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+ BIOL 371 > Lecture 17: Neuroendocrinology – Brain to Hormones > Flashcards

Lecture 17: Neuroendocrinology – Brain to Hormones Flashcards

1
Q

What is a hormone?

A

any chemical that acts as a physiological signal AND is transported through the bloodstream

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2
Q

What is a neurohormone?

A

hormone produced and released by neuroendocrine cells into blood that signals throughout the body (anterograde neuroendocrine signals)

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3
Q

What is an endocrine organ?

A

structure that produces hormones

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4
Q

What is an endocrine cell?

A

structure that produces hormones

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5
Q

There are many different endocrine organs/organs that contain endocrine cells in our body. What are they controlled by?

A

most operate at least semi-independently

but some are quite directly controlled by neuroendocrine cells

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6
Q

What are anterograde neuroendocrine systems?

A

where neurons release hormones

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7
Q

What are 4 anterograde neuroendocrine systems?

A
  • pineal gland
  • hypothalamus
  • hypophysis/pituitary gland
  • medulla of adrenal gland
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8
Q

What hormone does the pineal gland release?

A

melatonin

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9
Q

What hormone does the hypothalamus release?

A

pituitary releasing hormones

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10
Q

What hormone does the hypophysis/pituitary gland release?

A

posterior pituitary hormones

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11
Q

What hormone does the medulla of the adrenal gland release?

A

epinephrine/adrenaline

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12
Q

What is the adrenal gland?

A

multi-layered structure that has two endocrine organs in one

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13
Q

What are the two layers of the adrenal gland?

A

cortex – outer layer

medulla – inner layer

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14
Q

What does the adrenal cortex do?

A

secrete multiple steroid hormones

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15
Q

What does the adrenal medulla contain?

A

chromaffin cells

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16
Q

What are chromaffin cells?

A

modified postganglionic sympathetic neurons that lack axons, dendrites, or neuron-like electrical responses

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17
Q

What is the function of chromaffin cells (which are in the adrenal medulla)?

A

secrete norepinephrine (NE) and epinephrine (E) into bloodstream via specialized large vesicles

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18
Q

What neurons target adrenal glands?

A

sympathetic preganglionic neurons – stimulate chromatin cells to release epinephrine (adrenaline) (80%) and norepinephrine (noradrenaline) (20%) into bloodstream

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19
Q

What type of receptors does epinephrine have? What is it used as?

A

metabotropic receptors, used as both hormone and neurotransmitter

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20
Q

How does epinephrine know whether to act as hormone or neurotransmitter?

A

sub-type of adrenergic receptor present on smooth muscle cells – differs depending on what part of the body they are located in

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21
Q

Adrenergic Receptor – Alpha 1 Subtype

  • expressed by
  • activation causes
  • cascade type
A
  • expressed by blood vessel smooth muscle in skin and visceral organs
  • activation causes vasoconstriction
  • G αq cascade
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22
Q

Adrenergic Receptor – Beta 2 Subtype

  • expressed by
  • activation causes
  • cascade type
A
  • expressed by blood vessel and bronchiole smooth muscle and cardiac myocytes
  • activation causes reduced contractions (dilation) in smooth muscle
  • activation causes enhanced contractions in cardiac muscle
  • G αs cascade
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23
Q

How does a G αs cascade lead to muscle relaxation?

A

there are PKA- and PKA-activated kinases in these smooth muscles which lead to inhibition of contractile pathways when active

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24
Q

What is the hypothalamus?

A

cluster of nuclei (collections of associated neurons) located at base of forebrain, just above optic chiasm

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25
Q

What does the hypothalamus have control over?

A

almost every behaviour and non-behavioural physiological response vertebrates can make

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26
Q

What are the complex circuits of the hypothalamus?

A

complex circuits include: afferent neurons, interneurons, and efferent neurons

  • widespread divergence and convergence of interneurons
  • hypothalamic nuclei contain sensory neurons and effector neurons as well as interneurons
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27
Q

What do hypothalamic effector neurons act as?

A

act as neuroendocrine cells – secrete their neurotransmitter/hormones into bloodstream through pituitary gland (hypophysis)

do NOT synapse onto muscle cells

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28
Q

What are the two divisions of the pituitary gland (hypophysis)? How do they differ?

