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HRM > 1 - First Half of Menstruation > Flashcards

1 - First Half of Menstruation Flashcards

1
Q

What are the two layers of the endometrium?

A

Zona functionalis

Zona basalis

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2
Q

What are the 4 components of the zona functionalis?

A

Glands
Stromal cells
Glandular epithelium
Luminal epithlium

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3
Q

What type of epithelium is the luminal epithelium?

A

Simple columnar

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4
Q

What hormone mediates all the proliferation within the proliferative phase?

A

Estrogen

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5
Q

What effect does estrogen also have on mucus?

A

Increases production

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6
Q

What property of cervical mucus is maintained by estrogen?

A

Stretchy, thin mucus (enables sperm entrance)

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7
Q

What effect does estrogen have on progesterone receptors?

A

Increase progesterone receptor expression

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8
Q

What two classical estrogen receptors exist?

A

ERalpha

ERbeta

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9
Q

Where are classical estrogen receptors found within a cell?

A

Cytoplasmic

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10
Q

Given the effects of estrogen were happening too quickly in the context of nuclear-hormone activity, where were two other ER found?

A

Membrane-bound

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11
Q

What are the names of these two versions that were found?

A

Membrane bound classical ER

GPER1

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12
Q

What pathways were activated when estrogen binds to these receptors?

A

Membrane:

  • PI3-kinase pathway
  • MAP-Kinase pathway

GPER1 (GalphaQ)

  • Phospholipase C
  • MAP-Kinase pathway
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13
Q

What effect does progesterone have on the classical estrogen receptor?

A

Inhibition

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14
Q

Which classical estrogen receptor is more important?

A

ERalpha

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15
Q

BrdU is a marker of what cell activity?

A

Proliferation

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16
Q

In what two components is the classical ER receptor found?

A

Uterine epithelium

Stromal cells

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17
Q

Using recombinant animal studies, what was the conclusion regarding estrogen receptors and their location within the endometrium?

A

Epithelium are NEITHER sufficient NOR necessary for estrogen-dependent mitogenesis

Stromal ER are necessary.

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18
Q

What method of communication do stromal cells have with epithelial cells?

A

Pacacrine

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19
Q

What paracrine factors are produced by stromal cells, and which is the most important?

A

IGF (most important)
EGF
FGF
TGF

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20
Q

What 2 experiments confirmed IGF-1 to be the most important paracrine factor in stromal-induced epithelial proliferation?

A

1) IGF-1 k/o

2) IGF-1 inhibition

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21
Q

What two important findings occurs in the IGF-R K/o experiment?

A

Uterus 10% size of WT

Treatment with estrogen resulted in no response

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22
Q

Inhibition of IGF-1 resulted in what observation?

A

Inhibition of estrogen-induced proliferation

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23
Q

Where, importantly, is the IGF-1 receptor expressed in great quantity?

A

Epithelial cells

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24
Q

What change occurs with the administration of PPP, an IGF-1 receptor inhibitor?

A

Inhibits estrogen-stimulated epithelial proliferation

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25
Q

What effect does estrogen have on epithelial cells, and through what receptor?

A

Stimulates proliferation

ERalpha

26
Q

How does estrogen stimulate epithelial proliferation through stromal cells?

A

Production of IGF-1
Paracrine signalling
Signals epithelium to proliferate

27
Q

What changes occur to the developing uterus if ERalpha is knocked out?

(MOER mice - membrane only Estrogen receptor)

A

Infertile
Atrophic uterus

Other issues: cysts + NO corpus luteum

28
Q

What is the function of the classic ERalpha within the epithelial cells?

A

Prevents apoptosis

29
Q

Together, epithalial and stromal ERalpha, is necessary for what?

What protein?

A

Protein secretory production

E.g. lactoferrin

30
Q

Where is GPER1 found in greater quantity?

A

Epithelium

31
Q

What relation does G1 have on GPER1?

A

G1 is a specific GPER1 agonist

32
Q

What does activation of the GPER1 prevent?

A

Prevents phosphorylation of ER-alpha in stroma

33
Q

What resulting effect occurs by inhibiting the phosphorylation of ER-alpha in the stroma?

