Endocrine system has three components:
1) glands: secrete chemical messengers into blood
2) messengers: the chemical messengers themselves, or “hormones”
3) target cells/organs: respond to the messengers
5 Functions of the ES:
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1) differentiate reproductive & CNS in fetus
2) stimulate sequential growth & development in childhood & adolescence
3) coordinate male & female reproductive systems (making reproduction possible)
4) maintain homeostasis through life span
5) initiate corrective/adaptive responses when emergencies occur
 This includes neuroendocrine responses to stressors. There is an integrative
system between the endocrine, nervous and immune system (neuroendocrine
hormones affect immune system, immune components regulate neuroendocrine
response). This is why some stressful events cause emotional arousal while
others (such as a minor infection) can go unnoticed by us.
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4 Characteristics of Hormones P696
1) Hormones have specific rates & rhythms of secretion. Three basic secretion patterns are
circadian/diurnal, pulsatile/cyclic, and patterns that depend on levels of circulating
substrates.
2) Hormones operate in feedback systems (negative or positive) to maintain homeostasis
3) Hormones affect ONLY cells with the correct receptors for that hormone. Those cells
are then activated to initiate specific cell functions/activities.
4) Hormones are either excreted by the kidneys or metabolized by the liver (liver
inactivates hormones & makes them H2O soluble for excretion)
3 Ways by Which Hormones are Regulated
P697
1) chemical factors (blood sugar or Ca+ levels)
2) neural control
a. adrenal gland releases epinephrine when sympathetic division is activated in
response to stress
b. environmental stimuli and circadian influences
3) endocrine factors (a hormone from one gland controls another gland)
a. negative feedback: levels of one type of hormone influence the level of other
types of hormones
2 Types of Hormones to Consider
P698
1) Water-soluble: These hormones circulate freely and include protein hormones. Because
they are “unbound” they decompose quickly. They use a messenger to activate target
cells. Includes: insulin, pituitary, hypothalamic and parathyroid.
2) Lipid-soluble: These hormones are not “free” but transported by carrier proteins. Since
they are lipid soluble, they can cross cell membranes freely and bring about the desired
change. Includes: steroids such as cortisol and adrenal androgens.
What is a target cell and how does it work? P699
 Target cells have 2 functions: bind with the correct hormone and then initiate
intracellular changes. A target cell has the ability to adjust its sensitivity to signaling

hormones. The target cell does this by adjusting the number of receptors it has in its
membrane (thereby affecting how many hormones can bind to the cell):
o Up regulation: when there are low amounts of hormones, the target cell will
increase the # of receptors on its membrane
o Down regulation: when there are high amounts of hormones, the target cell will
decrease the # of receptors on its membrane
Once the TC binds to the correct hormone, three effects can occur:
o Direct Effects: obvious changes in cell function that specifically result from
stimulation by a hormone
o Permissive Effects: less obvious changes, hormone-induced, this change will
facilitate the maximum response/functioning of the cell
o Pharmacologic Effects: changes seen only when there is a very high hormone
level, may not reflect the actions of the hormone at normal levels (example: at
normal level ADH increases H2O absorption but at high levels it causes
vasoconstriction)
What’s going on at the cellular level? P699 (bottom)-703
 Lipid soluble hormones:
o diffuse through membrane on target cell
o bind to receptors (cytosolic or nuclear) and form a hormone-receptor complex
o hormone-receptor complex binds to a specific region in the DNA, altering the
expression of a specific gene
o transcription is triggered; the resulting mRNA moves to cytosol where it
associates with a ribosome and synthesizes a new protein
o new protein produces specific effects on the target cell
 Water soluble hormones: these can’t go directly across membranes so they undergo
more steps than lipid soluble hormones
o First Messenger: located on the target cell membrane, this is the first receptor
that a water soluble hormone interacts with
 There are 3 types and each type will determine what hormone can bind to
it: 1) G-protein receptors (most hormones bind to this receptor), 2) ionchannel receptors and 3) enzyme receptors (insulin binds to this
receptor).
o Second Messenger: after the hormone has bound to the first messenger, the
hormone/receptor complex then activates a second messenger (Ca++, cAMP,
cGMP, DAG, etc. ---> these are 2nd messengers)
 NOTE: different hormones will activate different second messengers
o After a couple more activation steps, the final result is activation of an
intracellular enzyme (such as protein kinase A or C), which leads to alterations in
gene transcription
o Gene transcription results in target cell response to the hormone
Hypothalamus: Function & Anatomy P703-704
 Location: see Fig 20-8 on P705 (right above the brain stem, connected to the pituitary
gland by the infundibular stem)
 Function: neurosecretory cells synthesize/secrete the hypothalamic hormones then
send these hormones to the pituitary for storage

o ADH and oxytocin are sent to the posterior pituitary by way of the
hypothalamohypophysial nerve tract (long word, easy concept)
o GH, ACTH, TSH, gonadotropic hormones, MSH and PRL are sent to the anterior
pituitary by way of the portal osmoreceptor blood vessels
NOTE: The hypothalamic-pituitary system forms the structural basis for CNS integration
of the neurologic & endocrine systems (in other words: it’s a critical integrative system:
nervous system regulates hypothalamus, hypothalamus regulates pituitary).
