Menstrual Cycle I Flashcards
What controls the menstrual cycle?
The HPG axis and pulsatile release of GnRH
- Pulsatile release of GnRH and gonadotrophins is fundamental for maintaining the HPG axis and fertility
- No pulsatile release = cessation of menstrual cycle
What is the normal length of a menstrual cycle?
- The length of a menstrual cycle is the number of days between the first day of menstrual bleeding of one cycle to the onset of menses of the next cycle
- Median duration of MC is 28 days with most cycles between 25=30 days
- Menstruation lasts 3-8 days, written as 7/28 or 5-6/27-32
What is it called if the menstrual cycle is less than 21 days?
polymenorrheic
What is it called if the menstrual cycle is more than 35 days?
oligomenorrheic
What phases is the menstrual cycle made up of?
Follicular phase and luteal phase
Luteal phase»_space; ovulation»_space; follicular phase
How long is the luteal phase?
Always 14 days - it’s independent from the life cycle of the corpus luteum
If there’s any variation in a MC, it’s usually in the follicular phase
What hormone is predominantly high during the luteal phase?
Progesterone
What is the rise in FSH called?
The intracycle rise in FSH
What happens to FSH when oestrogen levels rise?
FSH goes down
Why do different cells make different steroids?
Different enzymes are present in different cellular compartments
Where is aromatase found and what does it do?
Granulosa cells and it can convert androgens into oestrogens - this process is driven by FSH
What receptors are found on granulosa cells ONLY?
FSH receptors
Where are androgens made?
In the theca cells because they have the specific enzymes that convert cholesterol into androgens
What happens in the late luteal/early follicular phase in the menstrual cycle?
- Progesterone declines because of the death of corpus luteum (no pregnancy)
- Progesterone inhibits FSH (through negative feedback on the hypothalamus and the pituitary) during pregnancy
- Only FSH is raised (aka the inter-cycle rise)
What happens in the mid-follicular phase of the of the MC?
- FSH stimulates follicles, they grow and become antral follicles
- Antral follicles produce oestrogen
- Rise in oestrogen means FSH falls due to negative feedback, this allows the selection of the dominant follicle
What happens during the mid of the cycle?
- Dominant follicles produces a lot of oestrogen
- Oestrogen has to be sustained and exceed the threshold of 300pmol
- Feedback switches from negative to positive, causes LH surge
- LH surge causes ovulation of the dominant follicle
What happens during the mid-luteal phase?
- After ovulation the follicle becomes a corpus luteum
- Corpus luteum makes a lot of progesterone which exerts negative feedback and keeps LH/FSH low
- There’s a peak of oestrogen coming from the CL but progesterone dominates and negative feed back is maintained
What is the different between oestrus and the menstrual cycle?
- All mammals have cyclical ovarian function & the similar reproductive system (in terms of HPG axis) to produce a mature egg(s) and the necessary sex steroids
- Menstrual cycles occur only in humans, primates (apes and monkeys) & is named for the regular appearance of menses i.e. shedding of then endometrial lining
- Oestrus cycle is when animals go into heat and it’s characterised by the animals behaviour
What is the oestrus cycle?
- The cyclic appearance of behavioural sexual activity (heat or oestrus)
- They do not menstruate – the endometrium is reabsorbed if fertilization does not occur
- Day 0 of the oestrous cycle is the day of beginning of sexual receptivity
- Ovulation usually occurs early in cycle as high oestrogen levels stimulate sexual behaviour as well as exerting positive feedback
- Different species have different lengths of cycles
What are the different types of breeding cycles in animals?
- Polyestrus
- Monoestrus
- Seasonal polyestrus
What is a polyestrus breeding cycle?
The animal can cycle during the entire year, independently of environmental cues.
What is a monoestrus breeding cycle?
- These are animals which have only one cycle per year ie the wolf, and the fox.
- Aim to give birth in the spring because there’s more food availability, longer days and less chance of predators
What is a seasonal polyestrus breeding cycle?
These animals only cycle during a determined season, in response to specific environmental cues, such as an increase or decrease of light hours.
- Short day breeders: such as the ewe, nanny and doe, start cycling as the days get shorter in the fall.
- Long day breeders: on the other hand, are animals such as the mare that start cycling as the days are getting longer in the spring
What 2 proteins can also give feedback like oestrogen and progesterone?
Inhibin and activin
What produces inhibin?
- Sertoli cells in the testis
- Granulosa cells in the ovary
What is the structure of inhibin?
