Menstrual cycle 1

Question 1

What is the key requirement for the HPG axis maintenance?

Answer 1

The pulsatile release of GnRH and gonadotrophins because when released in bolus this leads to cessation of the HPG axis cycle as it stops the release of LH and FSH

Question 2

What controls the menstrual cycle?

Answer 2

The HPG axis

Question 3

What is the length of the menstrual cycle ?

Answer 3

The length of a menstrual cycle is the number of days between the first day of menstrual bleeding of one cyctle to the onset of menses of the next cycle.

Question 4

What are the two stages of the menstrual cycle?

How long do the different stages last

Answer 4

The follicular phase (1-14) and luteal phase (14-28)

With ovulation in the middle

MC typically is 28 days (25-30)
Menstruation lasts 3-8 days

The luteal phase is fixed but the follicular phase varies

Question 5

What are the key words describing length of menstrual cycle ?

Answer 5

Less than 21 days =Polymenorrheic

More than 35 days =Oligomenorrheic

The menstrual cycle will typically be most irregular around extremes such as menopause and menarche

Question 6

Outline the changes of LH and FSH ,Progesterone and Estradiol as the cycle progresses as well as what causes these changes

Answer 6

FSH begins at a low level and at around day 14 there is an intercycle rise in FSH.As FSH has this peak, oestradiol levels decline sharply. There is also the LH surge.There is also progesterone which is found predominantly in the luteal phase as it is released from the corpus luteam

Question 7

Outline the progression of the Menstrual cycle

Answer 7

1.Begins at the late luteal /early follicular phase where progesterone begins to decline and there is a selective rise in FSH (intercycle rise of FSH).This is because if there is no pregnancy the corpus luteum will die.FSH will therefore rise because progesterone has negative feedback on hypothalamus and pituitary.As this feedback stops FSH can be released which will lead to follicle stimulation.

2.Mid follicular stage :
E2 will increase causing negative feedback which leads to a fall in FSH.This allows the selection of one follicle.

3.Mid cycle :
2 days of E2 exceeding threshold of 300pmol -positive feedback which causes an LH surge.The LH surge will lead to ovulation of dominant follicle.
The remainder of the follicle will become the corpus luteum.

4.Mid luteal phase :
There will be high progesterone as this is released form the corpus luteum.
This causes negative feedback =Low FSH/LH and this will also overcome the E2.

Question 8

What animals have menstrual cycles ?

Answer 8

Menstrual cycles only occur in humans ,primates and is named for the regular appearance of menses (shedding of the endometrial lining)

Question 9

What are Oestrus cycles ?

Answer 9

This is the cyclic appearance of behavioural sexual activity (heat /oestrus)

The animals do not menstruate but instead the endometrium will be reabsorbed if fertilisation does not take place

Day 0 of the oestrus cycle is the day of beginning of sexual receptivity

Ovulation will occur early in the cycle as high oestrogen levels stimulate sexual behaviour as well as exerting positive feedback.

Question 10

What are the different types of oestrus cycles ?

Answer 10

Poly-oestrus - go into heat several times a year

Di-oestrus-twice a year

Mono-oestrus - one breedign season usually in spring

Rabbits do not have oestrus cycles as they are induced to ovulare by mating

Question 11

What produces Inhibin ?

What are the differences

Answer 11

In the testis-Sertoli cells
In the ovary-Granulosa cells
Disulphide-linked protein dimers

Common alpha subunit with different Beta subunit giving two forms of inhibin

Both forms specifically suppress FSH secretion by pituitary without affecting LH secretion.

Question 12

What does activin do ?

Answer 12

Activin was isolated from follicular fluid which stimulates FSH secretion

Question 13

What was Follistatin found to do ?

Answer 13

This is a FSH-suppressing protein which was isolated from follicular fluid.It binds to activin with high affinity therefore neutralises the FSH-stimulating ability of activin.

Question 14

How do we know that inhibins do selectively act on FSH?

Answer 14

Ovariectomised sheep where used (removed their ovaries).
Ovaries where removed to remove any endogenous hormones.
GnRH agonist was injected in the presence and the absence of inhibin.

When injected with GnRH agonists this will act as GnRH and stimulate the release of LH.

There was no difference in the sheep with/without inhibin.

In case of sheep where FSH was observed there was no FSH in sheep treated with inhibin but the sheep without had normal FSH.

