Endocrine signalling and reproductive biology 1 + 2 Flashcards

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1
Q

When were hormones identified?

A

1900s

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2
Q

polytene chromosomes

A

large chromosomes from drosophila

chromosome puffs - chromatin opening

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3
Q

nuclear receptor ligands

A

testosterone, oestradiol, cortisol, AT retinoid acid

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4
Q

structure of ligands

A

aromatic rings - lipophilic

dissolve and get to the nucleus

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5
Q

receptors

A

glucocorticoid, thyroid hormone, progesterone, oestrogen

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6
Q

what do nuclear receptors promote?

A

transactivation

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7
Q

what are steroid hormones based on?

A

CPPP nucleus - 17 carbons

cholesterol

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8
Q

classes of steroid hormones (carbons)

A

18 - oestradiol
19 - testosterone
21 - progestrone, cortisol and aldosterone
27 - secosteroid, broken ring

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9
Q

what groups can be added to make different hormones?

A

methyl, ketone, hydroxyl

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10
Q

what does StAR do?

A

steroiodenic acute regulatory protein - regulate cholesterol transfer within mitochondria

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11
Q

where does steroid hormone synthesis control happen?

A

mitochondria

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12
Q

acute and chronic hormone control effects

A

acute - increase calcium and cAMP

stAR and synthetic enzymes

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13
Q

catabolism of steroid hormones

A

can add hydrophilic groups to make it more water soluble

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14
Q

what does thyroid secrete?

A

T3 and T4

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15
Q

where does synthesis of throid hormone occur and what happens?

A

thyroid epithelia
protein suicide of thyroglobulin
catalysed by thyroperoxidase
make DIT and MIT

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16
Q

explain synthesis of thyroid hormone

A
thyroglobulin and iodide
iodine and tyrosine = MIT and DIT
linked to form T3 and T4
thyroglobulin colloid
lysosome cleaves and release hormone
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17
Q

how is thyroid hormone synthesis turned on or off?

A

deiodinases

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18
Q

what receptors bind chaperones in cytoplasm?

A

aldosterone, oestrogen, progesterone, gluocorticoid

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19
Q

class 3 receptors are present where? examples?

A

nucleus

thyroid hormone, retinoic acid and vitamin D

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20
Q

3 main domains of nuclear receptors

A

DNA binding domain
ligand binding domain
Unique N terminal domain

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21
Q

LBD

A

binds ligand

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22
Q

what does the LBD form?

A

ligand binding pocket that restricts what may bind

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23
Q

what may the LBD also be required for?

A

dimerisation
interaction with chaperones
interaction with co-regulators

24
Q

DBD - structure

A

8 cysteine residues
2 alpha helices perpendicular
2 zinc ions - recognition helix
C terminal extension

25
Q

CTE

A

mediates amino acid nucleotide interactions

26
Q

N terminal domain

A

variable

AF1 region

27
Q

AF1 region

A

important for ligand dependent transactivation

28
Q

hinge region

A

N terminal domain

flexible

29
Q

Hormone response element

A

positions nuclear receptors and complexes recruited by them close to gene to be transcribed

30
Q

what can sequence of HRE dictate?

A

whether receptor will activate or repress transcription of neighbouring promoter

31
Q

4 classes of nuclear receptor based on what?

A

interaction with HRE

32
Q

class 1 DNA binding sequence

A

AGAACA

33
Q

all other receptors DNA binding sequence

A

AGGTCA

34
Q

what repeat does class 1 HRE and receptors use?

A

inverted repeat separated by 3 nucleotides - IR3

35
Q

what will activate class 1 HRE?

A

AR, GR, MR, PR

36
Q

AR and class 1 HRE

A

also uses DR3 for specific control

37
Q

class 2 HRE nuclear receptors

A

IR3 of AGGTCA

38
Q

what uses class 2 HRE?

A

ER for specific control

39
Q

what do class 3 HRE nuclear receptors use?

A

direct repeat AGGTCA

1 to 5 rule - number of nucleotides spacing repeat

40
Q

Class 4 HRE nuclear receptors

A

binds as monomers

NGF1B aaaAGGTCA

41
Q

2 halves of bipartite HRE

A
1 = more like consensus site , recognised by DBD
2 = co-operative binding of second DBD to less conserved site
42
Q

3 parts of promoter

A

TATA box
initiator element
dowstream promoter element

43
Q

how is nuclear receptor activating transcription achieved?

A

RNA polymerase 2 machinery of basal promoter

44
Q

What is the PIC?

A

RNA polymerase 2, transcription factors eg TF2B

45
Q

how do nuclear receptors promote formation of stable PIC?

A

help PIC assemble by making direct contact with components of basal transcription machinery
recruit co-activators, promote PIC assembly

46
Q

what is chromatin?

A

repeating array of DNA-protein structures called nucleosome, DNA wrapping around histone octamers

47
Q

what can change properties of nucleosome?

A

covalent modification of lysine, arginine, serine residues of histone N-terminals

48
Q

what are the steroid receptor co-activators?

A

SRC1,2,3

49
Q

what do SRC1,2,3 do?

A

bind NR and have histone deacetylase activity and promote association proteins
recruit PIC

50
Q

short alpha-helical segment of SRC

A

NR box
LXXLL - lysine separated
interacts with hydrophobic groove on LBD when bound to agonist

51
Q

shutting of the system - how is it done?

A

chaperone protein eg p23 promote removal of NR and RNA pol 2 from DNA
covalent modification of co-activators
eg acetylation of SRC3

52
Q

SMRT/NCoR

A

2 nuclear receptor interaction domains with 2 amino acids
repressor activity in N terminal region
recruit histone deacetylases

53
Q

uses of anti-hormones

A

hormone dependent tumours eg breast and prostate

54
Q

bind inverse agonist

A

helix 12 shifts to N terminus of antagonist bound LBD

inhibit binding of co-activators and promote binding of co-repressor

55
Q

Negative response element

A

hormone bind

HDAC activity and repression