Pineal Gland: F&A
P704
 Location: see Fig 20-8 on P705
 Function: secretes melatonin
o Nerve pathways in the hypothalamus control the pineal gland
o Melatonin release is stimulated by exposure to dark & inhibited by light exposure
(regulates circadian rhythms)
o It also plays a role in regulating the reproductive system (onset of puberty) and
immune regulation
Pituitary Gland: F&A
P704-708
 Location: see Fig 20-8 on P705 (below the hypothalamus, connected by infundibular
stem)
 Function varies on anterior/posterior lobe and the hormones being released from each
lobe:
o Anterior Lobe (adenohypophysis): neurotransmitters & releasing factors
secreted by hypothalamus regulate this lobe, hormones secreted include:
 ACTH (adrenocorticotropic hormone): controls production/secretion of
some adrenal cortex hormones
 MSH (melanocyte-stimulating hormone): influences formation and
deposition of melanin pigment
 TSH (thyroid-stimulating hormone): stimulates the thyroid to produce T3
and T4, which control body’s metabolism
 PRL: prolactin, which induces milk production during lactation
 Gonadotropic hormones (FSH, LH, ICSH): reproductive hormones
 HGH (somatotropin): growth hormone secretion, promotes growth in
bone & muscle
 NOTE: This is the same as GH (growth hormone) except more
specific “human growth hormone”
 NOTE: GnRH (gonadotropin-releasing hormone) increases GH
secretion, somatostatin inhibits it
 Regulation is achieved by 1) feedback of hypothalamic releasinginhibitory hormones, 2) feedback from target gland hormones, and 3)
direct effects of neurotransmitters
 To gain a more specific understanding, study Table 20-6 on P708
o Posterior Lobe (neurohypophysis): derived from axons that originate in the
hypothalamus, secretes two hormones:
 ADH (antidiuretic hormone): regulates water reabsorption in kidneys so
it can be returned to bloodstream
 NOTE: also called a vasopressin b/c at high doses it triggers
vasoconstriction



Factors that regulate secretion:
o Osmoreceptors in hypothalamus: osmoreceptors respond
to increased osmolality and in this case, they control thirst
(osmolality increases = ADH secretion increases)
o Mechanoreceptors in left atrium and carotid/aortic arches
(intravascular volume increases = ADH secretion decreases)
o Other factors that increase secretion: stress, trauama, pain,
exercise, nausea
o Other factors that decrease secretion hypertension,
estrogen, progesterone, and alcohol
Oxytocin: simulates contraction of smooth muscles in uterus (pregnancy)
and contractile cells around the ducts of mammary glands (lactation)
 Mechanism of stimulation and diuretic function similar to that of
ADH
 Much of its effects are still being explored in both sexes.
NOTE: main stimulus for both hormones is glutamate for excitatory, GABA
for inhibitory
Thyroid Gland: F&A
P709 -711
 Location: Fig 20-11 on P709, two lobes that lie on either side of trachea, below thyroid
cartilage
 Function: controls rates of metabolic processes through the body
 Releases 3 hormones:
o Calcitonin: controls homeostasis of blood Ca+ level and inhibits bone breakdown
(increase in Ca+ level = increase in Calcitonin release = decrease bone
breakdown)
o T4 (thyroxine): this + T3 controls metabolic processes in your body
o T3 (triiodothyronine): has 3 times the biologic activity of T4
 The production of T4 and T3 is monitored by TSH (which is stored in the pituitary
gland). TSH stimulates the thyroid to produce T4/T3 by 1) low serum iodide levels or 2)
by drugs interfering with the thyroid gland’s uptake of iodide from the blood. The
effects of TSH when it stimulates the gland is 1) immediate increase in release of thyroid
hormones, 2) increase in iodide uptake/oxidation, 3) increase in thyroid hormone
synthesis and 4) an increase in synthesis/secretion of prostaglandins.
