The menstrual cycle and its hormonal control Flashcards
Define menarche. Is this mainly hormonal or ovarian ?
Occurs towards the end of puberty and marks the beginning of potential fertility. (maturation of GnRH pulsatility so primarily hypothalamic)
Define menopause. Is this mainly hormonal or ovarian ?
Occurs about 45 – 55 y (average 51 yrs ) and marks the end of natural fertility.
“Exhaustion” of primordial follicles so primarily ovarian
Define Premature Ovarian Failure (POF). Are there any treatments for it ?
– Premature Ovarian Failure (POF)
Menopause can occur in women under the age of 40 (idiopathic, autoimmune disorders, genetic disorders such as Fragile X, chemotherapy, radiation)
– Symptoms can be treated with oestrogen replacement (hormone replacement therapy – HRT)
Identify the main phases/events of the menstrual cycle;
-Lasts around 28 days.
-Starts with follicular phase, lasting approximately 14 days.
This includes mences (uterine bleeding) from day 1 to approx day 5 (first day of menstrual bleeding denotes day 1 of the menstrual cycle)
-Around day 14, ovulation occurs.
-Following ovulation, luteal phase occurs, also lasting about 14 days.
Identify the main ovarian events occurring during the menstrual cycle.
In follicular phase:
- Multiple follicles develop, from day 1 to day 7
- Around day 7, one follicle becomes dominant
- From day 7 to approx day 14, dominant follicle matures
In luteal phase:
- Corpus lutem functions, from day 14 (following ovulation) to approx day 25
- Corpus lutem degenerates around days 25-28
Describe the main hormonal patterns of FSH, LH, estrogen, progesterone, and inhibin in the menstrual cycle.
- FSH: Increases in early part of follicular phase, then steadily decreases throughout remainder of cycle EXCEPT small midcycle peak.
- LH: Constant during most of follicular phase, then large midcycle increase (LH surge) peaking ~18h before ovulation. Then rapid decrease with further slow decline during the luteal phase.
- Oestrogen: Low and stable for 1st week, increases rapidly in 2nd weeks, starts to decline before LH peak. Then second increase due to corpus luteum in last few days of cycle.
- Progesterone: Low level due to ovary release during follicular phase with small increase just before ovulation. Soon after ovulation, large increase due to CL release, then similar pattern to oestrogen.
- Inhibin: Similar pattern to oestrogen ie increases in late follicular phase, remains high during luteal phase, decreases as corpus luteum degenerates.
Describe the feedback effects of ovarian hormones.
- Oestrogen, in low plasma concentrations, causes the anterior pituitary to secrete less FSH and LH in response to GnRH and also may inhibit the hypothalamic neurons that secrete GnRH.
RESULT: -ve feedback inhibition of FSH and LH secretion during the early and middle follicular phase. - Inhibin acts on the pituitary to inhibit the secretion of FSH.
RESULT: -ve feedback inhibition of FSH secretion throughout the cycle. - Oestrogen, when increasing dramatically, causes anterior pituitary cells to secrete more LH and FSH in response to GnRH. Oestrogen can also stimulate the hypothalamic neurons that secrete GnRH.
RESULT: +ve feedback stimulation of the LH surge, which triggers ovulation. - High plasma concentrations of progesterone, in the presence of oestrogen, inhibit the hypothalamic neurons that secrete GnRH.
RESULT: -ve feedback inhibition of FSH and LH secretion and prevention of LH surges during the luteal phase and pregnancy.
FSH
- When does it reach its max ?
- What is its function ?
FSH
• MAX: The concentration of FSH in the blood rises to its maximum during the follicular phase of the menstrual cycle.
• FUNCTION: In the first week of the follicular phase it stimulates the growth of medium sized follicles. Granulosa cells of the ovary express FSH receptors during the follicular phase of the menstrual cycle, so FSH stimulates Granulosa cells to androstenedione to oestrodiol 17β.
What is the homologous structure of Granulosa cells in males ?
Granulosa cells are homologous to the Sertoli cells of the testis.
What is the homologous structure of Theca cells in males ?
Theca cells are similar to Leydig cells in males.
LH
- Describe its levels in the menstrual cycle
- What is its function ?
LH
• MAX: The levels of LH vary during the follicular and secretory phases of the menstrual cycle. 12h before ovulation LH rises dramatically (stimulated by an increasing rate of secretion of oestrodiol-17β)
• FUNCTION: during the secretory phase it stimulates steroid hormone synthesis by the corpus luteum + stimulates androstenedione synthesis by Thecal cells.
Describe the main events occurring to the endometrium throughout the uterine phases.
- In menstrual phase, breakdown of endometrium thickness.
- In proliferative phase, builds up again.
- In secretory phase, no breakdown of build up, but significant amount of development in walls of tissue (secretory phase includes an ischemic phase at the very end of it, before menstrual phase)
Describe the hormonal control of estrogen synthesis. Which phase does this occur in ?
Control of oestrogen synthesis during the early and middle follicular phases:
- GnRH in hypothalamus secreted, stimulating anterior pituitary to secrete FSH and LH
- LH acts on theca cells of follicle, which therefore synthesise androgens (mainly androstenedione)
- Androgens then diffuse across BM to granulosa cells, also surrounding oocytes.
