1. ENDOCRINE SYSTEM BMS Part II
Prepared and presented by:
Marc Imhotep Cray, M.D.
Drag/Drop Hormone Match ZeroBio
See: IVMS Endo-Endocrine Secretion and Action Part I
2. Target Cell Receptors at Three Locations
Textbook in Medical Physiology And Pathophysiology
Essentials and clinical problems
http://www.zuniv.net/physiology/book/content.htm
2
Section VII: Endocrine Glands
5. Endocrine System Rapid Review
See IVMS Endo-Endocrine Secretion and Action
• Communication system
– Allows for cells in distant parts of body to communicate
– Communication generally slower in onset, but longer in
duration, compared to nervous system communication
• Consists of all the organs that secrete hormones
(endocrine organs)
5
6. Hormones
• Chemical Messengers
• Produced by an endocrine gland
• Released into and carried via bloodstream to target
tissues
– Target tissues = tissue bearing receptors that can bind
and physiologically respond to the chemical messenger
in question
– Amount of chemical messenger produced and released
into circulation is generally very small
6
7. Peptide Hormones
• Majority of hormones are proteins/peptides
• Preprohormones prohormones active
• form
• Bind to receptors located on the plasma
membrane (surface receptors)
• Responses generally occur very rapidly and are
short-lived, compared to steroid hormone
responses
7
8. Cell Surface Receptors
1. G-protein coupled receptors
2. Enzyme receptors
3. Receptors associated with ion channels
8
9. G-Protein Coupled Receptors
Animation: G-protein Signal Transduction at Texas A&M
• Hormone binds to extracellular site on receptor
• On cytoplasmic side, receptor is associated with
inhibitory or stimulatory G-Proteins (guanine-
binding)
• Hormone binding on extracellular side activates
intracellular G-proteins
• Activated G-Proteins interacts with effector
proteins (ion channels and enzymes) to elicit
physiological response
9
11. Enzyme Receptors
• Hormone binds to extracellular portion of
receptor
• Site on cytoplasmic portion of receptor has
enzymatic activity that is activated by hormone
binding on the extracellular side
• Altered enzyme activity leads to chain of
reactions that produce physiological response
11
13. Receptors Possessing Ion Channels
• Hormone binds to site on extracellular part
of receptor
• Receptor itself also functions as ion channel
• Binding of hormone to extracellular portion
of the receptor causes change in shape of
receptor that alters open/closed ion
channel status
13
15. Steroid Hormones
• Modified Cholesterol Derivatives
– Cholesterol = precursor for their production
– Have fused ring structures
• Are lipid soluble
– Readily dissolve in and pass through plasma
membrane
– Bind to cytoplasmic or nuclear receptors
• Alter gene transcription/protein production
• Physiologic effects occur more slowly but last longer
than peptide hormone responses
15
16. Steroid Hormone Production
• Adrenal glands: aldosterone, cortisol,
and androgens
• Kidneys: 1,25-dihydroxyvitamin D3
• Gonads
– Ovaries: progesterone and estrogens
– Testes: androgens (testosterone)
See Animation: Biochemistry of Cholesterol by Rodney F. Boyer
16
17. Amine Hormones
• Amino acid (tyrosine) derivatives
• Includes:
– T3 (triiodothyronine)and T4 (thyroxine) =
thyroid hormones
– Catecholamines
• Epinephrine & norepinephrine = adrenal (medulla)
hormones important in stress response
• Dopamine (hypothalamic hormone)
Animation: Adrenaline Action University of Washington
17
18. Neurons vs Endocrine Cells
Neurons Endocrine Cells
• Respond to environ- • Respond to environ-
mental changes by mental changes by
production and production of
transmission of electrical hormones
signals
• Stimulate effector cells
• stimulate effector cells via hormone release
via NT release into the into the bloodstream
synapse
18
19. Neuroendocrine Cells
• Cells with properties of both neurons
and endocrine cells
• Specialized neurons that, when
stimulated, produce chemical
messengers (hormones) that are
released into the circulatory system
• Represent the site of functional overlap
of the neural and endocrine system
19
20. Coitus-Induced Ovulation
• Neuroendocrine Reflex
• Occurs in rabbits, cats, ferrets, camel, llama
• Ovulation is triggered by mating - does not
occur in the absence of mating
• Neural signals initiated by mating alter
reproductive hormones to trigger ovulation
20
21. Prolactin and Oxytocin
• Prolactin = hormone from the anterior
pituitary that plays a role in milk formation
• Oxytocin = hormone from the posterior
pituitary that plays a role in milk release
and uterine contraction
21
22. Milk Let-Down Reflex
• Suckling of newborn produces neural signals that
stimulate neurons in hypothalamus to secrete
oxytocin
• Oxytocin produces contraction of smooth muscle in
the mammary glands the moves milk through ducts
and expels it from the nipple, thus promotes milk
release
• Mental stimuli can also produce neural signals that
cause same response
