Download Endocrine System

ENDOCRINE SYSTEM
Endocrine and Nervous Systems
Two Systems of Control
Hormones: chemical substances produced at one
site which initiates or regulates the activity of an
organ or group of cells in another part of the body.
Neurotransmitters: chemical substances which
modifies or results in the transmission of nerve
impulses at synapses.
7/3/02
Mr. Davenport ©
1
Comparison of Endocrine and
Nervous Systems
• Both systems rely on release of chemicals
– Nervous: synaptic (mostly) and produces a rapid
response
– Endocrine: circulating hormones which may last from a
few minutes to several hours
• Both systems share many chemical messengers
– examples: norepinephrine (NE) and epinephrine (E)
• Both systems respond primarily by negative feedback
• Both systems preserve homeostasis by regulation of
activity of other cells, tissues, organs, and systems
7/3/02
Mr. Davenport ©
2
Overview of Endocrine System
• Endocrine cells (glands) release into interstitial fluid
– may influence local cells (paracrine) or if transmitted through the
blood and lymphatic systems may target at a distance
• Exocrine cells (glands) release their secretion into
ducts.
7/3/02
Mr. Davenport ©
3
HORMONE STRUCTURE
• Classes of hormones
– Amino acid based
• Amino acid derivatives (similar to amino acids)
• Peptide hormones (dipeptide, polypeptide, proteins)
– Lipid based (steroid hormones, derived from
cholesterol, and the eicosanoids, derived from a
fatty acid)
7/3/02
Mr. Davenport ©
4
AMINO ACID DERIVATIVES
• Include:
– three catecholamines• (1) epinephrine (E), from adrenal medullae
• (2) norepineprine (NE), from adrenal medullae
• (3) and dopamine, from hypothalamus
– the thyroid hormones
– and melatonin (from pineal gland)
7/3/02
Mr. Davenport ©
5
Amino Acid Derivative Examples
• Catecholamines are
classified as biogenic
amines (other biogenic
amines include
neurotransmitters, the
indolamines, which
include serotonin (from
trytophan) and histamine
(from histidine)
7/3/02
Mr. Davenport ©
6
Peptide Hormones
(amino acid based)
• hormones which are grouped as (1) peptides
or small proteins and (2) glycoproteins
• their production follows the pattern of
protein synthesis
– DNA -> mRNA -> RER ->modification at ER
or Golgi to produce functional hormone
7/3/02
Mr. Davenport ©
7
Peptide Hormone –
Example
• Insulin is a short
peptide hormone
(other examples include
glucagon, ADH,
oxytocin, calcitonin,
etc.)
7/3/02
Mr. Davenport ©
8
LIPID DERIVATIVES
• Include the steroids and eicosanoids
• Steroids
– Lipids which have the general structure of four hydrocarbon
rings.
