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Neuropharmacology > Nandralone - steroid hormones > Flashcards

Nandralone - steroid hormones Flashcards

1
Q

what are steroid hormones derived from

A

cholesterol

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2
Q

where are steroid hormones typically made

A

in the periphery
endocrine glands
e.g. adrenal cortex and gonads

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3
Q

when are steroid hormones biologically active

A

when they are circulating in their ‘free’ state

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4
Q

what allows steroid hormones to pass through the BBB

A

they are lipid/fat soluble

pass through via transmembrane diffusion

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5
Q

how are steroid hormones carried in the blood

A

bound to proteins (globulins) or albumin (plasma protein)

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6
Q

testosterone conversion in the brain

A

converted to oestradiol by aromatase enzyme and then to oestrogen

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7
Q

neuroactive steroid

A

steroid that can act within the brain

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8
Q

neurosteroid synthesis

A

steroid made within the brain

directly synthesised from cholesterol in the brain

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9
Q

examples of neurosteroids

A

Pheromones
progesterone
Allopgrenanolone
Dehydroepiandrosterone (DHEA)

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10
Q

examples of neuroactive steroids

A 
Oestradiol
Progesterone
Testosterone
Glucocorticoid
Dehydroepiandrosterone (DHEA)
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11
Q

Hypothalamic–pituitary–gonadal (HPG) axis importance

A

how the brain controls production of steroids within in the gonads

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12
Q

features of how neuroactive steroids modulate activity of cells

A

regulatory function
slow - over hours, number of days
genomic action, passes through lipid membrane, enters nucleus and alters gene transcriptions to elicit downstream effects

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13
Q

non genomic action of steroids

A

can be neurosteroids or neuroactive steroids
fast
seconds to minutes
neuromodulatory function
activation of a second messenger molecule

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14
Q

steroid receptors of the nuclear receptor family are all…

A

transcription factors

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15
Q

how many different domains on a nuclear steroid hormone receptor

A

5

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16
Q

which domain is the most variable

A

the N-terminal

AF1 co-activator region

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17
Q

importance of the variable N-terminal domain

A

binds transcription factors
determines receptor activity
different in length between different receptors

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18
Q

why is the core DNA binding domain important

A

regulates receptor dimerisation

controls which genes will be activated

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19
Q

where does the core DNA binding domain bind to in DNA

A

hormone response elements (HRE)

20
Q

which domain of the steroid hormone receptor is highly conserved

A

core DNA binding domain

21
Q

importance of the hinge region domain

A

Flexible

Regulates dimerization

DNA binding

controls the movement of the receptor to the nucleus.

22
Q

role of AF2 co-activator region domain

A

ligand binding domain
where hormones bind
induce nuclear localisation signal (NLS)

23
Q

role of c-terminal domain

A

extension that connects the molecule to its pair in the homodimer or heterodimer.
may affect the magnitude of the response.

24
Q

hsp binding

A

receptor may bind to chaperone proteins

25
Q

AF1 stands for

A

activator function 1

26
Q

LBD stands for

A

ligand-binding domain

27
Q

DBD stands for

A

DNA binding domain

28
Q

ER subtypes

A

estrogen receptor subtypes alpha and beta

29
Q

PR subtypes

A

progesterone receptor subtypes A and B

30
Q

what are MR and GR

A

mineralocorticoid receptor

glucocorticoid receptor

31
Q

what enables a single steroid hormone to have many different behavioural effects within the brain

A

interconversion by metabolites eg. aromatase

32
Q

2 types of steroid hormone receptors

A

membrane steroid hormone receptors

nuclear steroid hormone receptors

33
Q

non-genomic action of steroids to control cell activity

A

neuromodulatory - FAST
bind to membrane steroid hormone receptor
activate 2nd messenger signalling cascade

34
Q

genomic action of steroids

A 
regulatory - SLOW
bind to nuclear steroid hormone receptor
translocates to nucleus
activate transcription factors 
transcribed genes mediate downstream effects

more often neuroactive steroids e.g. oestrogen/testosterone

35
Q

highly specific region of nuclear steroid hormone receptor

A

ligand binding domain

36
Q

GRE

A

glucocorticoid response element

genes that can be influenced by the presence of glucocorticoid steroid hormone

37
Q

positive glucocorticoid RE

A

when GR dimers bind and results in activation of transcription

38
Q

-ve GRE

A

involved in repression

when glucocorticoid receptors bind to transcription factors and stop genes being transcribed

39
Q

steric hindrance of GRE

A

when GR is bound to DNA
doesnt stop transcription directly
stops transcription factor binding close by
indirectly prevents transcription machinery transcribing a gene close to a GRE

40
Q

tethering GRE

A

when GR bind T factors but dont bind the DNA

41
Q

how can steroid hormones act via non-genomic mechanisms to alter ATPase activity

A

bind to phospholipids in membrane bilayer

impact membrane flexibility

42
Q

effect of allopregnanolone on GABA A receptors

A

positive allosteric modulator

43
Q

why is chronic stress dangerous

A

glucocorticoid receptors all over the body

GRE present in 20% of all genes in the genome

44
Q

CRH neurons

A

corticotropin releasing hormone

45
Q

where are CRH found

A

paraventricular nucleus of the hypothalamus

project to pituitary gland

46
Q

effect of chronic early life stress on GR expression

A

reduces GR expression (down-regulation) in the CNS

reduced negative feedback inhibition of the HPA axis

alters ability to cope with stress in later life

47
Q

which is faster genomic or non-genomic

A

non-genomic

Neuropharmacology (14 decks)

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