Menstrual Cycle - Levitas Flashcards
What hormones influence the menstrual cycle and where are they released from?
• GnRH (hypothalamus) – Gonadotrophin Releasing
Hormone
• FSH (anterior pituitary) – Follicle Stimulating
Hormone
• LH (anterior pituitary) – Luteinizing Hormone
• Estrogen (ovary)
• Progesterone (ovary)
What are the enzymes in hormone production and where are they produced?
3-beta-HSD:
Takes carbones off of cholesterol to make 21 carbons (mieralocorticoid or prognenolone)
17-alpha-hydroxylase:
Cuts 2 carbons off of mineralocorticoid (progesterone) to make androgens
Present in the ovaries
21-alpha-hydroxylase:
Not present in ovaries, essential for making glucocorticoids or mineralocorticoids, only in the adrenals
Aromatase:
In ovaries
Converts androstenedione and testosterone to estrogens - rate limiting stem
What is the effect of 21 alpha-hydroxylase deficiency?
Causes adrenal hyperplasia
Late onset is in young adults –> Hirsutism
At birth –> Salt losers
Too much androgen production and no glucocorticoid and mineralocorticoid production
What are the fates of a primordial follicle?
(Describe follicular stages)
- Primordial
- up to 6 million oocytes arrested in meiotic I prophase, but decline to 2 million at birth and 300,000 at puberty, 400 ovulate during a woman’s life
- recruitment
- recruitment independent of hormonal regulation about 85-14 days before ovulation
- In last 14 days receptors to FSH allow rescue from atresia
- Most follicles stay in primordial stage (reason unknown) - Preantral
- zona pellucida surrounds cell, theca layer organizes from stroma and estrogen increases
- Moves to preantral and then doomed to ovulation or apoptosis
- Those that enter the preantral stage apoptose induced by androgens
- In pregnancy and birth control pills, more cells move from primordial to preantral but then apoptose
- Preantral follicle is surrounded by a basement membrane and a thecal layer outside that. The antrum is the fluid space in the middle that grows a lot - Antral
- If rescued, can move from preantral to antral to preovulatory
- Follicular fluid produced in ntercellular space of granulosa
- Granulosa cells surround –> cumulus oophorous - Preovulatory
-has very large antrum
-zona pellucida, cumulus oophorus and many layers of granulosa cells surround the egg
• Granulosa cells enlarged and acquire lipid inclusions
• Theca becomes richly vascular , giving a hyperemic appearance
-No more 2 cell system: both theca and granulosa cells have LH receptors
What are the phases of the normal menstrual cycle and what hormones affect their transition?
- Follicular phase
Ensures that the proper number of follicles are ready for ovulation
GnRH induces FSH secretion by pituitary gland
FSH induces the ovaries/follicles to release estradiol
Negative feedback: Estradiol decreases FSH and LH secretion by the pituitary gland on the thalamus
Positive feedback: Estradiol induces LH and FSH surge from pituitary gland
Average 10-14d (but is cycle length - 14 days) - Ovulation
LH stimulates follicle explosion, opens and releases the egg - Luteal phase
Fallopian tube receives the egg
Follicle is converted into the corpus luteum which produces progesterone and estradiol
LH increases progesterone and estradiol secretion by the corpus luteum - Menstruation/Pregnancy
If no fertilized egg: decreased progesterone and estradiol secretion. In pregnancy, beta-HCG keeps the corpus luteum alive and progesterone and estradiol levels up. Otherwise lasts 14 days and then menstruation.
What is the two-cell, two-gonadotropin system
• FSH receptors present exclusively on granulosa cells
• LH receptors present only on theca cells
• The theca will produce androgens,that can be
converted to estrogens in the granulosa cells
Present in the early follicular phases (pre-antral and antral)
No longer present in preovulatoryh follicle
How is the dominant follicle selected?
• Local action : estrogen-rich environment at the level of
selected follicle will prevent atresia
• Distant action : estrogens negative feedback
relationship with FSH at the hypothamic-pituitary level
will serve to withdraw FSH support from the less
developed follicles and lead them to atresia
Inhibin B combines with estrogen for a sustained suppression of FSH secretion
At high levels estrogen exerts a positive stimulatory effect on LH release (in final follicular phase)
• Atresia = apoptosis
Graph of how hormones fluctuate in the menstrual cycle
How do insulin-like growth factors (IGFs/somatomedins) affect the menstrual cycle
• Polypeptides acting locally and function in paracrine and autocrine modes
• Structurally and functionally similar to insulin, mediate growth hormone action
• IGF-I derived from growth hormone dependent synthesis in the liver (not so important to the ovary)
• IGF-II is produced in theca , granulosa and luteinized granulosa cells
• In preovulatory follicles IGF-II stimulates
granulosa cell proliferation and aromatase activity
• Following ovulation IGF-II stimulates progesterone synthesis
• IGF-II is the most abundant IGF in human ovary and acts upon IGF-I and IGF-II receptors
Promotes LH and FSH activity
This is where PCOS mechanism originates
What happens to the oocyte 24-36 hours prior to ovulation?
• Approximately 24-36 h prior to ovulation the peak estradiol level is achieved and onset of LH surge occurs leading to :
- Maturation of oocyte in the dominant follicle : completed meiosis with reduction division
- Seals the fate of the non dominant follicles towards atresia of their oocytes
- Luteinization of granulosa in the dominant follicle , resulting in production of progesterone (luteal phase)
- Progesterone facilitate the LH action and is responsible for the midcycle FSH surge ensuring completion of LH receptors in the granulosa layer
- 15% increase in androstenedione and a 20% increase in testosterone production serve locally to increase atresia in non dominant follicles and systemically to stimulate libido
How is the oocyte expelled in ovulation?
• LH-induced cyclic AMP activity overcomes local inhibitory action of OMI (oocyte maturation inhibitor) and LI (luteinization inhibitor)
• Rise in progesterone act to terminate the LH surge as a negative feedback and influence positively midcycle rise in FSH which induce conversion of plasminogen to the proteolytic enzyme, plasmin.
E2 surge to LH surge is 14-24h, LH surge to ovulation is about 10-12h
Like an inflammatory process but aseptic, to fight the membrane
- Activity of proteolytic enzymes result in digestion of collagen in the follicular wall increasing distensibility and free the oocyte from follicular attachments
- Movement of the follicle destined to ovulate to the surface of the ovary
- Leukocytes enter the follicle prior to ovulation
- Prostaglandins E and F increase markedly in the follicular fluid with peak concentration at ovulation (contract smooth muscle cells identified in the ovary)
- Ovulation is the result of proteolytic digestion of the follicular apex , a site called the stigma
Graph of hormones and pictures of proliferation in the cycle
Ovulation is a wound leaving the ovary (blood instead of antral fluid)
This is why some women can feel ovulation (Middleschmertz)