 NOTE: there is a 2/3 month supply of hormones stored in the cell vacuoles of thyroid so
malfunction in this gland can be serious
Parathyroid Glands: F&A
P711-712
 Location: two pairs, on posterior surface of thyroid
 Function: produces PTH (parathyroid hormone), which controls serum Ca+ levels
 How does PTH regulate Ca+ levels?
o It acts directly on bone (activates osteoclasts, which will release Ca+ into
bloodstream)
o Acts directly on kidneys (increases reabsorption of Ca+, decreases absorption of
phosphorus)
o In the kidney, it stimulates synthesis of active Vit D, which increases Ca+
absorption in intestines

NOTE: Two cell types: 1) chief/principal (synthesize most of the parathormone) and
oxyphil cells (synthesize reserve hormone)
Endocrine Pancreas: F&A
P712-715
 Location: behind stomach, between spleen and duodenum
 Function: exocrine (produces digestive enzymes) and endocrine (produces hormones,
makes up 1/2% of pancreatic tissue), pancreas serves as key player in metabolic
processes in body. The parasympathetic system stimulates hormonal
secretion/sympathetic system inhibits secretion.
 Structure: Islet of Langerhans are clusters of cells in the pancreatic tissue that house
three types of hormone-producing cells:
o Alpha: secretes glucagon
 High glucose levels = inhibits glucagon secretion
 Acts in the liver to increase blood glucose by stimulating glycogenolysis
(breakdown of glycogen)/gluconeogenesis (generation of glucose)
 It is an antagonist to insulin
o Beta: secrete insulin
 Increase blood glucose level = increase insulin secretion
 Insulin facilitates the rate of glucose uptake into many cells in the body (in
other words, it decreases glucose levels). It is an anabolic (building up)
hormone that promotes the synthesis of proteins, carbohydrates, lipids
and nucleic acids.
 If you destroy these cells, you develop type I diabetes mellitus.
o Delta: secrete somatostatin & gastrin
 Little is known but is believed to regulate alpha and beta cell function
within the ilets
Adrenal Glands: F&A
P715-720
 Location: paired, located behind the peritoneum, on top of kidney
 Function: the cortex and medulla produce/secrete many hormones that are essential to
body function
 Cortex: makes up 80% of the weight of the gland
o Divided into 3 sections:
 Zona glomerulosa: outermost layer, produces mineralocorticods
(aldosterone)
 Zona fasciculate: middle later, produces glucocorticoids (cortisol)
 Zona reticularis: innermost layer, produces other mineralocorticoids
(adrenal androgens, estrogens and the gonadocorticoids)
o The cells in the cortex are stimulated by the anterior pituitary hormone ACTH
(adrenocorticotropic hormone)
o All the cortex hormones are synthesized from cholesterol
 Medulla: innermost “core” of the adrenal gland
o Sympathetic/parasympathetic fibers innervate the medulla
o Tissue embryologically derived from neural crest cells
o Stressors (trauma, hypoxia, hypoglycemia, etc.) trigger the release of
catecholamines (epinephrine and norepinephrine) from the medulla
Hormones of the Adrenal Gland
P715-720
 Cortex Hormones:
o Glucocorticoids (produced in fasciculate layer)
 Metabolic, neurologic, anti-inflammatory and growth-suppressing effects
(or, “steroid hormones that directly effect carbohydrate
metabolism”)
 Three types: hydrocortisone (“cortisol,” most potent, main secretory
product of cortex)), corticosterone & cortisone
 Affects the body in the following ways:
 Promotes normal metabolism, including promoting gluconeogenesis
when blood glucose levels are low or when faced with stress
 Permits sensitivity to changes in blood vessels in reaction to certain
chemicals, and in doing so raises BP (example: sensitizes arterioles
to the vasoconstrictive effects of norepinephrine, a kind of
“permissive affect”)
 Decrease blood vessel dilation and edema associated with
inflammations; can also cause slow wound healing & depressed
immune responses
o Mineralcorticoids (produced in glomerulosa layer)
 Aldosterone is most potent, acts to conserve Na+ by increasing the activity
of the Na+ pump of the epithelial cells (this means cells will retain Na+ and
lose K+ and H+)
 Primarily acts on the kidney’s collecting duct to increase Na+ & H2O
absorption
 How is aldosterone stimulated?
