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Year 3- Repro > Menstrual Cycle I > Flashcards

Menstrual Cycle I Flashcards

1
Q

What is the key requirement to maintain this axis?

A

A pulsatile release of GnRH and the gonadotrophins- the cycle ceases without this

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2
Q

Briefly outline the HPO axis

A

Most of the cycle is a negative feedback cycle: Hypothalamus release GnRH–> Anterior Pituitary releases FSH+LH–> Ovary produces oestrogen and progesterone…

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3
Q

How long are most menstrual cycles?

A

28 days, most cycles are between 25-30 days

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4
Q

How long does menstruation last?

A
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5
Q

Define Polymernorrheic

A

MC<21 days

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6
Q

Define Oligomenorrheic

A

MC> 35days

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7
Q

Why is the luteal phase fixed?

A

It is 14 days dependant on the life cycle of the corpus luteum It is the follicular phase that varies

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8
Q

When is the menstrual cycle most irregular?

A
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9
Q

What are the different phases of the cycle?

A
  • Late Luteal
  • Early Follicular
  • Mid Follicular
  • Late Follicular
  • EL
    ML
    LL
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10
Q

What is the rise in FSH called?

A
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11
Q

Progesterone is predominately in the luteal phase, it comes from the….

A

Corpus Luteum

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12
Q

Which steroids are made where?

A
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13
Q

Describe the late luteal phase/early follicular phase

A

Progesterone is declining due to the death of the CL (if tehre is no fertilisation). This results in a selective increase in FSH = Inter-cycle rise in FSH
As progesterone is normally negatively feedbacking to the hypothalamus and the pituitary which would inhibit FSH
Rise in FSH will stimulate the follicle.

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14
Q

Describe the Mid Follicular phase

A
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15
Q

Describe the mid cycle

A
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16
Q

Describe the mid luteal phase

A
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17
Q

The menstrual cycle only occurs in…

A

humans, primates (Apes and monkeys), named fo the regular appearance of menses (shedding of the endometrial lining)

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18
Q

Oestrus cycle in animals is named because of…

A

The cyclic appearance of behavioural sexual activity (heat or oestrus). They do not menstruate- the endometrium is reabsorbed if fertilization does not occur.

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19
Q

Day 0 of the oestrous cycle is the day of..

A

beginning of the sexual activity

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20
Q

Why does ovulation occur ealy in the cycle?

A

High oestrogen levels stimulate sexual behaviour as well as exerting positive feedback

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21
Q

Different species have different lengths of the cycle, some are poly-oestrous which means they

A

continuous breeders- go into heat several times/year (cats, cows, pigs)

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22
Q

Di-oestrous

A

Twice/year, some only have one breeding

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23
Q

Mono-oestrous

A

One breeding season- usually spring due to better food availability, longer days etc

24
Q

-

A

Rabbits have no oestrous cycles and are induced to ovulate by mating and can conceive at any arbitrary moment.

25
Q

Describe the overall HPO axis

A

There is pulsatile release of GnRH
Negative feedback by estrogen and progesterone
BUT it is not just estrogen and progesterone, there are also activins and inhibins

26
Q

Inhibin

A

Produced by testis (Sertoli cells) and ovary (Granulosa cells)
- Disulphide-linked protein dimers
- There is a common α-subunit with different β-subunits giving two forms of Inhibin
- Both forms specifically suppress/inhibit FSH secretion by acting at the level of the pituitary without affecting - - LH secretion. Only affects FSH

27
Q

Activin

A

stimulate FSH secretion
Is released into follicular fluid
Made by granulosa cells
Stimulates/Activates FSH

28
Q

Follistatin

A

Inhibits FSH indirectly:
Binds activin with high affinity » so it prevents activin from feeding back and acting on the pituitary to inhibit FSH.
So neutralises activins ability to stimulate FSH

29
Q

How was Inhibin discovered?

A

Experiment:
Using ovariectomized (ovaries removed) (ovx) sheep, to remove endogenous hormones
GnRH agonist was injected in the presence and absence of inhibin

30
Q

Why were ovaries removed when finding inhibin effect?

A

Want to remove the instrinsic substance (ovaries), to monitor effect

31
Q

Inhibin Experiment

A

GnRH agonist will act like GnRH and will stimulate production of LH.

GnRHa stimulates LH release as expected. When add in/treat ovx ewes with Inhibin – no effect on LH.

measuring FSH. Again GnRH agonist elicits big effect on FSH release. But this time, when treat with Inhibin, see that release of FSH upon injection of GnRHa is completely suppressed/lost.

So when GnRH agonist is given with inhibin, there is no effect on LH, but almost complete suppression with FSH.

32
Q

Biosynthesis of inhibins and activins

A

occurs from 3 genes, make precursor protein:
α- protein, specific for Inhibin
βA- protein, can form either Activin/Inhibin (beta A)
βB- protein, can form either Activin/Inhibin (beta B)
These alpha and beta subunits are all members of TGF-beta superfamily of proteins.