– Hormonal steroids produced by the adrenal cortex (cortisol,
mineralocorticoids) and gonads (estrogen, testosterone) are
vital
– Cholesterol is steroid produced by liver and is used in cell
membranes and in the manufacture of steroid hormones
7/3/02
General
structure of steroidMr. Davenport ©
Cholesterol
9
Steroids include:
• Androgens (from testes)
– Testosterone is an
androgen (steroid)
produced by the testes
• Estrogens (from ovaries)
– Estradiol is an estrogen
(steroid) produced by the
ovaries
7/3/02
• Corticosteroids (from
adrenal cortex)
• Calcitriol (from kidney)
Mr. Davenport ©
10
Eicosanoids include:
• Eicosanoids are mostly
local in action
– prostaglandins and
leukotrienes
• Prostaglandin E2
– Prostaglandins are
types of unsaturated
fatty acids which effect
•
•
•
•
Vasomotor tone
Capillary permeability
Platelet aggregation
Smooth muscle
contraction
• ANS
7/3/02
Mr. Davenport ©
11
DISTRIBUTION OF
HORMONES
• Hormones are distributed mostly by
circulatory system (remain functional for a few hours to a
few minutes)
• Inactivated when
– bound to receptors
– broken down by liver or kidneys
– broken down by enzymes in plasma or
interstitial fluid
7/3/02
Mr. Davenport ©
12
HORMONE ACTIONS
• Hormones alter cell activity
– either increase or decrease what the cell normally does
• Actions include changes with influence
–
–
–
–
–
–
permeability of plasma membrane
electrical state (ion channels)
protein synthesis; structural and/or regulatory molecules
enzyme activity: activates or deactivates enzymes
secretory activity
mitotic division
7/3/02
Mr. Davenport ©
13
HORMONE FUNCTION
• The activity of the target cell can be changed by
– Changes in membrane permeability can alter
electrical activity of the cell; functions include nerve conduction, release of neurotransmitter, and
muscle contraction
– A new enzyme or a protein may be produced by
the activation of genes
– The rate of synthesis of enzymes or proteins may
be altered by changing the rate of transcription
– An existing enzyme can be turned “on” or “off”
by a hormone changing the enzyme’s structure
7/3/02
Mr. Davenport ©
14
HORMONES AND RECEPTORS
• Cells must have receptors for the binding of
the hormone; or different receptors for
different hormones
• Receptors are either located on the
– cell membrane or
– intracellular
7/3/02
Mr. Davenport ©
15
HORMONES AND THE CELL MEMBRANE
• Hormones that are not lipid soluble can not enter
the cell; thus, their receptors are located on the cell
membrane.
– These hormones are mostly the amino acid based
hormones and include ACTH, FSH, LH, Glucagon, PTH, TSH,
Calcitonin, Catecholamines)
– Exert influence by a second messenger.
• Hormones that are lipid soluble can enter the cell
membrane; thus, their receptors are located within
the cell.
– These hormones are mostly the steroid based hormones
and involve gene activation/inactivation, enzyme
activation/inactivation, etc.
7/3/02
Mr. Davenport ©
16
HORMONES AND MEMBRANE
PROTEINS
• Hormone acts as a first messenger and results
in the appearance of at least one second
messenger in the cytoplasm.
– Second messenger may function as enzyme
inhibitor, activator, or cofactor. Net result is a
change in the metabolic reactions of the cell
• Amplification - binding of hormone may cause
the release of many second messengers
• Several types of second messengers may be
released in response to one hormone
7/3/02
Mr. Davenport ©
17
Membrane Proteins
• Membrane bound proteins are a link between
the first messenger and the second messenger
• Membrane proteins are activated when the first
messenger (hormone) binds to its receptor and
commonly results in the appearance of the
second messenger.
• Common second messengers are cyclic-AMP
and calcium ions
7/3/02
Mr. Davenport ©
18
1
2
1. Hormone binds to
receptor
2. Receptor binds to
stimulatory protein
(G protein).
3. Stimulatory protein
(G protein)
activates effector
enzyme (adenylate
cyclase)
4. Effector enzyme
(adenylate cyclase)
produces second
messenger, cAMP.
3
4
5
7/3/02
Mr. Davenport ©
19
1
2
3
5. Cyclic AMP is second
messenger and activates
kinases which results in the
activation of cellular
enzymes.
Enzyme activity includes:
1. increase synthesis of proteins,
2. induce secretory activity,
3. open ion channels (change
electrical state/physical state)
4
5
Amplification is due to amount
of cAMP produced
•
7/3/02
Kinase: an enzyme that catalyzes the transfer
of phosphate groups from a high-energy
phosphate-containing molecule (as ATP) to a
substrate
Mr. Davenport ©
20
Inhibition of
Adenylate Cyclase
• Inhibitory G-proteins
lead to reduction of
cyclic AMP
• Reduction of cAMP
(second messenger)
results in enzymes
not be activated (or
inhibited)
7/3/02
Mr. Davenport ©
21
HORMONES AND GENE ACTIVATION
(INTRACELLULAR RECEPTORS)
• Steroid
hormones
diffuse easily
across the cell
membrane
• Activation (or
deactivation) of
genes occurs
which alters
transcription.