– Lactating women can experience milk let-down in
response to crying baby
22
24. Hypothalamic-Pituitary Axis
• Hypothalamus
– Region of brain (diencephalon)
– Lies below third ventricle at base of brain
– Important regulator of endocrine action
• Pituitary Gland (hypophysis)
– Endocrine gland connected to hypothalamus
by infundibulum (stalk containing nerves and
small blood vessels)
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26. Hypothalamus
• Contains neuroendocrine cells
• Contains neuroendocrine whose
cells that release – cell bodies lie within
neurohormones which hypothalamus
• Hypothalamus = site of hormone
1. enter the portal vessels production
and are transported to
– axons travel through
anterior pituitary
hypothalamic-pituitary stalk
2. regulate anterior and terminate in posterior
pituitary hormone pituitary
production • Posterior pituitary = site of hormone
storage and release
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27. Pituitary Gland
• In humans has two lobes = distinct glands
– Anterior (toward front of head) lobe =
adenohypophysis
– Posterior (toward back of head) lobe =
neurohypophysis
• Lobes connected to hypothalamus by different
means
– Anterior lobe connected by (portal) blood vessels
– Posterior lobe connected by nerves (axons)
27
28. Textbook in Medical Physiology And Pathophysiology
Essentials and clinical problems
http://www.zuniv.net/physiology/book/content.htm
Section VII: Endocrine Glands 28
30. Posterior Pituitary
• Outgrowth of the hypothalamus; composed of
neural tissue
• Specific neuroendocrine cells in hypothalamus
have axons that project through the stalk and
into the posterior pituitary
• Secretes two important hormones
– Oxytocin (OXY)
– Antidiuretic hormone (ADH)
30
31. Oxytocin and ADH: Production and
Release
• Produced in cell bodies in hypothalamus
• Stored in and released from axon terminals in the
posterior pituitary
• Both hormones are also produced in other brain
areas and function in brain as
neurotransmitters/neuromodulators
31
33. OXY and ADH Action
• Oxytocin
– Acts on smooth muscle in the uterus and
breast
– Produces contractions that result in
parturition and milk let-down
• ADH
– Acts in kidney to regulate water balance and
control blood pressure
33
38. Hypothalamic Releasing
Hormones
• Produced in and released from hypothalamus
• Enter portal blood vessels and are transported to
ANTERIOR PITUITARY
• Stimulate discrete cell types within anterior
pituitary to secrete additional hormone(s)
38
39. Hypothalamic Releasing Hormones
• Corticotropin Releasing Hormone (CRH)
– Acts on corticotrophs
– Stimulates AP production of adrenocorticotropic
hormone (ACTH)
• Thyrotropin Releasing Hormone (TRH)
– Acts on thyrotrophs
– Stimulates AP production of Thyroid Stimulating
Hormone (TSH)
39
40. Hypothalamic ‘Releasing’ Hormones
• Gonadotropin Releasing Hormone (GnRH)
– Previously known as Luteinizing Hormone
Releasing Hormone (LHRH)
– Acts on lactotrophs to stimulate AP production of
Follicle-Stimulating Hormone (FSH) and Luteinizing
Hormone (LH)
40
41. Hypothalamic Releasing
& Inhibitory Hormones
• Growth Hormone Releasing Hormone (GHRH =
somatotropin)
– Acts on somatotrophs
– Stimulates AP production of Growth Hormone (GH)
• Growth Hormone Inhibitory Hormone (GIH =
somatostatin)
– Acts on somatotrophs
– Inhibits AP production of Growth Hormone
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42. Hypothalamic Dopamine
Production/Release
• Distinct dopamine-secreting neurons in
hypothalamus
• Dopamine enters portal vessels and is transported to
Anterior Pituitary
• Acts on lactotrophs to INHIBIT AP production of
Prolactin
42
43. PRL vs Other AP Hormones
• With the exception of PRL, other AP hormones are
not secreted unless stimulated by ‘releasing’
hormones from hypothalamus
• PRL is continuously produced/secreted unless
inhibited by hypothalamic dopamine
43
44. HYPOTHALAMUS SUMMARY
TRH GnRH DA OXY
CRH GHRH/GHIH ADH
+ + + + - -
TSH FSH/LH PRL OXY
ADH
ACTH GH
+ + +
+
Breast +
Thyroid Ovary/Testes
+ Breast
All Tissues +
Adrenal Cortex
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45. Thyroid Gland
• Located in the neck; in front and on either side of
trachea
• Secretes two hormones
– T3 = triiodothyronine
– T4 = thyroxine Modified tyrosine
• T4 secretion > T3 secretion molecules
• T4 converted to T3 in most tissues, especially liver
and kidney
• T3 is more active hormone than T4
45
46. Thyroid Hormones
• Require iodine for synthesis
– Iodine absorbed in GI tract by active transport;
converted to iodide in process
– Iodide is taken up by thyroid gland, by active
transport process, and converted back to iodine
• Iodine is incorporated into T3 and T4
46
47. Thyroid Hormones
• Stimulate growth and metabolism
• Function in fetal/early postnatal brain
development
– Iodine deficiency that results in maternal or fetal
thyroid hormone deficiency can result in severe
mental retardation
• Functions in adult brain function
47
48. Diseases of Thyroid Gland