33
Q

Forms of inhibin

A

Inhibins take 2 forms depending on β-chain composition
Inhibin A and Inhibin B

34
Q

Forms of activins

A

Activins take 3 forms depending on β-chain composition
Activin A (βA-homodimer), Activin B (βB-homodimer) & Activin AB (βAβB-heterodimer)
Activins have no alpha subunit, just combinations of the beta subunit
Same = homodimer
Different = Heterodimer

35
Q

Similiarities and Differences between activin and inhibin

A

Activin = Activates FSH
Inhibin – Inhibits FSH

Both are produced from GRANULOSA CELLS

36
Q

Ratio of activin with inhibin:

A

In the earlier antral stages, as the follicles are growing, - Activins are produced in high levels compared to inhibin.
- Activins correlate with the FSH rise in the early follicular phase

As folliculargenesis progresses, Inhibin increases in concentration compared to Activin
- Inhibin correlates with the FSH fall in the Late follicular phase

So the ratio varies.

37
Q

Further proof if inhibin effect:

A

In the experiment they took female rats and injected them with either normal rabbit serum or with an anti-serum against inhibin.

This was done in the late follicular phase where you have the big antral follicles.
In the late follicular phase you would expect to see a drop in FSH
BUT in the rats treated with the inhibin anti-serum, instead of a drop, you get a rise in FSH. This is because the anti-serum will bind inhibin and prevent it from working and therefor inhibiting FSH.

38
Q

What is an anti-serum?

A
39
Q

What is AMH?

A

glycoprotein and also a member of the TGFβ superfamily

40
Q

when is AMH expressed in males?

A

In males AMH is expressed from week 8 of development
It causes regression of the Müllerian ducts by a wave of apoptosis.

41
Q

Where is AMH expressed in females?

A

It is expressed by ovarian granulosa cells of the follicles
Levels of AMH in selectable follicles (large preantral and small antral follicles) » then decreasing
So the granulosa cells will produce AMH and it reaches its peak, then it will decease.

42
Q

What does AMH do in the follicle?

A

1) Inhibits transition from primordial to primary follicles
Women are born will all of their resting primordial follicles. Cohorts then activate and grow slowly to become a primary follicle. AMH is thought to inhibit this transition.
This was discovered from knockout mice (so AMH was not expressed in the ovary in the follciles). They found that when you remove AMH from the ovary, all the resting primordial follicles activate (this will result in early menopause or premature ovarian failure). Therefore it is important to keep the balance and have the primordial follicles develop slowly to have a longer reproductive lifespan.

2) AMH inhibits FSH-dependent cyclical recruitment of antral follicles by inhibiting FSH-stimulated aromatase and FSH receptor expression → in the normal cycle would act to prevent over-recruitment of growing follicles
Therefore a balance is needed so you don’t get over recruitment and growth of follicles.

43
Q

Over recruitment of follicles…

A

Depletes number of follicles, go to early menopause

44
Q

Once the primordial follicles start growing and progress along, the growth is FSH independent, it does not need gonadotrophins so..

A

So the follicles grow without gonadotrophins very slowly, but they reach a point in their development where they need FSH to progress.

45
Q
A

FSH levels will start to rise (as there is removal of the negative feedback from progesterone).
The follicles that are at the right stage at the right time will respond to the rise on FSH levels and will be recruited into the menstrual cycle and will grow.

46
Q
A

There is also production of activins from the granulosa cells that aid this (as it also stimulates FSH)

47
Q
A

The follicles follicle will also be production estrogen that will feedback and cause FSH to fall. BUT remember they are also producing inhibins too.

So as E2 and inhibins increase -> FSH levels fall
You will still have the dominant follicle (that has been selected despite FSH falling), but any other wave of follicles that may be at the right stage and size cannot grow further due to the drop in FSH.

48
Q

Which type of receptors are present in the granulosa?

A

FSH receptors
LH receptors – ONLY acquired When dominant follicle is selected, from the mid follicular phase onwards.

49
Q

What steroids are produced as a consequence in the graulosa?

A

Estrogen (FSH drives oestrogen production in the follicular phase)
Progesterone – ONLY when the dominant follicle has the LH receptor (LH drives progesterone in the luteal phase

50
Q

Which type of receptors are present in the Theca?

A

LH

51
Q

What steroids are produced in the Theca?

A

Androgens and progesterone driven by LH

52
Q

Where the frequency of the GnRH is high, it will favour….

A

LH production

53
Q

Where the frequency of GnRH is low, it will favour..

A

FSH production (activins are high)

54
Q

Amplitude of GnRH also varies which means

A

at some stages it is favouring synthesis than release. So in the luteal phase you get gonadotrophins accumulating in the vesicles, ready for release at the later stage

55
Q

Inhibin A

A

Is higher in the luteal phase
Is declines in the follicular phase

56
Q

The decrease in inhibin A, along with the decrease in progesterone will allow for

A

the inter-cycle rise in FSH.

57
Q

Inhibin B/A

A

Inhibin B: highest in early-mid FP (ratio of activin: inhibin) and declines in LFP (small peak at LH surge), zero in luteal phase.

Inhibin A: increases in late FP with highest levels in luteal phase (being made by CL) – contributes to inhibition of FSH in this phase. The dramatic decline in Inhibin A at the end of the luteal phase allows for increase in FSH.

Year 3- Repro (34 decks)

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