7/3/02
Mr. Davenport ©
22
Hormones and Intracellular Receptors (con’t)
– Examples include:
– Testosterone promotes production of enzymes
and structural proteins which promotes
development of skeletal muscle.
– Thyroid hormones bind to mitochondria and
chromatin receptors. Mitochondria binding
increases rate of ATP production and chromatin
receptors alters transcription of enzymes.
7/3/02
Mr. Davenport ©
23
RELEASE OF HORMONES
• Most are controlled by negative feedback
• Most endocrine glands are stimulated to
release their hormones by one of following:
– humoral stimuli
– neural stimuli
– hormonal stimuli
7/3/02
Mr. Davenport ©
24
Humoral Stimuli
• Humoral (fluid) stimuli include blood levels
of ions, nutrients, etc.
– Includes parathyroid hormone (PTH) PTH is
released in response to declining levels of ionic
calcium. Increase levels of ionic calcium
inhibit release of PTH.
– Other examples include insulin (blood sugar)
and aldosterone (sodium ion).
7/3/02
Mr. Davenport ©
25
Neural Stimuli
• ANS (sympathetic) stimulation of adrenal
medulla to release catecholamines
(epinephrine and norepinephrine)
• Also, includes oxytocin and antidiuretic
hormone (ADH).
7/3/02
Mr. Davenport ©
26
Hormonal Stimuli
• Endocrine glands are the target of hormones
released by other endocrine glands.
– Hypothalamus releases releasing and inhibition
hormones which influence the anterior pituitary.
– Anterior pituitary releases hormones which influence
other endocrine glands, such as thyroid stimulating
hormone -TSH. An example of hypothalmicpituitary-target pathway
7/3/02
Mr. Davenport ©
27
Hormonal Stimuli
• Neuroendocrine adjustments
– can be made by the nervous system (such as
hypothalamus and sympathetic system) overriding
the endocrine system.
• Hypothalamus is a “negative feedback” center
concerned with emotions, biological rhythms,
water balance, hunger, temperature, etc.
7/3/02
Mr. Davenport ©
28
PITUITARY GLAND
• Divided into
– anterior lobe
(adenohypophysis)
• largest of two divisions and
is composed mostly of
glandular tissue
•
•
•
•
1 Neurons of Hypothalamus
2 Infundibulum
3 Anterior lobe (adenohypophysis)
4 Posterior lobe (neurohypophysis)
7/3/02
– posterior lobe
(neurohypophysis)
• composed mostly of nerve
fibers from hypothalamus
Mr. Davenport ©
29
Pituitary Gland
• Anterior lobe (adenohypophysis) hormones
include the following:
–
–
–
–
–
–
Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Growth hormone
Prolactin (PRL)
• Of these the first four are called tropic
hormones because they directly influence the
activity of other endocrine glands.
7/3/02
Mr. Davenport ©
30
Hormones of the Anterior Pituitary Gland
7/3/02
•
•
•
•
•
•
TSH; thyroid stimulating hormone
ACTH; adrenocorticotropic hormone
FSH; follicle stimulating hormone
LH; luteinizing hormone
GH; growth hormone
Mr. Davenport ©
PRL; prolactin
31
Thyroid Stimulating Hormone
TSH
• Targets the thyroid
• Stimulates the secretion
of thyroid hormones thyroxine and calcitonin
Thyroxine - effect is
to increase glucose
oxidation and
promote growth
and development
7/3/02
Calcitonin promotes
utilization (storage) of
calcium and calcium
secretion by kidneys if
blood levels are too high
Mr. Davenport ©
32
Adrenocorticotropic Hormone
ACTH
• Targets the adrenal cortex
• Stimulates the secretion of
glucocorticoids.
– Glucocorticoids regulate
cell metabolism, especially
that of glucose.
