1 - First Half of Menstruation

Question 1

What are the two layers of the endometrium?

Answer 1

Zona functionalis

Zona basalis

Question 2

What are the 4 components of the zona functionalis?

Answer 2

Glands
Stromal cells
Glandular epithelium
Luminal epithlium

Question 3

What type of epithelium is the luminal epithelium?

Answer 3

Simple columnar

Question 4

What hormone mediates all the proliferation within the proliferative phase?

Answer 4

Estrogen

Question 5

What effect does estrogen also have on mucus?

Answer 5

Increases production

Question 6

What property of cervical mucus is maintained by estrogen?

Answer 6

Stretchy, thin mucus (enables sperm entrance)

Question 7

What effect does estrogen have on progesterone receptors?

Answer 7

Increase progesterone receptor expression

Question 8

What two classical estrogen receptors exist?

Answer 8

ERalpha

ERbeta

Question 9

Where are classical estrogen receptors found within a cell?

Answer 9

Cytoplasmic

Question 10

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

Answer 10

Membrane-bound

Question 11

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

Answer 11

Membrane bound classical ER

GPER1

Question 12

What pathways were activated when estrogen binds to these receptors?

Answer 12

Membrane:

• PI3-kinase pathway
• MAP-Kinase pathway

GPER1 (GalphaQ)

• Phospholipase C
• MAP-Kinase pathway

Question 13

What effect does progesterone have on the classical estrogen receptor?

Answer 13

Inhibition

Question 14

Which classical estrogen receptor is more important?

Answer 14

ERalpha

Question 15

BrdU is a marker of what cell activity?

Answer 15

Proliferation

Question 16

In what two components is the classical ER receptor found?

Answer 16

Uterine epithelium

Stromal cells

Question 17

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

Answer 17

Epithelium are NEITHER sufficient NOR necessary for estrogen-dependent mitogenesis

Stromal ER are necessary.

Question 18

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

Answer 18

Pacacrine

Question 19

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

Answer 19

IGF (most important)
EGF
FGF
TGF

Question 20

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

Answer 20

1) IGF-1 k/o

2) IGF-1 inhibition

Question 21

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

Answer 21

Uterus 10% size of WT

Treatment with estrogen resulted in no response

Question 22

Inhibition of IGF-1 resulted in what observation?

Answer 22

Inhibition of estrogen-induced proliferation

Question 23

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

Answer 23

Epithelial cells

Question 24

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

Answer 24

Inhibits estrogen-stimulated epithelial proliferation

Question 25

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

Answer 25

Stimulates proliferation ERalpha

Question 26

How does estrogen stimulate epithelial proliferation through stromal cells?

Answer 26

Production of IGF-1 Paracrine signalling Signals epithelium to proliferate

Question 27

What changes occur to the developing uterus if ERalpha is knocked out? (MOER mice - membrane only Estrogen receptor)

Answer 27

Infertile Atrophic uterus Other issues: cysts + NO corpus luteum

Question 28

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

Answer 28

Prevents apoptosis

Question 29

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

Answer 29

Protein secretory production E.g. lactoferrin

Question 30

Where is GPER1 found in greater quantity?

Answer 30

Epithelium

Question 31

What relation does G1 have on GPER1?

Answer 31

G1 is a specific GPER1 agonist

Question 32

What does activation of the GPER1 prevent?

Answer 32

Prevents phosphorylation of ER-alpha in stroma

Question 33

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

Answer 33

Inhibits over-activation of estrogen-induced proliferation of endometrium. Acts as a regulator.

Question 34

What three factors are important in dominant follicular selection?

Answer 34

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

Question 35

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

Answer 35

Activin / Inhibin Estradial (from follicle)

Question 36

Which cells produce activin and inhibin?

Answer 36

Granulosa cells

Question 37

What part of the menstrual cycle does activin predominate?

Answer 37

Early follicular phase | pre-antral

Question 38

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

Answer 38

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

Question 39

How does activin increase sensitivity to FSH?

Answer 39

Upregulates FSH receptor

Question 40

Where is inhibin produced?

Answer 40

Granulosa cells

Question 41

What are the 3 main functions of inhibin?

Answer 41

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

Question 42

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?

Answer 42

Granulosa cells usually convert androgen into estradiol. Estradiol has autocrine effect on granulosa cells, increasing aromatase activity. Results in more estradiol being made.

Question 43

Towards the later stages of follicular development, which cells begin expressed LH receptors? What do they begin producing?

Answer 43

Granulosa cells IGF-1

Question 44

What 3 functions does IGF-1 have?

Answer 44

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

Question 45

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

Answer 45

1) Ovulation | 2) No estradiol production

Question 46

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

Answer 46

IGF-binding protein

Question 47

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

Answer 47

FSH FSH enhances action of IGFBP-proteolytic enzymes

Question 48

Which 3 enzymes can cause proteolysis of IGF-BP?

Answer 48

Kallikreins MMPs PAPP-A

Question 49

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

Answer 49

Kisspeptin neurones within the AVPN. Estrogen acts on ERalpha

Question 50

What pulses result in the LH surge?

Answer 50

Fast pulses

Question 51

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

Answer 51

LH surge is blocked - no ovulation.

Question 52

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

Answer 52

LH surge

Question 53

What feature of oocyte meiosis is special?

Answer 53

Asymmetrical

Question 54

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

Answer 54

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

Question 55

Meiosis II is only completed in light of what process?

Answer 55

Fertilisation

Question 56

What reason is asymmetrical meiosis so important?

Answer 56

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

Question 57

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

Answer 57

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

Question 58

What pathology in oocyte meiosis is associated with ageing?

Answer 58

Loss of polarity within the oocyte.

Question 59

Microvilli are important for the binding of what important cell?

Answer 59

Spermatazoa

Question 60

What are the 2 products of Meiosis 1?

Answer 60

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

Question 61

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

Answer 61

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

Question 62

Through what two inflammatory mediators does LH stimulate ovulation?

Answer 62

Prostaglandins Plasminogen activator