Endo-Endocrine Secretion and Action II

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

3. SIGNAL TRANSDUCTION
See: G-protein Signal Transduction
3

4. EXAMPLE: subdivisions of the adrenal gland
4

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

10. G-Protein Coupled Receptors
10

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

12. Enzyme Receptors
(animation)
12

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

14. Receptors Possessing Ion Channels
14

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

23. Links to the individual hormones
23

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)
24

25. Animation :Thyroid Gland Functioning by Leif Saul
25

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
26

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

29. Pituitary Gland
29

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

32. 32

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

34. RENIN-ANGIOTENSIN-ALDOSTERONE AXIS
34

35. 35

36. Anterior Pituitary
• Endocrine (hormone-secreting) gland containing
several different cells types
– Lactotrophs; secrete prolactin
– Gonadotrophs; secrete LH and FSH
– Somatotrophs; secrete Growth hormone
– Thyrotrophs; secrete Thyroid stimulating hormone
– Corticotrophs; secrete Adrenocorticotropic Hormone
• Connected to hypothalamus by portal blood vessels
36

37. Hypothalamus
Hypophysiotrophic Hormones
Inhibitory Hormones
(Stimulatory ‘Releasing’ Hormones)
Anterior Pituitary
ACTH, GH, PRL, TSH,
FSH, LH,
Endocrine Gland
37

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
41

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
44

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
48

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
49

50. Adrenal Cortex Steroid Hormones
• Cortisol and Corticosterone
– Regulate metabolism during fasting
– Glucocorticoids
• Aldosterone
– Regulates Na+ and K+ balance; promotes Na+ reuptake
in kidney
– Mineralocorticoid
– Hyperaldosteronism, Primary
• Dehydroepiandrosterone
– Androgen (testosterone precursor)
50

51. Diseases of Adrenal Glands
With eMedicine article links:
• Cushing’s Disease
– hyperactive adrenal cortex
– rounded face & obesity
– Thin, frail skin poor wound healing
– Hirtsuism (excess hair growth) in females
• Addison’s Disease = adrenal cortex insufficiency
– Decreased appetite, weight loss
– Cold intolerance
– Stress susceptibility
51

52. Parathyroid Glands
• Located within thyroid gland
• Secrete parathyroid hormone (PTH)
– regulates plasma Ca++ and PO3++ levels
– requires Vitamin D3 as cofactor
• PTH excess bone demineralization
• PTH insufficiency abnormal muscle
contraction (tetany)
eMedicine Articles:
Hyperparathyroidism
Hypoparathyroidism
52

53. Hormone Production Regulation
1. Neural control
– Hypothalamic releasing hormones
2. Plasma Constituent
– PTH; regulated by serum Ca++ levels
– Insulin; regulated by serum glucose levels
3. Hormonogen (hormone precursor)
– Aldosterone; regulated by angiotensin levels
53

54. Hormone Production Regulation
• Ingestion or biosynthesis of precursor
• Hypothalamic-Pituitary Control
54

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
55

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
56

57. PTH Regulation
Intestine Kidney Bone
+ + + Serum Ca++
Serum Ca++
+ Parathyroid Glands
57

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
58

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
59

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
60

61. +
Kidney
Liver Aldosterone
Renin
+
Adrenal
Angiotensinogen Angiotensin
Cortex
61

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
62

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
64

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
65

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)
66

67. End of Session
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67