 Low Na+ & H2O or high K+ levels in the blood stimulates renin
secretion
 Renin converts angiotensinogen to angiotensin I
 A conversion enzyme converts angiotensin I to angiotensin II
 Angiotensin II is what stimulates aldosterone release
o Gonadocorticoids (includes estrogens & androgens, produced in reticularis)
 Secretes tiny amounts of sex hormones, effects are insignificant while
ovaries/testes still function
 Medulla Hormones
o Catecholamines (epinephrine & norepinephrine)
 Epinephrine is more potent (10x better at producing direct metabolic
effects than norepinephrine) and medulla production of this hormone is
about 80%, the other 20% is norepinephrine
 Physiologic stress triggers release of these hormones, circulate for only
minutes then rapidly removed
 Effects include hyperglycemia (increase blood sugar levels), increase heart
rate & constrict blood vessels (thereby increase BP), and increase cellular
metabolism
Tests of Endocrine Function
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 Radioimmunoassay (RIA)
o Technique for measuring minute quantities of hormones in the blood
o Antibody that’s specific for the hormone + hormone itself + radiolabeled
hormone all added to one mixture
o Since there isn’t enough antibody to bind with all hormones, the radiolabeled
and non labeled hormones compete for binding sites on antibodies. Counts are
then made
 Enzyme-linked immunosorbent assays (ELISA):
o Similar to RIA but less expensive and easier to conduct
o Instead of radiolabeled hormones, an enzyme-labeled hormone is used
 Bioassay
o Use of graded doses of hormone in a reference preparation and then comparing
those results with results from an unknown, “standard” sample
Thoughts/Theories of Aging on the ES
P720-721
 Relationship btwn aging and ES is unclear: does endocrine function decline because we
age or do we age because our endocrine system starts failing? It’s hard to ID exact
relationship because of age-related variables: actuve/chronic nonendocrine disease, use
of RX, alterations in diet, changes in body composition/weight, changes in sleep-wake
cycles
 Investigation into further understanding the ES system related to aging process has
produced contradictory findings, including:
o Altered biologic activity of hormones (do hormones/receptors work?)
o Altered circulating levels of hormones (kidney is affected)
o Altered secretory response of the endocrine glands (glands are sluggish)
o Altered metabolism of hormones (body can’t break down hormones as quickly)
o Loss of circadian control of hormone secretion (hormones secreted at wrong
time of day)
 Theories of Aging
o Cellular Damage: Suggests adverse cellular conditions produce the biologic
effects associated with aging. The endocrine system is not considered a
causative agent but rather a “victim” of before mentioned “adverse conditions.”
In short, cellular changes may contribute to endocrine gland dysfunction or
alterations in responsiveness of target organs.
 It’s been suggested that loss of self-regulatory patterns of the immune
system may lead to autoimmune phenomenon. These mechanisms may
account for the onset of type II diabetes mellitus (lack of response to
insulin)
o Stress & Adaption: Suggests body structures wear out from over use or are no
longer able to adapt to the cumulative effects of physiologic stress.
 One example may by the sympathoadrenal axis. Exhaustion of this axis
may be associated with an inability of the body to respond effectively to
stressors
o Programmed Changes: Suggests certain secretory cells may be programmed
genetically to secrete hormones for a prescribed length of time. An example of
this might be the female reproduction function.

Any cellular change (whether it’s the 3 theories above or not) affects neuroendocrine
regulation. An impaired hypothalamic feedback system, dysfunctioning regulatory
factors/hormones, altered secretion of neurotrasmitters (affecting hypothalamic &
pituitary functions); there could be many causes of endocrine dysfunction that
contribute to or are associated with aging
How aging affects particular glands
P721-722
 Thyroid:
o Glandular atrophy & fibrosis occur with nodularity & increasing inflammatory
infiltrates (may reflect age-related autoimmune damage)
o Changes relative to T3 and T4 & their functions are hard to assess as both
secretion & turnover rates are reduced
 Pancreas:
o 40/50% of people older than 65 have impaired glucose tolerance or diabetes
o With age, cells are replaced with fat tissue. There is a decrease in insulin
secretion & insulin receptors & irregularities in the responses to insulin are
noted.
o These changes also affect other target orangs, like the cardiovascular system.


Parathyroid:
o There is a calcium imbalance in many older adults and though it hasn’t been
proven, theories suggest this is due to an age0related alteration in PTH
secretion.
o The following changes ARE KNOWN to affect calcium levels on older adults:
 Decrease calcium intake causes a negative calcium balance (usually
because older people are lactose intolerant so don’t get enough calcium)
 Decreased intestinal absorption (they eat the right amounts but intestines
lose absorption power so it doesn’t matter)
 Persistent hypercalciuria indicating defective renal reabsorption (kidneys
aren’t absorbing Ca+)
 Decreased circulating levels of vitamin D3 (found in liver and fish oils)
 Blunted response to PTH
Adrenal:
o Cortex loses weight and has more fibrous tissue after age 50
o In elderly there is a decreased clearance and reduced use of cortisol (due to
decline in liver & kidney function), which means cortisol levels are high in the
body. But the feedback mechanisms are still intact: high cortisol levels decrease
cortisol secretion.
o Plasma levels of adrenal androgens, as well as urinary excretion of the metabolic
end products, decrease gradually but dramatically with age (to as much as
50/70% of the young adult level)