A

anterior and posterior – which are connected to different hypothalamic nuclei

the two systems of neuroendocrine cells secrete different hormones into blood through distinct networks of blood vessels

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29
Q

What does the posterior pituitary (neurohypophysis) contain?

A

axons that release neuropeptide hormones

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30
Q

Two of the hypothalamic nuclei (PVN and SON) contain neurons that release what?

A

either of two small peptides known as nonapeptides (vasopressin and oxytocin)

  • nonapeptide is released as neuromodulator within CNS, OR are neuroendocrine effector cells
  • the cells project their axons through the pituitary stalk (infundibulum) into the posterior pituitary where their axon terminals synapse onto blood vessels
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31
Q

What are nonapeptides?

A

small proteins released from axon terminals via specialized vesicles

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32
Q

What are the two types of nonapeptides? How are the similar and different?

A

vasopressin and oxytocin

synthesized from different genes, but their sequences are highly similar (and both have 9 amino acids each)

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33
Q

How are nonapeptides synthesized?

A
  • (like any messenger peptide) synthesized as larger, inactive proteins on ribosome, then packaged into special dense core vesicles
  • inside DCVs, pro-peptide is cleaved into final peptide
  • final peptide is secreted via axon terminals, within brain or into blood via posterior pituitary
34
Q

Vasopressin – Hormone

What is vasopressin called when it is acting as a hormone?

A

antidiuretic hormone (ADH)

35
Q

Vasopressin – Hormone

Where are the receptors?

A

main receptors are in kidneys

36
Q

Vasopressin – Hormone

What does it do?

A

acts to promote water retention – decreases urine production, and therefore decreases blood osmolarity

37
Q

Vasopressin – Neuromodulator

Where is it released from?

A

axons inside the brain

38
Q

Vasopressin – Neuromodulator

What is its function?

A

associated with neural circuits in brain that control sexual activity, aggression, and territoriality

39
Q

As a peptide, does vasopressin cross the BBB easily? What are the consequences of this?

A

no – this means that the same molecule is able to be used in very different roles OUTSIDE (hormone) and INSIDE (neurotransmitter/neuromodulator) the CNS without having to worry about crosstalk when the molecule is released for one function

40
Q

How do neural circuits regulate and control the secretion of neuroendocrine hormones?

Steps

A
  1. in several regions of the hypothalamus, BBB is somewhat leaky, allowing blood plasma to enter brain tissue
  2. a) sensory neurons in vascular organ of lamina terminalis (OVLT) have a variety of sensor proteins that detect plasma composition
  3. b) vasopressin (VP)-secreting neurons also have osmosensing receptors – activate in response to hypertonic solutions
  4. if blood plasma becomes hypertonic (by dehydration), this is sensed by osmoreceptor proteins on OVLT and VP neurons – neurons depolarize, increasing their AP firing
  5. receptor potential + EPSPs in VP neurons enhance release of vasopressin through axon terminals in posterior pituitary gland into bloodstream
  6. vasopressin acts on its receptors in kidneys, helping to conserve water, and therefore restore plasma osmolarity to stop activation of osmoreceptors
41
Q

Oxytocin – Hormone

Where are the receptors?

A

in smooth muscle of mammary glands and uterus

42
Q

Oxytocin – Hormone

What is its functions?

A

acts (via Gαq-coupled GPCRs) to promote smooth muscle contractions in smooth muscle of mammary glands and uterus

43
Q

Oxytocin – Neuromodulator

Where is it released?

A

inside brain (like vasopressin)

44
Q

Oxytocin – Neuromodulator

What is its function?

A

its CNS actions (via the same GPCR) are linked to maternal behaviour, social behaviour, and in some species sexual and pair bonding behaviours

also thought to have general anti-anxiety effects

45
Q

Where do oxytocin (OT)-releasing neurons also send axons?

