13) Female Reproductive Endocrinology Flashcards
What occurs in terms of germ cell development to form oocytes?
- Mitosis of oogonia
- Meiosis I to form oocytes
What phase of meiosis do oocytes remain in until ovulation?
Prophase I
Oocytes are surrounded by what to form a primary follicle?
Single granulosa cell layer
How does male and female germ cell development differ?
- Males: spermatogonia are laid-down during embryogenesis, but are only activated during puberty
- Females: all oocytes are produced during in-utero development, but they are not complete until ovulation and fertilization
How are oocytes lost during in-utero development?
- May not progress through meiotic prophase
- May not successfully be enclosed in a follicle
How many oocytes are present at birth and puberty? How many ovulations occur in a lifetime?
- Birth: 1.5 million
- Puberty: 300 000
- 400 to 500 ovulations in a lifetime
What occurs in terms of the oocytes until puberty?
Waves of follicular growth and atresia
What layer do granulosa cells form? What is its function? When does it develop?
- Corona radiata
- Provides nutrition for the cell
- Develops during the 5th month of in-utero development
What occurs to granulosa cells once ovulation occurs?
They are removed
Why is a larger follicle cell mass desirable?
To allow the fingers of the oviduct to pick up the cell with ease
Where are thecal cells situated? Where are granulosa cells situated?
- Thecal cells are on the outside of the basement membrane
- Granulosa cells are on the inside of the basement membrane
What is the corpus luteum responsible for if fertilization occurs?
The production of progesterone
What occurs to the corpus luteum if fertilization fails?
Luteolysis
Which gonadotrophin do thecal cells respond to? What is the response?
- LH
- Formation of testosterone
Which gonadotrophin do granulosa cells respond to? What is the response?
- FSH
- Formation of estradiol from the testosterone produced in the thecal cells
The antrum of a follicle is high in _________.
estradiol (E2)
The estradiol produced by granulosa cells may affect which tissues?
- Brain (libido and sexual behaviour)
- Reproductive tract
What is the importance of the high estradiol within the antral follicle?
Estrogen is a powerful mitogen
_______ cells provide androgens to _______ cells.
thecal
granulosa
_______ cells produce the circulating estrogens that inhibit the secretion of GnRH, LH, and FSH.
Thecal cells
Inhibin from __________ cells inhibits FSH secretion.
granulosa
LH regulates the ________ cells, whereas __________ cells are regulated by both LH and FSH.
thecal
granulosa
When does estrogen and progesterone exert a positive feedback on the hypothalamus and anterior pituitary?
Days 12 to 14
What produces inhibin A?
Dominant follicle and corpus luteum
What produces inhibin B?
Small follicles
When is inhibin A produced? When is inhibin B produced?
- Inhibin A: luteal phase
- Inhibin B: follicular phase
What is the inhibin receptor?
- There is no specific receptor for inhibin
- Inhibin acts by inhibiting activin
What are the three phases to the follicular wave? How does the quantity of estradiol produced differ between the stages?
1) Recruitment (low E2)
2) Selection (medium E2)
3) Dominance (high E2)
What is recruitment?
- Small antral follicles are recruited
- Entry into gonadotrophin sensitive pool
What is selection?
- Follicles are selected from previously small follicles
- Ovulatory follicles emerge
- They either undergo atresia or develop further
What is dominance?
Selected follicles will ovulate
What are the levels of FSH, LH, inhibin, and estradiol during recruitment?
- High FSH
- Low LH
- No inhibin
- Low estradiol
What are the levels of FSH, LH, inhibin, and estradiol during selection?
- Low FSH
- Moderate LH
- Low inhibin
- Medium estradiol
What are the levels of FSH, LH, inhibin, and estradiol during dominance?
- Low FSH
- High LH
- High inhibin
- High estradiol
How many follicular waves occur during the follicular phase of the reproductive cycle? What do minor waves produce?
- More than one follicular wave typically occurs
- Minor waves do not result in ovulation
At which phase is FSH at its lowest point? Why?
- Selection
- The production of inhibin and estradiol inhibit FSH secretion
Estradiol exerts a positve feedback on the ______ center.
surge
The _____ center is ONLY associated with ovulation, while the ______ center is associated with other reproductive functions.
surge
tonic
What occurs to the surge center after estrogen reaches a threshold level?
Releases high amplitude, high frequency pulses of GnRH in a relatively short period of time
Why does ovulation require the rupture of healthy tissue at the surface of the ovary?
Because there are tissue layers in between the location of the oocyte and the outside of the ovary
Which tissue layer contains the oocyte prior to ovulation?
Theca externa
What are the cellular components of the oocyte at time of ovulation?
- 60-70 times larger than a typical cell
- 100 000 mitochondria
- 100 million ribosomes
- 50 times the ATP
How does the pre-ovulatory surge affect PGF2a?
Increase
What are the effects of an increase in PGF2a following the pre-ovulatory LH surge?
- Increased contraction of ovarian smooth muscle (increases follicular pressure)
- Release of lysosomal enzymes (follicle wall weakens)
How does the pre-ovulatory LH surge affect hormone secretion by the dominant follicle? What is the effect?
- Shift from estradiol to progesterone
- Increase in collagenase, which allows for the weakening of the follicle wall
What is the effect of an increase in PGE2 due to the pre-ovulatory LH surge?
- Increased blood flow to the ovary and dominant follicle
- Edema, which increases follicular pressure
When does meiosis I occur in the oocyte? When does meiosis II occur?
- Meiosis I: ovulation
- Meiosis II: fertilization
What three factors allow for the onset of ovulation?
- Elevated blood flow
- Breakdown of connective tissue
- Ovarian contractions
What do theca interna and granulosa cells become after ovulation?
Form the corpus luteum
How is the tonic center related to the corpus luteum?
- The tonic center produces low levels of GnRH to maintain basal levels of LH
- Stimulates the corpus luteum to secrete mainly progesterone
What is the effect of progesterone produced by the corpus luteum on the hypothalamus?
- Negative feedback on the GnRH neurons of the hypothalamus
- GnRH, LH, and FSH are suppressed and little estrogen is produced
What is the effect of progesterone produced by the corpus luteum on the tonic center? How does that affect the frequency and amplitude of GnRH?
- Reduces the frequency of the pulse
- Amplitude is still relatively high
- Allows follicles to grow, but not mature
What is the effect of progesterone produced by the corpus luteum on the mammary gland?
Positive feedback that promotes alveolar development
What is the effect of progesterone produced by the corpus luteum on the uterine tissue?
- Positive influence on the endometrium
- Inhibits the contraction of the myometrium
- “Progesterone block of pregnancy”
Describe the mechanism by which the luteolytic pathway is activated.
Oxytocin produced by the ovary binds to receptor and activates the synthesis of PGF2a
What are the functions of PGF2a in luteolysis? (3)
1) Increases intracellular calcium, which has apoptotic effects
2) Activates PKC, which inhibits progesterone synthesis
3) Sustained vasoconstriction, causing the endometrial lining to slough off
Describe the phases of the uterine cycle, and the days they correspond to.
1) Menstruation (1-3)
2) Proliferative phase (3-14)
3) Secretory phase (14 to 28)
How do progesterone and estradiol concentrations vary during luteolysis?
Decrease dramatically
When may hCG be detected?
6 to 12 days after fertilization
hCG has the same alpha chain as which hormones?
- FSH
- LH
- TSH
What is the function of hCG?
Stimulates the corpus luteum to maintain steroids until feto-placental unit takes over