7/3/02
Mr. Davenport ©
33
Follicle-stimulating Hormone
FSH
• Targets the follicles of
the ovaries
– stimulates follicular
development
7/3/02
• Targets the
sustentacular cells of the
testes
– stimulates the
increased production
of sperm
Mr. Davenport ©
34
Luteinizing hormone
LH
• Targets the “mature follicle”
of ovary
– triggers ovulation
– development of corpus luteum
– secretion of progesterone and
estrogen
• Targets the interstitial cells of
the testes
– secretion of testosterone
7/3/02
Mr. Davenport ©
35
Growth Hormone
GH
• Targets all cells of the
body
– promotes protein synthesis
and mobilization of lipids
7/3/02
Mr. Davenport ©
36
Prolactin
PRL
• Targets the breasts and increases production
of milk
7/3/02
Mr. Davenport ©
37
Endocrine Glands Targeted by
Pituitary Hormones
• Tropic hormones of the pituitary
– Thyroid-stimulating hormone (TSH) targets the
Thyroid Gland
– Adrenocorticotropic hormone (ACTH) targets
the Adrenal Gland (Cortex)
– Follicle-stimulating hormone (FSH) targets
both the ovaries and the testes
– Luteinizing hormone (LH) targets both the
ovaries and the testes
7/3/02
Mr. Davenport ©
38
THYROID GLAND
• Located in anterior neck and
is composed mostly of follicles
and scattered cells called
parafollicular cells
• Hormones include thyroxine
and calcitonin:
– Follicles produce thyroid
hormones (mostly
thyroxine)
– Parafollicular cells
produce thyroid hormone
calcitonin.
7/3/02
Mr. Davenport ©
39
Thyroid Gland
• A follicle consists of a colloid filled cavity which is
surrounded by cuboidal follicular cells
– produce thyroid hormones (mostly thyroxine)
– controlled by TSH (anterior pituitary)
– targets most cells of the body (except brain, spleen, testes, uterus, and
itself)
– effect to increase glucose oxidation and promote growth
and development
• Parafollicular cells are located among the follicles
– produce thyroid hormone calcitonin
– stimulus for secretion is high blood levels of ionic calcium
– targets (1) osteoblasts (deposition of calcium) and (2)
kidneys (secretion in urine)
7/3/02
Mr. Davenport ©
40
Thyroid Gland
7/3/02
Mr. Davenport ©
41
PARATHYROID GLANDS
• Two parathyroid glands located on posterior
surface of each lobe of thyroid
• Endocrine cells are called chief cells
• Produce parathyroid hormone (PTH)
• Stimulus for secretion of PTH is decreased blood
levels of ionic calcium (hypocalcemia)
• Targets
– (1) osteoclasts - remove calcium from bone
– (2) kidneys - reabsorb calcium and conversion of
vitamin D to vitamin D3, calcitriol, which promotes
intestinal absorption
– (3) intestine - promotes absorption of calcium
7/3/02
Mr. Davenport ©
42
Parathyroid Glands
7/3/02
Mr. Davenport ©
43
ADRENAL GLAND
• Located on superior border of each
kidney
• Divided into adrenal cortex (2) and
medulla
Glomerulosa (3), fasiculata (4), reticularis (5)
• Surrounded by a capsule (1)
7/3/02
Mr. Davenport ©
44
Adrenal Cortex
• Adrenal cortex (is divided into three major
regions ) produces three major groups of
hormones
– Mineralocorticoids
– Glucocorticoids
– Gonadocorticoids
7/3/02
Mr. Davenport ©
45
Adrenal Cortex
Mineralocorticoids
• Mineralocorticoids - function in the electrolyte
composition of body fluids.
• Aldosterone is the principal mineralocorticoid; it maintains
sodium balance. Its primary role is the reabsorption of
sodium from the forming urine. Along with sodium water
is reabsorbed (osmotic). Thus, blood pressure and volume
are maintained.