Question 15

Outline the biosynthesis of inhibins and activins

Answer 15

This occurs from 3 genes and makes a precursor protein.

A- protein-specific for Inhibin
Ba-protein -can form activin/inhibin
Bb protein-can form activin or inhibin
(These are TGFbeta superfamily of proteins )

Inhibins take 2 forms depending on Beta chain composition

(Inhibin A and Inhibin B)

Activins take 3 forms depending on Beta-chain composition

(Activin A (Beta-A homodimer),Activin Beta (Beta-beta-homodimer) and Activin AB (Ba and Bb)-heterodimer

Question 16

Where is Inhibin produced ?

Answer 16

In males -Testis(Sertoli cells )

In females -Ovary(Granulosa cells)

Question 17

How does the ratio of inhibin: activin production vary in different follicle stages?

Answer 17

In early antral stages as the follicles are growing, activins are produced in higher levels compared to inhibin.
As folliculogenesis increases , inhibins will increase in concentration.

Question 18

What evidence is there for Inhibin working against FSH ?

Answer 18

Investigated during the late follicular phase corresponding with larger antral follicles.

It was found that mice which were administered with inhibin antiserum did not have a drop in FSH.This is because the antiserum will bind to inhibin and prevent it from binding to FSH

Question 19

What is AMH?

Answer 19

Anti-Mullerian hormone which is a glycoprotein and a member of the TGFbeta superfamily.

It is expressed in males and causes regression of Mullerian ducts via apoptosis.

It has been found to also be present in the ovary

Question 20

How does AMH function in the ovaries ?How is it expressed ?

Answer 20

It is expressed by ovarian granulosa cells with levels peaking in selectable follicles (large preantral and small antral follicles) then decreasing.

AMH production in preantral follicles is variable but it has been detected from the primary stage onwards

Question 21

What is thought to be the function of AMH ?

Answer 21

It is thought to be a regulator of normal follicle growth and development.

Through:
1.Inhibiting the transition from primordial to primary follicles

2.Inhibits FSH-dependent cyclical recruitment of follicles by inhibiting FSH_stimulated aromatase and FSH receptor expression-in a normal cycle would act to prevent the over recruitment of growing follicles

Question 22

What will be the consequence if all follicles where to activate and grow at one time?

Answer 22

This would cause premature ovarian failure /menopause

Question 23

What is the window of opportunity?

Answer 23

The growth of follicles will start off FSH independent but at a certain point they become FSH dependent. As the level of FSH increases, the follicles which are at the right size at the right time will be recruited into the menstrual cycle.
They will then grow exponentially. At this stage activins will increase as it is being produced by these follicles (granulosa cells).
Oestrogen will be produced by follicles causing feedback and at this stage inhibins will be produced.This reduces the levels of FSH.The selected follicle will survive this.

Question 24

What is the FSH threshold hypothesis ?

Answer 24

This is that one follicle from a grouo of antral follicles in ovary is just atthe right stage at the right time.
This becomes the dominant follicle which survives the fall in FSH and goes on to ovulate.
This is known as selection
Can occur in either ovary,

Oestradiol levels will then rise which causes negative feedback at the pituitary causing FSH levels to fall and prevent further follicle growth.

Question 25

How does the dominant follicle survive the fall in FSH?

Answer 25

This is because it acquires LHJ receptors on granulosa cells.
As FSH falls , LH will increase.

The other follicles will end up losing their stimulant and die.

Question 26

What receptors are present on Granulosa ?

What steroids are produce in Granulosa cells

Answer 26

FSH
LH -on the dominant follicle from mid-follicular phase

Oestrogen follicluar phase driven by FSH

LH drives progesteron in luteul phase

Question 27

What types of receptors are found in theca cells?

Answer 27

LH receptors

LH will drive oestrogen and progetsterone production from theca

Question 28

When are Inhibin A vs Inhibin B more prominent in menstrual cycle?

Answer 28

Inhibin A = Increases in late follicular phase with highest levels in luteul phase as being made by corpus luteum.
It contributes to the inhibition of FSH at this phase.

Inhibin B =Highest in the early mid follicular phase. Declines in the late follicular phase.Zero in luteal phase

Question 29

What parts of the reproductive tract are affected due to hormonal changes ?

Answer 29

Endometrium
Oviduct/Fallopian tubes
Cervix
Vagina