dehydration
– Polydipsia – thirst centers (+) from
dehydration
– Polyphagia – b/c present glucose cannot be
used & body starts breaking down fat &
protein stores for energy metabolism
 Gonads: Male
• Testes located in an extra-abdominal sac (scrotum) produce
testosterone & Inhibin (sperm maturation)
• 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

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
 Thymus

• Lobulated gland located deep to the

sternum in the thorax
• Major hormonal product is thymosin
• This hormone is 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
• Kidneys – secrete erythropoietin, which signals the production of
red blood cells; & renin which is a powerful vasoconstrictor
• 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;
resistin – reduces insulin sensitivity
Interaction of Hormones at Target Cells

• Four types of hormone interaction

– Permissiveness – one hormone cannot exert its
effects without another hormone being present
– Synergism – more than one hormone produces the
same effects on a target cell
– Antagonism – one or more hormones opposes the
action of another hormone
– Integration – hormones produce different &
complementary effects
General Adaptation Syndrome (GAS)
• AKA stress response
• How bodies respond to
stress-causing factors
• Divided into 3 phases:
1.alarm phase
2.resistance phase
3.exhaustion phase

Figure 18–18
 Alarm Phase
• Is an immediate response to stress
directed by ANS
• Energy reserves mobilized (glucose)
• “Fight or flight” responses
• Dominant hormone is epinephrine
 7 Characteristics of Alarm Phase
1. Increased mental alertness
2. Increased energy consumption
3. Mobilization of energy reserves (glycogen and lipids)
4. Circulation changes:
– increased blood flow to skeletal muscles
– decreased blood flow to skin, kidneys, and digestive
organs
5. Drastic reduction in digestion and urine production
6. Increased sweat gland secretion
7. Increases in blood pressure, heart rate, and respiratory
rate
 Resistance Phase
• Entered if stress lasts longer than few hours
• Dominant hormones are glucocorticoids
• Energy demands remain high
• Glycogen reserves nearly exhausted after
several hours of stress
 Effects of Resistance Phase
1. Mobilize remaining lipid and protein
reserves
2. Conserve glucose for neural tissues
3. Elevate and stabilize blood glucose
concentrations
4. Conserve salts, water, and loss of K+, H+
 Exhaustion Phase
• Begins when homeostatic regulation breaks
down
• Failure of 1 or more organ systems will
prove fatal
• Mineral imbalance
 Interactions between
Endocrine and Other Systems

Figure 18–19