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4) Metabolic Endocrinology > 4) Hypothalamic Axis > Flashcards

4) Hypothalamic Axis Flashcards

1
Q

What was the basis of our thinking about nature until the 18th century?

A
  • Four qualities
  • Four elements
  • Four seasons
  • Four humours
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2
Q

How did Aristotle describe the pituitary gland 2000 years ago?

A

The major connection between the brain and body, through which the four essential humours pass (from brain to body)

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3
Q

What did Rathke describe in the 19th century?

A

The two parts of the pituitary (anterior and posterior)

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4
Q

What did Pierre Marie discover in 1886?

A

The association between pituitary tumours and acromegaly

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5
Q

What did Cushing uncover in 1909?

A
  • Removed part of the pituitary in an acromegaly patient and noticed improvement
  • Pioneered modern neurosurgical techniques
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6
Q

What did Evans and Long show in 1922?

A
  • That injection of crude extracts of the pituitary gland in animals causes increased growth
  • Leads to the discovery of growth hormone
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7
Q

The pituitary is the conductor of the endocrine orchestra. Is this statement true or false?

A

False, as the pituitary is itself controlled by the nervous system via the hypothalamus

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8
Q

How does the size of the pituitary vary during pregnancy?

A

The size increases (by 30%) during pregnancy

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9
Q

What encloses the pituitary gland?

A

Bony matrix (sella turcica of the sphenoid bone)

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10
Q

What nervous structure is situated close to the pituitary, and is affected when the pituitary expands?

A
  • The optic chiasma and optic nerves

- When the pituitary expands, it tends to push on the optic nerves, causing visual-type effects

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11
Q

What is the adenohypophysis?

A

Anterior pituitary

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12
Q

What is the neurohypophysis?

A

Posterior pituitary

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13
Q

Which ectodermal components form the hypothalamo-hypophyseal tract?

A

They are formed of two DIFFERENT ectodermal components

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14
Q

How does the anterior pituitary develop?

A
  • Rathke’s pouch

- The outgrowth of the buccal cavity detaches itself, and becomes the anterior pituitary

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15
Q

The anterior pituitary undergoes (invagination/evagination) during development.

A

Evagination

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16
Q

The posterior pituitary undergoes (invagination/evagination) during development.

A

Invagination

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17
Q

How does the posterior pituitary develop?

A

The infundibulum develops from the outgrowth of the neuroectoderm from the floor of the third ventricle

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18
Q

The outgrowth of the neuroectoderm from the floor of the third ventricle gives rise to which structures?

A
  • Pituitary stalk
  • Median eminence
  • Posterior pituitary
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19
Q

Which ventricle is the posterior pituitary derived from?

A

Third ventricle

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20
Q

Do the anterior and posterior pituitary grow towards or away from each other?

A

They grow towards each other, and at some point they come into contact

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21
Q

What is Rathke’s pouch?

A

Evagination at the roof of the developing mouth, forming the anterior pituitary

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22
Q

How is the hypothalamus organized?

A
  • Into discrete nuclei
  • Producing specific factors to stimulate anterior pituitary, or are associated with the release of hormones from the posterior pituitary
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23
Q

How is the anterior pituitary axis vascularized?

A
  • A capillary bed is contained at the hypothalamus, allowing hormones to be transported to the anterior pituitary (hypophyseal portal system)
  • A capillary bed is contained within the anterior pituitary, allowing the hormone to be secreted into circulation
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24
Q

How may hormones from the anterior pituitary cause a short negative feedback loop on the hypothalamus?

A

They may be retroactively brought back to the hypothalamus

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25
Q

What does the hypothalamus release to the anterior pituitary?

A

Releasing and inhibiting hormones

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26
Q

What does the hypothalamus release to the posterior pituitary?

A

Vasopressin and oxytocin

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27
Q

What nuclei are responsible for the posterior pituitary?

A
  • Paraventricular nucleus

- Supraoptic nucleus

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28
Q

What do neurosecretory neurons from the paraventricular nucleus secrete? Where are the axon termini located?

A
  • Oxytocin (packed into granules)

- Posterior pituitary

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29
Q

What do neurosecretory neurons from the supraoptic nucleus secrete? Where are the axon termini located?

A
  • Vasopressin (packed into granules)

- Posterior pituitary

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30
Q

What is the mechanism of synthesis and release of hormones from the posterior pituitary?