- Disulphide-linked protein dimers
- Common α-subunit with different β-subunits giving two forms of Inhibin (inhibin A and B)
What do inhibin A and B do?
- Both forms specifically suppress FSH secretion by pituitary without affecting LH secretion
- Acts at the level of pituitary (not hypothalamus)
What does activin do?
- Stimulates FSH secretion
What is follistatin?
FSH-suppressing protein from follicular fluid – binds to activin with high affinity » neutralizes FSH-stimulating ability of activins
How many genes make the precursor protein for me inhibin and activin?
3 genes
How many proteins are made from the precursor protein of inhibin/activin?
3 different proteins made:
- alpha protein: specific for inhibin
- Beta A protein: can form either activin or inhibin
- Beta B protein: can form either activin or inhibin
They are all part of the TGF-beta super family of proteins
How many forms can activin take?
3 forms depending on the beta chain composition:
- Activin A (Beta-A homodimer)
- Activin B (Beta-B homodimer)
- Activin AB (Beta-A Beta-B heterodimer)
Do activins have an alpha subunit?
no
Why are these so many subtypes of inhibin and activin?
Inhibin will always inhibit FSH and activins will always stimulate/activate FSH but different sub-types are made at different stages of the menstrual cycle
Which protein (out of activin and inhibin) is made more of during the early antral phases?
- In early antral phases, more activins are made compared to inhibin. correlates with an increase in FSH during that phase
- As folliculogenesis progresses, inhibin increases in concentration, correlates with a decrease in FSH during that phase
Which protein is found during the pre-antral follicle stage?
Activin B
How is there an increase inhibin B as the follicle grows?
- Activin makes FSH
- FSH stimulates the production of the alpha subunit as the follicle grows
- There’s an increase in Inhibin B
What proteins are found when the dominant follicle is chosen?
There’s an increase in Inhibin A and a decrease in Inhibin B
What proteins are found when there is a corpus luteum?
Inhibin A and no Inhibin B
What is AMH (Anti-Mullerian hormone)?
A glycoprotein and also a member of the TGFβ superfamily
When is AMH expressed in males?
from week 8 of development - causes regression of the Müllerian ducts by a wave of apoptosis
Where is AMH expressed in ovaries?
- 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 has been detected from the primary stage onwards – different in different species
How is AMH distributed in follicles?
- Around the small early antral follicles, there’s (staining) AMH
- AMH (staining) decreases in the large pre-ovulatory follicles
- No staining in the theca at all
What is the purpose of AMH in females?
A regulator of normal follicle growth and development
How does AMH act during folliculogenesis?
- Inhibits transition from primordial to primary follicles – prevents mass activation and growth of follicles
• However, there’s no AMH receptors on the primordial follicles - 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
• At some point AMH levels falls and FSH recruits follicles
What is preantral follicle growth?
FSH independent
What does the inter-cycle rise of FSH do?
- only the follicles at the right stage at the right size will respond to the FSH and they will be recruited to the menstrual cycle to grow exponentially.
- Activin is also made by the granulosa cells in the eggs to stimulate FSH and aid this process
What causes the intercycle rise in FSH to decrease?
Granulosa cells also make oestrogen (gives negative feedback) and inhibin later on so the FSH levels fall – so only one dominant follicle survives, the rest can’t grow further and die.
How is a dominant follicle selected?
- One follicle from the group of antral follicles in ovary is just at the right stage at the right time
- This becomes the dominant follicle which survives fall in FSH and goes onto ovulate
- The DF follicle will have more FSH receptors, binds to FSH better, has a lower threshold for FSH and develops LH receptors
What happens to LH as FSH decreases?
LH increases
What receptors are found in granulosa cells and what steroids are produced as a result of these receptors?
- FSHr, only the dominant follicle granulosa cells will have LHr from the mid-follicular phase onwards
- Oestrogen and progesterone once LHr has been acquired
What receptors are found in theca cells and what steroids are produced as a result of these receptors?
- LHr only
- Progesterone and androgens
Describe Inhibin B levels throughout the cycle.
highest in early-mid follicular phase and declines in LFP (small peak at LH surge), zero in luteal phase.
Describe Inhibin A levels throughout the cycle.
- increases in late follicular phase 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.
What do the frequency and amplitude of GnRH decide?
- Frequency decides whether LH or FSH is released
- Amplitude decides whether synthesis or release is phase
What parts of the reproductive tract do oestrogen and progesterone affect?
- Endometrium
- Oviduct/Fallopian tubes
- Cervix
- Vagina - changes in vaginal epithelial cells