A

Inhibits over-activation of estrogen-induced proliferation of endometrium.

Acts as a regulator.

34
Q

What three factors are important in dominant follicular selection?

A

1) OSFs
2) Increase in sensitivity to FSH
3) Insulin-life growth factors

35
Q

How is the follicle’s sensitivity to insulin mediated? Through which substances?

A

Activin / Inhibin

Estradial (from follicle)

36
Q

Which cells produce activin and inhibin?

A

Granulosa cells

37
Q

What part of the menstrual cycle does activin predominate?

A

Early follicular phase

pre-antral

38
Q

What 4 effects does activin have in the early follicular phase?

A

1) Granulosa cell proliferation
2) Increase aromatase expression
3) Increases FSH sensitivity
4) Increases FSH production

39
Q

How does activin increase sensitivity to FSH?

A

Upregulates FSH receptor

40
Q

Where is inhibin produced?

A

Granulosa cells

41
Q

What are the 3 main functions of inhibin?

A

1) Suppress FSH production
2) Increase FSH sensitivity
3) Stimulate thecal cell LH-stimulated androgen production

42
Q

In response to increasing levels of activin / inhibin, how does the production of estradiol from granulosa cells result in a positive feedback loop for more estradiol?

A

Granulosa cells usually convert androgen into estradiol.

Estradiol has autocrine effect on granulosa cells, increasing aromatase activity.

Results in more estradiol being made.

43
Q

Towards the later stages of follicular development, which cells begin expressed LH receptors?

What do they begin producing?

A

Granulosa cells

IGF-1

44
Q

What 3 functions does IGF-1 have?

A

1) Increase follicular fluid secretion
2) Increase steroidogenesis
3) Increase granulosa cell proliferation and survival

45
Q

IGF-1 K/o studies resulted in what conclusions in regard to its necessity for?

A

1) Ovulation

2) No estradiol production

46
Q

What protein stops IGF-1 from binding and having an effect?

A

IGF-binding protein

47
Q

What hormone inhibits IGF-BP? What’s the mechanism?

A

FSH

FSH enhances action of IGFBP-proteolytic enzymes

48
Q

Which 3 enzymes can cause proteolysis of IGF-BP?

A

Kallikreins
MMPs
PAPP-A

49
Q

In the context of ovulation, where does the increasing levels of estrogen act within the brain? On what receptor?

A

Kisspeptin neurones within the AVPN.

Estrogen acts on ERalpha

50
Q

What pulses result in the LH surge?

A

Fast pulses

51
Q

Mutations in Kiss 1 / GPR54 have what effect on ovulation?

A

LH surge is blocked - no ovulation.

52
Q

What process stimulates the progression of meiotic division from prophase 1 to metaphase II?

A

LH surge

53
Q

What feature of oocyte meiosis is special?

A

Asymmetrical

54
Q

What two important features / machinery is important to facilitate asymmetrical meiosis?

A

1) Spindle positioning (microfilamines, myosins, MLC-kinases)
2) Cortical granule / microvilli organisation (small GTA-ases)

55
Q

Meiosis II is only completed in light of what process?

A

Fertilisation

56
Q

What reason is asymmetrical meiosis so important?

A

Ensures oocyte is given all intracellular machinery (organelles) and cytoplasmic store of energy.

57
Q

For what reason is spindle positioning / cortical granule / microvilli organisation so important?

A

Ensures sperm don’t penetrate through the side of important information.

58
Q

What pathology in oocyte meiosis is associated with ageing?

A

Loss of polarity within the oocyte.

59
Q

Microvilli are important for the binding of what important cell?

A

Spermatazoa

60
Q

What are the 2 products of Meiosis 1?

A

1) Large, polarised secondary oocyte (1/2 chromosomes, all cytoplasm)
2) Small polar body (1/2 chromosomes + no cytoplasm)

61
Q

So what are the 3 functions of LH around the time of day 14?

A

1) Resumption of meiosis
2) Ovulation
3) Progesterone secretion

62
Q

Through what two inflammatory mediators does LH stimulate ovulation?

A

Prostaglandins

Plasminogen activator

HRM (9 decks)

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