A

to the posterior pituitary, releasing the peptide as a neurohormone AND being used inside CNS as neuromodulator

46
Q

Primary Data Slide – Female Mice Without Oxytocin (OXT gene)

A

can give birth – but can’t suckle

  • have normal pregnancies, and (somewhat surprisingly) give birth normally (after the same amount of time and at the same rate (number of pups and litters) as wild type mice)
  • their offspring die rapidly unless they are cross-fostered to WT mice because the dams’ teats make milk, but fail to eject it
  • giving the dam (parent) oxytocin injections restores the pups’ feeding and survival
  • oxytocin receptors (OTRs) are present in high density in myoepithelial cells of mammary glands in actively lactating animals
    conclusion: basic physiological role of oxytocin conserved in mammals is milk letdown (ejection)
47
Q

Primary Data Slide – Oxytocin and Auditory Stimulation

A

oxytocin is released into the blood after auditory stimulation – it can evoke an effect on a target organ (milk ducts) that does not contain motor neurons because milk letdown is triggered by oxytocin (neurohormone)

  • oxytocin levels in the blood of lactating people rise within ~2 minutes of baby crying (this occurs before the baby begins to suck)
  • prolactin (hormone which stimulates milk production) is not released by auditory stimulation, but its levels do increase after suckling
48
Q

What is the anterior pituitary (adenohypophysis)?

A

endocrine organ that responds to hypothalamic releasing hormones

49
Q

Is the anterior pituitary (adenohypophysis) part of the nervous system?

A

technically no – because it develops from the roof of the mouth

50
Q

How does the hypothalamus supply neurohormones to the anterior pituitary?

A

neurons in hypothalamus (different ones from those that project to the posterior pituitary) secrete neurohormones into blood vessels at the median eminence

these blood vessels form a special portal vein system that supplies blood to only the anterior pituitary

51
Q

What are hypothalamic releasing hormones? What is their function?

A

neurohormones released by hypothalamic neurons into median eminence

trigger (or inhibit) release of other hormones by anterior pituitary cells which enter the general bloodstream

52
Q

Tumours located where can cause endocrine symptoms?

A

tumours that put pressure on the pituitary gland and portal veins

53
Q

Why do tumours on the optic nerve cause non-neurological symptoms?

A

optic nerve enters the brain at the optic chiasm, directly anterior to the median eminence

54
Q

Pressure on the area around the optic chiasm can affect neuroendocrine circuits in both parts of pituitary gland. How?

A
  • pressure-induced activation of neuroendocrine cell APs = hypersecretion of releasing hormones or posterior pituitary hormones
  • compression of blood posterior pituitary hormones vessels within the portal system prevents transport of releasing hormones into the anterior pituitary = hypersecretion or hyposecretion of anterior pituitary hormone
55
Q

What is the release of anterior pituitary hormones controlled by?

A

hypothalamus

56
Q

What do anterior pituitary hormones stimulate?

A

typically stimulate the secretion of other hormones from endocrine organs elsewhere in the body

57
Q

What are axes?

A

three-hormone releasing sequences through the anterior pituitary

  • releasing hormone
  • pituitary hormone
  • effector hormone
58
Q

What are releasing hormones?

A

neurohormones that stimulate (or inhibit) the release of pituitary hormones

ie. CRH, TRH + SST, GnRH, dopamine (PrIH), GHRH + SST (GHIH)

59
Q

What are pituitary hormones?

A

hormones released from anterior pituitary that stimulate the release of effector hormones

ie. ACTH, TSH, LH + FSH, prolactin (PRL) – acts like an effector hormone (directly on its target organ), GH

60
Q

What are effector hormones?

A

hormones that have a variety of effects on many end organs (and inhibit further release of both releasing hormones and pituitary hormones)

ie. cortisol/corticosterone, T4/T3 , testosterone/inhibin, estrogen/progesterone/inhibin, IGF-1

61
Q

What is the original form of combined oral contraceptive pills (birth control pill)?

A

series of small doses (vary over a 28 day cycle) of an estrogen and a progestogen (synthetic versions of ovarian steroid hormones)

62
Q

How do combined oral contraceptive pills (birth control pills) work?

A

prevent ovulation from occurring

mechanism can initially seem counterintuitive because endogenous estrogens, in particular, are necessary for ovulation to occur

63
Q

What are hypothalamic-pituitary-effector hormone systems?

A

xes that form negative feedback loops

64
Q

Hypothalamic-Pituitary-Gonadal (HPG) Axis

Where are the receptors for gonadal steroids (ie. androgen receptor, estrogen receptors)?