With eMedicine Article links:
• Hypothyroidism = underactive thyroid
– Slowed metabolic rate, fatigue, weight gain
– Cretinism, if present and untreated at birth
• Hyperthyroidism = overactive thyroid
– Increased metabolic rate
– Enlargement of thyroid gland (goiter)
– Weight loss, nervousness, irritability
– Intolerance to heat
– Bulging eyeballs
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49. Adrenal Glands
With eMedicine Article links:
• Paired glands; located on top of kidneys
• Each adrenal gland has two parts
– Medulla
• Inner portion
• Synthesizes/secretes epinephrine and norepinephrine
(stress hormones)
• Pheochromocytoma
– Cortex
• Outer portion
• Secretes steroid hormones
• Cushing Syndrome
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55. Plasma Constituent
• PTH production by parathyroid glands
• PTH regulates serum calcium and phosphate
levels
• PTH secretion is regulated by serum calcium
levels
– Increased serum calcium inhibitis PTH secretion
– Decreased serum calcium stimulates PTH secretion
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56. PTH Target Tissues
• Bone
– Increases bone resorption; moves calcium and
phosphate from bones into extracellular fluid
• Kidney
– Stimulates activation of Vitamin D (converts
25(OH)vitamin D to 1,25-dihyrdoxyvitamin D
– Increases tubular calcium reabsorption; decreases
tubular phosphate reabsorption
• Intestine
– Activated Vit D increases intestinal absorption of
calcium
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58. Hormonogen Regulation
• Hormonogen = (inactive) hormone precursor
participates in physiological response to
environmental changes
• Example: Aldosterone production by adrenal cortex
• Hormone secreted into plasma acts on hormonogen
and converts it to active hormone
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59. Aldosterone
• Steroid hormone from adrenal cortex
• Regulates ion balance
– Target tissue = collecting ducts in nephrons of
kidney
– Stimulates reabsorption of Na+ from ultrafiltrate
back into bloodstream
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60. Aldosterone Regulation
• Angiotensinogen = hormonogen secreted into
blood by liver
• Angiotensinogen is converted to Angiotensin by
Renin
– Angiotensin = active form of hormone
• Stimulates adrenal cortex to produce/release
aldosterone
– Renin = kidney hormone produced in response to
drop in blood pressure or blood volume
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62. Ingestion or
Biosynthesis of Precursor
• 1,25-dihydroxyvitamin D3 production
– Vitamin D3 ingested in diet or synthesized in skin
• in skin, ultraviolet radiation converts cholesterol derivative to Vit D3
• Subsequently modified by hydroxylations in liver and kidney
– Main action of 1,25-dihydroxyvitamin D3 is to stimulate intestinal Ca++
absorption
• Thyroid hormones
– Tyrosine (amino acid) ingested or produced by interconversion of other
amino acids
– Modified by iodinations
– T3 and T4 regulate metabolism and affect brain development/function
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63. Hormone Production Regulation
Hypothalamic-Pituitary Control; negative
feedback loops
– Hormone produced by the terminal endocrine
gland in an endocrine axis feeds back at the level
of the hypothalamus and/or pituitary to ultimately
inhibit its own production
– Examples:
• TH in thyroid
• Cortisol in adrenal cortex
63
64. Endocrine System and Aging
• Endocrine glands decrease in size with aging
• Hormonal profile changes with aging
– Generally hormone concentrations decrease with aging
– Some hormone concentrations increase with aging
• e.g. adrenal glucocorticoids (cortisol/corticosterone) which,
in higher concentrations, over time, damage brain/neural
tissues
• Receptor numbers and/or receptor responsiveness are altered with
aging
• Collectively, these changes decrease organisms ability to respond
to environmental changes and cope with stress
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65. Anabolic Steroids
• Synthetic testosterone
• Clinically used to promote anabolic effects (growth)
– Estrogen and Testosterone promote GH and IGF-I
secretion that results in prepubertal growth spurt and
induces closure of the bone growth plate at puberty
– Testosterone (but not estrogen) has anabolic effect on
protein synthesis that produces increased muscle mass
• Abused by athletes in an attempt to gain muscle
mass and increased strength
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66. Negative Side Effects of Anabolic
Steroids
In men In women
– Decreased plasma – Virilization
testosterone • deepened voice
– Sterility • hirsutism
– Testicular atrophy – Alopecia (hair loss)
– Gynecomastia – Acne
Both sexes
–Hypertension and cardiovascular disease
–Liver tumors
–AIDS (via sharing needles for injection)
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67. End of Session
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