• Secretion is regulated by
• (1) low blood levels of sodium,
• (2) rising levels of potassium
• (3) low blood pressure and/or volume.
7/3/02
Mr. Davenport ©
46
Aldosterone
7/3/02
Mr. Davenport ©
47
Adrenal Cortex
Glucocorticoids
• Glucocorticoids
• regulate cell metabolism, especially that of glucose.
Release regulated by ACTH from anterior pituitary.
• Cortisol (hydrocortisone) is the principal
glucocorticoid.
7/3/02
Mr. Davenport ©
48
Adrenal Cortex
Glucocorticoids
• Effects - Cortisol (hydrocortisone)
– Promotes gluconeogenesis (formation of glucose from
noncarbohydrate sources).
– Mobilizes fatty acids from adipose and promotes their
catabolism as a primary source of energy,
– Promotes the break-down of proteins to conserve available
glucose for the brain.
• Downside of Glucocorticoids
– Stress triggers increase of ACTH and, thus cortisol
production increases. Anti-inflammatory and anti-immune
effects are associated with excess of cortisol.
7/3/02
Mr. Davenport ©
49
Adrenal Cortex
Gonadocorticoids
• Gonadocorticoids include both androgens and
estrogens. Androgens (which include
testosterone) are the primary gonadocorticoids.
• Hormones may be involved in outset of puberty
• Androgens for females are thought to influence sex drive
and may be converted to estrogens after menopause
• Hypersecretion of gonadocorticoids produces
masculinization. At a young age females produce facial
hair, male pattern of hair distribution, and enlarged clitoris.
Males develop early secondary sexual characteristics and an
intense sex drive.
7/3/02
Mr. Davenport ©
50
Adrenal Medulla
• Consists of postganglionic neurons
of the sympathetic nervous system
• Hypothalmic control releases the
hormones (neurohormones)
epinephrine and norepinephrine
into the blood
• Promotes the fight-or-flight
response
7/3/02
Mr. Davenport ©
51
PANCREAS
• Located inferior to
stomach along posterior
wall of abdomen
• Both an endocrine (1%)
and exocrine organ (99%)
• Endocrine
– pancreatic islets
(Islets of
Langerhans)
– produce mostly
insulin and glucagon
7/3/02
• Exocrine
– pancreatic acini are
clusters of pancreatic
cells which produce
pancreatic juice, a
major digestive fluid
Mr. Davenport ©
52
Glucagon and Insulin
• Glucagon promotes hyperglycemia (it produces an increase
in blood sugar)
– promotes breakdown of glycogen into glucose
– promotes neoglucogenesis
– promotes the release of glucose into blood
• Insulin promotes hypoglycemia (it produces a decrease in
blood sugar)
– promotes oxidation of glucose for energy
– promotes the formation of glycogen
– promotes the formation of lipids from glucose
7/3/02
Mr. Davenport ©
53
Hyperglycemia and Hypoglycemia
• Hyperglycemia
– is defined as increased blood sugar (above
normal value)
– Insulin is produced to decrease blood sugar
(hypoglycemic in function)
• Hypoglycemia
– is defined as decreased blood sugar (below
normal value)
– Glucagon is produced to increase blood sugar
(hyperglycemic in function)
7/3/02
Mr. Davenport ©
54
TESTES - FSH and LH
• LH targets the interstitial cells
which produce androgens
• FSH targets the “seminiferous
tubules” which are the sites of
sperm production.
– house sustentacular cells and
spermatogenic cells
7/3/02
Mr. Davenport ©
55
FSH and Spermatogenesis
• FSH targets the sustentacular cells of the
seminiferous tubules which leads to an increase
in spermatogenesis, the production of sperm
7/3/02
Mr. Davenport ©
56
LH and Androgens
• Interstitial cells are targeted by LH
• Interstitial cells (cells of Leydig)
are responsible for the production
of androgens (testosterone and
dihydrotestosterone) – promote development of
secondary sexual characteristics
– increase protein synthesis
– increase sperm production
7/3/02
Mr. Davenport ©
57
OVARY - FSH and LH
• FSH targets “receptive” follicles
and promotes their
development. Developing
follicles produces estrogens.