- Then, FSH acts on granulosa cells to convert androgens to estrogens (e.g. androstenedione to oestrodiol 17β), which affects reproductive tract and organs
- Granulosa cells also produce Inhibin
- Inhibin and estrogens have negative feedback effect (Inhibin mainly on FSH, estrogen on FSH, LH, and GnRH)
Control of estrogen synthesis in later follicular phases:
• In the mid-cycle, shift from –ve to +ve feedback.
– Caused by upregulation of receptors (e.g. GnRH in anterior pituitary) when oestrogen plasma levels are rapidly increased (through secretion by dominant follicle).
– Estrogens (and progestins) begin to stimulate increase in GnRH, LH, and FSH
– Results in LH and FSH surge prior to ovulation.
When does LH surge occur ? What is its result ?
At later parts of follicular phase
Increased plasma LH triggers ovulation (resumption of
meiosis) and formation of corpus luteum.
Is inhibin involved in the mid cycle shift from negative to positive feedback ?
No, it performs negative feedback back to FSH regardless of time of cycle
Which type of cell is LH action mediated by, during the later stages of the follicular phase ?
Actions of LH are mediated via granulosa cells (?)
Identify the effects of LH surge on ovarian function.
- The 1° oocyte completes its first meiotic division and undergoes cytoplasmic changes that prepare the ovum for implantation should fertilisation occur. These LH effects on the oocyte are mediated by messengers released from the granulosa cells in response to LH.
- Antrum size (fluid volume) and blood flow to the follicle increase markedly.
- The granulosa cells begin releasing progesterone and decreasing the release of oestrogen, which accounts for the midcycle decrease in plasma oestrogen concentration and the small rise in plasma progesterone just before ovulation.
- Enzymes and prostaglandins, synthesized by the granulosa cells, breakdown the follicular-ovarian membranes. These weakened membranes rupture, allowing the oocyte and its surrounding granulosa cells to be carried into the surface of the ovary.
- The remaining granulosa cells of the ruptured follicle (along with the theca cells of that follicle) are transformed into the corpus luteum, which begins to release progesterone and oestrogen.
Identify the functions of the granulosa cells.
- Nourish oocyte.
- Secrete chemical messengers that influence the oocyte and theca
cells. - Secrete antral fluid.
- Are the site of action for oestrogen and FSH in the control of the follicle development during early and middle follicular phases.
- Express aromatase, which converts androgen (from theca cells) to oestrogen.
- Secrete inhibin, which inhibits FSH secretion via an action on the pituitary.
- Are the site of action for LH induction of changes in the oocyte and follicle culminating in ovulation and formation of the corpus luteum.
Describe the main hormonal events of the luteal phase.
• Suppression of LH and FSH in luteal phase (negative feedback by inhibin to FSH, and by estrogen and progestins to GnRH, FSH, LH)
• If no implantation:
– hCG does not appear in blood
– CL dies
– progesterone and oestrogen decrease
– therefore, menstruation occurs and next MC begins (and FSH and LH increase enough for new follicle growth, thanks to progesterone and estrogen decrease)
• If yes implantation:
Human chorionic gonadotrophin produced by placenta maintains corpus luteum which continues to secrete progesterone. Since progesterone remains high, then levels of LH and FSH will be suppressed and subsequent ovulation will not occur.
What are the main events of the proliferative phase of the uterine cycle ? Identify the hormones involved.
• Menstrual flow ceases.
• Under influence of oestrogen, endometrium thickens.
– Growth of underlying smooth muscle (myometrium) also occurs.
– Also causes the cervical mucus to be readily penetrable by sperm
• Synthesis of receptors for progesterone in endometrial cells also occurs.
• Lasts for ~10 days until ovulation.
Describe the histology of the proliferative phase of the uterine cycle.
- Repair of lining epithelium after menstruation
- Proliferation and thickening of stroma
- Simple test tube shaped glands
- Induction of synthesis of intracellular receptors for progesterone (i.e. it primes the uterus for later progesterone secretion)
- Contractility and excitability of the myometrium increases
- Cervical mucus becomes readily penetrable by sperm (thanks to estrogen)
What are the main events of the secretory phase of the uterine cycle ? Identify the hormones involved.
• Estrogen primed endometrium increases secretory activity under influence of progesterone.
• Endometrial glands:
– become coiled, filled with glycogen, blood vessels become more numerous, enzymes accumulate in glands and connective tissue.
– All to make endometrium a hospital environment for implantation and nourishment of developing embryo.
- Cervical mucus made relatively impenetrable to sperm by progesterone
- Uterine contractions inhibited by progesterone
When does the secretory phase of the uterine cycle begin ?
• Begins soon after ovulation.
Describe the histology of the secretory phase of the uterine cycle.
• Proliferation/thickening of stroma
• Spiral arteries develop alongside complex,
hacksaw shaped glands
• Secretion in the glands is rich in glycoprotein sugars and amino acids
• Enlargement of myometrial cells but depressed overall excitability