A

1) Hormones are produced in the cell bodies of neurons located in the hypothalamus
2) The hormones are packaged into granules and migrate to the posterior pituitary via their axons
3) Stimulation of neurons in the hypothalamus triggers the release of hormones from the axon tips in the posterior pituitary
4) Hormones are taken up by capillaries and enter the bloodstream

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31
Q

What is the difference between the neurosecretory neurons connected to the anterior and posterior pituitary?

A
  • Releasing hormones are released into a capillary bed, which are transported to the anterior pituitary to stimulate/inhibit hormone release
  • Hypothalamic neurons synthesize hormones, which are stored in the posterior pituitary for release upon stimulation
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32
Q

In terms of the anterior pituitary, axon terminals of hypothalamic neurons release hypophysiotropic hormones in which area?

A

Median eminence

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33
Q

How do hormones released into the capillary bed from the hypothalamus travel to the anterior pituitary?

A

Via the portal vein

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34
Q

The pituitary hormones enter the bloodstream via the _______ capillaries.

A

venous

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35
Q

How were the discrete bundles of nuclei in the hypothalamus discovered?

A

By ablation (destruction of the nuclei)

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36
Q

What was the Halasz knife originally used for?

A

To selectively destroy areas of the brain to observe the function of nuclei (ablation)

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37
Q

What are nuclei?

A

Refers to the cell bodies of the neurons which produce the hypothalamic hormones

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38
Q

What nuclei are responsible for the anterior pituitary?

A

Hypothalamic-hypophysiotropic nuclei

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39
Q

Which areas of the brain does the hypothalamus receive signals from?

A
  • All areas of the brain

- The hypothalamus integrates the information

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40
Q

What does the relay of signals to the hypothalamus involve?

A

Several neurotransmitters

41
Q

What indicates a certain level of autonomy of the anterior pituitary from the hypothalamus?

A

The very low levels of basal GH, FSH, and LH excretion

42
Q

What input signals does the hypothalamus receive and integrate?

A
  • Sleep/wake
  • Pain
  • Emotion, fright, rage, smell
  • Vision
43
Q

What signals does the posterior pituitary regulate?

A
  • Heat regulation (temperature)

- Water balance

44
Q

What signals does the anterior pituitary regulate?

A
  • Metabolic stress
  • Stress response
  • Growth
  • Reproduction
  • Lactation
45
Q

What cells of the anterior pituitary secrete GH?

A

Somatotrophs

46
Q

What cells of the anterior pituitary secrete prolactin?

A

Mammotrophs

47
Q

What cells of the anterior pituitary secrete TSH?

A

Thyrotrophs

48
Q

What cells of the anterior pituitary secrete LH and FSH?

A

Gonadotrophs

49
Q

What cells of the anterior pituitary secrete ACTH?

A

Corticotrophs

50
Q

Which anterior pituitary cells are the most common? Which are the least common?

A
  • Most common: somatotrophs

- Least common: thyrotrophs

51
Q

What are the products of corticotrophs?

A
  • ACTH

- B-lipotropin

52
Q

What are the targets of corticotrophs? (3)

A
  • Adrenal gland
  • Adipocytes
  • Melanocytes
53
Q

What are the products of thyrotrophs?

54
Q

What is the target of thyrotrophs?

A

Thyroid gland

55
Q

What are the products of gonadotrophs?

56
Q

What is the target of gonadotrophs?

57
Q

What is the product of somatotrophs?

58
Q

What are the targets of somatotrophs?

A
  • All tissues

- Liver

59
Q

What is the product of lactotrophs?

60
Q

What are the targets of lactotrophs?

A
  • Breasts

- Gonads

61
Q

Which anterior pituitary cells are basophils?

A
  • Thyrotrophs
  • Gonatotrophs
  • Corticotrophs
62
Q

Which anterior pituitary cells are acidophiles?

A
  • Somatotrophs

- Lactotrophs

63
Q

What is the difference between basophils and acidophils?

A
  • Basophils are heavily glycosylated

- Acidophils are less modified post-translationally

64
Q

What is the major function of TRH?

A

Stimulates the release of TSH and prolactin

65
Q

What is the major function of GnRH?

A

Stimulates the release of LH and FSH

66
Q

What is the major function of GHRH?

A

Stimulates the release of GH

67
Q

What is the major function of somatostatin?

A

Inhibits the release of GH

68
Q

What is the major function of CRH?

A

Stimulates the release of ACTH

69
Q

What is the major function of dopamine, in terms of anterior pituitary hormone release?

A

Inhibits the release of prolactin

70
Q

Describe the half-life and the mechanism of action of hypothalamic hormones affecting the anterior pituitary.

