Lecture 6: The Menstrual Cycle Flashcards
What is the length of the menstrual cycle?
24-35 days
What is the duration of bleeding?
Less than 8 days
What is the HPO axis?
Hypothalamic-pituitary-ovarian axis
What is the proliferative phase of the menstrual cycle?
The follicular phase
From day 1 – ovulation
Signficance: this is the VARIABLE region where the length of the time can change
Which phase of the menstrual cycle is variable?
The Follicular/Proliferative phase
What are the hormones that are salient in the HPO (HPG axis)?
- GnRH (hypothalamus)
- FSH
- LH
- Estradiol (ovary)
- Progesterone (ovary)
What is the significance of the increase in frequency/amplitude of mid-cycle GnRH pulsatile secretion?
Favors the LH surge necessary for ovulation
How does the pulsatile secretion of follicular phase compare with luteal phase?
Higher frequency and lower amplitude characterizes follicular phase over luteal phase
Luteal phase is less frequent and high amplitude
What secretes GnRH?
GnRH neurons in the hypothalamus
What are the 3 key points of hypophyseal-anterior pituitary relationship in HPO axis?
Point 1: When appropriately stimulated, hypothalamic neurons secrete either releasing or inhibiting hormones to the capillary plexus
Point 2: GnRH travels through the portal veins to the anterior pituitary where they stimulate or inhibit release of hormones from ant. Pituitary
Point 3: Anterior pituitary hormones are secreted in the SECONDARY capillary plexus
What is the acronym for shit released by anterior pituitary?
FLAT PEG FSH LH ACTH TSH Prolactin Endorphins Growth hormone
What is released by posterior pituitary?
ADH
Oxytocin
What cells secrete FSH and LH in pituitary?
The Gonadotrope cells
What is the significance of the glycosylated polypeptides?
Alpha and Beta chain are located on the following hormones:
1. FSH 2. LH 3. hCG 4. TSH
What is the significance of LH and hCG?
Very similar….
Same alpha chain, different beta chain
Consequence: LH and hCG can act on same receptor
Help to regulate/mess up menstrual cycle
What is an oocyte?
Germ cells in the ovary
When do women have all their oocytes?
At birth
Has supporting cells (granulosa and theca cells) surrounding them
When do follicles begin to be recruited?
20 weeks in utero
What is are the key checkpoints in a woman’s reproductive life?
6-8 weeks: oogenesis begins 16-18 weeks: 6 million oocytes Birth = 2 million oocytes Puberty = 300,000 oocytes Menopause = 0 oocyte
How are follicles recruited?
They are recruited from the primordial stage to the primary stage
Little is known about the initiation
When are follicles gonadotropin dependent?
At the secondary follicle stage
What is the significance of FSH?
- Stimulates granulosa cell proliferation
- Stimulates aromatase activity in granulosa cells
- stimulates conversion of androgens to estrogens
- Upregulates FSH and LH receptors
How is the follicular phase regulated?
Serum estradiol concentrations peaks 1 day before ovulation
Estrogen results in NEGATIVE feedback on pituitary and hypothalamus
-decreases FSH
Once estradiol reaches a threshold, estrogen feeback becomes STIMULATORY and results in increase in GnRH pulse frequency
-this leads to LH surge
So estrogen can be both inhibitory and stimulatory
What is the LH surge?
Cause release of oocyte from follicle 36 hours after beginning of LH surge
- leads to luteinization of the granulosa cells with increased production of progesterone - causes resumption of meiosis of the oocyte and release of 1st polar body
How long does it take for egg to pass from fallopian tube to uterus?
3-4 days
When must fertilization occur?
Within 24 hours of ovulation or ovum degenerates
How are the gonadotropins inhibited during luteal phase?
Progesterone and estrogen inhibits their release
What is the function of estrogen?
- In the luteal phase, inhibits release of gonadotropins initially, then stimulates LH release for ovulation
- Promotes reconstruction and growth of the endometrium
- Glands lined by low columnar epithelium cells
- MITOSES become PROMINENT
What is the function of progesterone?
- LIMITS growth, mitosis and DNA synthesis
- Increased tortuosity of glands
- intensified coiling of spiral vessels
- Secretion of glycoproteins and peptides into cavity
What happens in the luteal phase if fertilization does NOT occur?
- corpus luteum degenerates after 14 days
- estrogen and progesterone levels fall
- withdrawal of progesterone causes secretory endometrium to slough
- As estradiol falls, FSH levels slowly rise again in ABSENCE of negative feedback
What does aromatase do?
Acts on both testosterone and androstenedione
Converts former to estradiol
Converts latter to estrone
What are cumulus cells?
The granulosa cells around the oocyte in a Graafian follicle
-at this point, oocyte has its own layer of granulosa cells while other granulosa cells surround antrum
What causes endometrium to slough?
Withdrawal of progesterone
What happens if fertilization occurs?
Embryo begins to make hCG
hCG maintains corpus luteum
progesterone and estrogen secretion continues so there is no additional menstruation
When is body temperature the highest?
AFTER ovulation
Why is body temperature not a good way to check when you should have sex?
Because it is after ovulation so less time…rather than measuring LH levels which is right before ovulation
What is the role of inhibin in women?
Produced by granulosa cells (produced by sertoli cell in men)
Blocks FSH synthesis and secretion in pituitary
-decreases pituitary GnRH receptors
Increases LH receptors in theca cells
Competes for activn receptor and INACTIVATES activing
What is Inhibin B used for in women?
Follicular Phase
Kind of counterintuitive nomenclature logic
What is Inhibin A used for in women?
Luteal phase
Kind of counterintuitive nomenclature logic
What is the significance of activin?
- Produced in gonads and pituitary to AUGMENT FSH actions
- activin enhances GnRH activity in the pituitary
- augments FSH secretion
- enhances GnRH receptor production
- Activin in the follicle
- promotes granulosa proliferation
- increases FSH receptors
- Increases FSH stimulation of aromatase and increases androgen production
Why do we have activin and inhibin on top of all the other shit?
We don’t know
Acts at level of pituitary and follicle
What is the decidualization process in menstruation?
It is a characteristic of endometrium in a pregnant uterus
- response to progesterone
- an adaptation of the uterus to enable implantation of the embryo
When does the decidualization process begin?
In the luteal phase under influence of progesterone
-mediated by autocrine and paracrine factors
What is the point of decidualization of endometrium?
- Control invasive nature of trophoblast
- important for endometrial hemostasis during menstruation and implantation
- Histologically-distinct appearance: differentiation of the spindle-shape stromal fibroblasts into plump secretory decidual cells
What are the key regulatory steps that we need to know?
- Early follicular
-no negative feedback from estrogen and progesterone
-increase in GnRH pulse frequency
-rising FSH - Mid follicular
-Rising estrogen (from follicle) SUPPRESSES gonadotropin secretion - Pre ovulation:
-CHANGE to positive feedback
-Estradiol threshold reached
-LH surge - Post ovulation:
Increase in progesterone and estrogen
Decrease in FSH and LH - End luteal phase:
-Loss of corpus luteum
-Decrease progesterone and estrogen
-Loss of negative feedback on FSH so increase FSH
What is important to know about estrogen’s role in the follicular phase?
Estrogen starts by inhibiting FSH/LH
However, right before ovulation, as the estradiol threshold is reached, it STIMULATES LH release for LH surge