• LH targets the “mature” follicle
and promotes ovulation and
development of corpus luteum.
7/3/02
Mr. Davenport ©
58
FSH and Follicle Development
• FSH targets “receptive” follicle (#2)
• Estrogens are produced mostly by
developing follicles (#3-4) and by the
corpus luteum (#6).
• Estrogens
– promote development of
secondary sexual characteristics
– target uterus and promote its
development
• Corpus luteum (#6) develops from
ruptured follicle
7/3/02
Mr. Davenport ©
59
LH - Ovulation and
Corpus luteum
• LH
– triggers ovulation
– development of
corpus luteum
– secretion of
progesterone and
estrogen
7/3/02
Mr. Davenport ©
60
THYMUS
• Primary role is the
production of thymic
hormones (thymosin)
which promote the
development of T cells
(lymphocytes)
• Divided into small lobules
which have an outer cortex
and inner medulla.
7/3/02
Mr. Davenport ©
61
T lymphocytes
• T lymphocytes (T cells)
play a role in specific
immunity by direct cell-tocell interaction and the
release of chemical
mediators
– include helper T cells,
cytotoxic T cells, suppressor
T cells, memory T cells, etc.
7/3/02
Mr. Davenport ©
62
KIDNEY
• Produces three major hormones
– erythropoietin
– calcitriol
– renin
7/3/02
Mr. Davenport ©
63
Kidney - Erythropoietin
• Erythropoietin targets bone
marrow to increase
production of RBC.
• Increased RBC production
may be due to hypoxia
– hemorrhagic anemias
(hemolytic or aplastic)
– secondary polycythemia (high
altitude)
– hemorrhage
7/3/02
Mr. Davenport ©
64
Kidney - Calcitriol
• Calcitriol essential for absorption of
calcium and phosphate by digestive tract
– produced in response to PTH
– dependent upon presence of vitamin D3
(cholecalciferol)
– Vitamin D3 is produced by skin and supplied in
the diet.
7/3/02
Mr. Davenport ©
65
Kidney - Renin
• Renin is released in response to decreased
blood pressure and increased sympathetic
(crisis) stimulation of renal nerves.
• Functions as an enzyme which converts
inactive plasma protein, angiotensinogen,
into cascading reactions leading to
production of angiotensin (angiotensin II).
7/3/02
Mr. Davenport ©
66
Kidney : Renin-Angiotensin Pathway
• Primary purpose of the renin-angiotensin
pathway is to increase blood pressure
• Angiotensin
– is a powerful constriction of vascular smooth
muscle (increases peripheral resistance, and
thus blood pressure)
– targets adrenal cortex to increase secretion of
aldosterone. Aldosterone increases sodium ion
reabsorption by the kidneys. Thus, the osmotic
reabsorption of water. Blood volume increases,
thus so does blood pressure.
7/3/02
Mr. Davenport ©
67
Renin – Angiotensin Pathway
7/3/02
Mr. Davenport ©
68
PINEAL GLAND
• Located in brain (part of diencephalon, the roof of
epithalamus.
• Produces melatonin
– Peak production around mid-night produces drowsiness
– Lowest production around noon produces alertness
• Indirectly receives information from optic nerve
• Melatonin influences hypothalamus “biological
clock” region.
7/3/02
Mr. Davenport ©
69
Additional Hormone Producing Organs
• Heart produces atrial natriuretic peptide (ANP)
– Function to decrease blood pressure, blood volume, and
sodium .
• Gastrointestinal tract has enteroendocrine cells
which influence digestive tract activity
• Placenta produces estrogen, progesterone, and
hCG (human chorionic gonadotropin)
• Skin produces cholecalciferol (precursor to
vitamin D)
7/3/02
Mr. Davenport ©
70