A
  • Short half-life and fast action

- They travel short distances (hypothalamus to the anterior pituitary)

71
Q

How do hypothalamic hormones affect the anterior pituitary, stimulating the release of hormones?

A
  • Hormones bind to receptors of target cells in the anterior pituitary
  • Trigger the release (exocytosis) of stored hormone granules
72
Q

How does post-receptor intracellular signalling occur when hypothalamic hormones affect the anterior pituitary?

A

G-protein intracellular signalling

73
Q

What G-protein subtypes do trophic hormones use? What does that lead to?

A
  • Gas and Gaq proteins

- Leads to increased Ca2+ levels and exocytosis of hormones granules

74
Q

What G-protein subtypes do inhibitory hormones use?

A

Gai and other mechanisms

75
Q

What are two inhibitory hormones secreted by the hypothalamus?

A
  • Somatostatin

- Dopamine

76
Q

What is Tier 1 of the hypothalamic-pituitary axis?

A
  • Hypothalamus

- Hypothalamic hormones

77
Q

What is Tier 2 of the hypothalamic-pituitary axis?

A
  • Pituitary

- Paracrine cytokines and growth factors

78
Q

What is Tier 3 of the hypothalamic-pituitary axis?

A
  • Target gland

- Peripheral hormones

79
Q

What do hypothalamic hormones depend on, due to their short half-life?

A

Renewal of stimulus

80
Q

Describe the release of hypothalamic hormones.

A
  • Release is pulsatile

- The treatment of infertility with GnRH requires administration in pulses with a defined frequency

81
Q

What is the major function of the pineal gland?

A

Integrates information encoded by light into secretions that underlie biological rhythmicity

82
Q

Where is the pineal gland located? What is its shape?

A
  • Located in proximity to the hypothalamus

- Pine cone shaped, about the size of a grain of rice

83
Q

What is the major hormone secreted by the pineal gland?

84
Q

What is melatonin synthesized from?

A

Tryptophan

85
Q

How does melatonin change with age?

A

The absolute concentration of melatonin is highest in children, and decreases with age

86
Q

Describe the circadian rhythm of melatonin secretion.

A
  • The pineal gland begins producing melatonin in the evening
  • Melatonin levels peak in the middle of the night
  • Melatonin levels decline to low daytime amounts in the morning
87
Q

Light is (stimulating/inhibitory) to the formation of melatonin.

A

inhibitory

88
Q

What is the major function of the suprachiasmatic nucleus (SCN)?

A
  • Circadian pacemaker (“clock”)
  • Controls circadian rhythm of many physiological functions, including the pineal gland
  • SCN has melatonin receptors
89
Q

Describe the synthesis of melatonin.

A
  • An electrical transmission stimulates the release of norepinephrine, which binds to B-adrenergic receptors on a pinealocyte
  • Activation of G(alpha)s increases cAMP, resulting in the conversion of tryptophan to melatonin
90
Q

What are other functions of the pineal gland?

A
  • Induction of sleep
  • Depression of reproductive activity (inhibition of ovulation and semen production in some animals)
  • Seasonal fluctuations may affect the timing of breeding, migration, and hibernation in mammals
  • Antioxidant
  • Enhancement of immunity
91
Q

Where are melatonin receptors found?

A
  • Almost everywhere in the human body
  • The functional role of melatonin acting on its receptors in humans remains (except for the circadian and sleep-promoting effects) unclear
92
Q

What are uses for melatonin?

A
  • Adjustment of jet-lag

- Sleeping aid in the elderly

93
Q

What are adverse side effects of melatonin? (5)

A
  • Daytime sleepiness
  • Hypothermia
  • Desensitization of melatonin receptors, if doses too high
  • Possible adverse effects in those with seizure disorders
  • Possible interaction with those taking coumadin/warfarin
94
Q

Self-rated jet lag can be reduced, on average, by __%.

95
Q

What is the basis of chronotherapy?

A

Our bodies respond differently to medications during different times in the day

96
Q

What is chronotherapy used for to maximize effectiveness in relation to biological rhythms?

A

Timing of medication, surgery, and chemotherapy

97
Q

When should asthma medication be taken?

A

Early in the morning

98
Q

When should arthritis medication be taken?

A
  • Late in the day

- Cortisol rises at night, which means that arthritic pain is less bad in the morning

99
Q

When should breast cancer surgery occur?

A
  • After ovulation (luteal phase) when progesterone levels are high, and estrogen levels are low
  • Estrogen is a problem in many types of breast cancer (powerful mitogen)

4) Metabolic Endocrinology (15 decks)

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