A
  • hypothalamic neurons that release GnRH

- anterior pituitary gonadotrophs (gonadotropin-secreting cells)

65
Q

Hypothalamic-Pituitary-Gonadal (HPG) Axis

What happens when gonadal steroids bind to their receptors?

A

inhibit release of both GnRH and gonadotropins

66
Q

Oral Contraceptive Mechanism

How do these pills work?

A

by blocking surges in GnRH and gonadotropin secretion

67
Q

Oral Contraceptive Mechanism

What is GnRH? Where and when are they released?

A

peptide neurohormone (like oxytocin or vasopressin)

released from DCVs in GnRH-secreting neurons whenever they go through pulses – cyclic periods of intense bursting of AP firing

68
Q

Oral Contraceptive Mechanism

What does an increase in GnRH neuron pulse frequencies (triggered by changes in activity of interneurons that synapse on GnRH neurons) lead to?

A

surge in LH and FSH secretion, which triggers ovulation

69
Q

Oral Contraceptive Mechanism

What inhibits the activity of GnRH neurons (and/or the interneurons that synapse on them)?

A

low levels of progesterone and/or estrogen acting through steroid receptors in GnRH neurons

  • GnRH neurons will be unable to build up to the high activity needed for a strong surge in secretion (which is needed to release LH from anterior pituitary)
  • gonadotropin (LH) levels in blood will not reach the level required to trigger ovulation
70
Q

Hypothalamic-Pituitary-Adrenal (HPA) Axis

What is this axis involved in?

A

regulating the response to stressful situations

71
Q

Hypothalamic-Pituitary-Adrenal (HPA) Axis

What are some of the short-term responses?

A
  • secretion of glucocorticoids helps mobilize energy stores – ie. help supply muscles with glucose for exertion
  • because of negative feedback of cortisol on H and P, this is a self-limiting response
72
Q

What are some properties of steroid hormones?

A
  • derived from cholesterol

- hydrophobic, which means they are lipid soluble – can easily cross the blood-brain barrier (BBB)

73
Q

What types of hormones are the effector hormones for both the HPA and HPG axes?

A

steroid hormones

74
Q

How can negative feedback be altered?

A

by chronic elevations of the effector hormone

because cortisol and other glucocorticoids (steroid hormones) can cross BBB, they can access neurons throughout the brain

75
Q

What does the hippocampus negatively regulate?

A

CRH cells in hypothalamus (except during chronic stress)

  • loss in excitability isn’t great for hippocampal functions (ie. LTP and/or memory formation)
  • some hippocampus neurons also project to hypothalamus, where they make excitatory synapses with circuits that inhibit the activity of CRH releasing cells in the PVN (hypothalamus) – reduction in hippocampal excitability from prolonged cortisol exposure will disinhibit CRH releasing neurons, compared to baseline, which enhances ACTH release, which enhances cortisol release, which amplifies reduction in hippocampal cell excitability (positive feedback)
76
Q

What receptors do many hormones act through? What does this mean?

A

membrane-bound metabotropic receptors – this means that they can have different effects on target organs depending on receptor type

77
Q

What is the release of posterior pituitary hormones regulated by?

A

sensory circuits, which can be either totally within the hypothalamus or relayed to it – leads to excitation or inhibition of hormone releasing neurons, and thus changes in their secretion

78
Q

What is the release of anterior pituitary hormones regulated by?

A

hypothalamus – regulation is more complex

  • brain circuits sense and direct hormonal release
  • negative feedback loops – where effector hormones released by the action of anterior pituitary hormones inhibit the release of their releasing hormones
79
Q

What is the source of the majority of neurohormones?

A

hypothalamus

contains sensory neurons, interneurons, and effector neurons, and its hormonal outputs (mostly through the two parts of the pituitary gland) act in parallel with its neural outputs through the brainstem and spinal cord to coordinate physiology and behaviour

80
Q

Are NE (norepinephrine) and E (epinephrine) hormones or neurotransmitters?

A

both

  • hormones: both are released from adrenal medulla (more E than NE) into bloodstream and can act on receptors in the body
  • neurotransmitters: both are released from neurons in CNS – NE is absolutely released as a neurotransmitter, and any neuron in CNS that releases NE also releases a small fraction of E

+ BIOL 371 (22 decks)

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