Lecture 15: 81 - Reproduction 3

Question 1

Where is the cumulus oophorus found?

depolymerization of polysaccharides increases/decreases pressure ?

kallman syndrome is a defect in primary/secondary/tertiary function

Answer 1

Graafian Follicle

INCREASES

TERTIARY

Question 2

GnRH from______ n. and _____ area

Inhibited by? (3)

Stimulated by? (1)

How many peptides is GnRH? Where does it stimulate gonadotropes? (ant/post pituitary)

What else does it stimulate which arises from MAGNOCELLULAR neurons?

Answer 2

1. arcuate
2. preoptic
3. dopamine,
4. endorphins,
5. CRH

Norepinephrine stimulates GnRH

decapeptide, anterior pituitary

OXYTOCIN

• Increases uterine contractions (partuition)
• Milk ejection from mammary gland during lactation

Question 3

What happens IN THE CELL
that causes the following for FSH/LH:

1. exocytosis
2. Synthesis

Answer 3

1. Calcium release which causes exocytosis of LH and FSH

2. IP3 and DAG which activate PKC and cause SYNTHESIS of FSH and LH

Question 4

What is the function of FSH?

LH?

FSH and LH have the same ____-subunits but different ____-subunits

Answer 4

1. stimulates follicular envelopment and estradiol secretion
2. promote ovulation & luteinization
3. alpha, beta

Question 5

1. Estrogens from _____
2. Progesterone (progestins) from _____

Are androgens present in the ovary?

4. Androstenedione - testosterone in _____
5. Inhibins and activins (stimulated by _____) feed back at pituitary.

Follistatin binds _____, reducing its effective concentration.

Answer 5

1. follicle
2. corpus luteum

YES
Androgens – small amounts of testosterone, dihydrotestosterone, androstenedione and DHEA.

3. peripheral tissues
4. FSH!!!!
5. activin
   (prevents positive stimulating feedback to pituitary and therefore decreases FSH and LH release to gonads)

Question 6

How did an estrogen receptor ANTAGONIST end up being a leading fertility drug?

Answer 6

Clomiphene (CLOMID)

• Decreased estrogen binding to hypothalamus
• decreased negative feedback,
• increased GnRH pulse frequency
• increased FSH and LH… ovulation.

Question 7

What is clomiphene an example of?

This class also includes tamoxifen, treats hormone-responsive breast cancer

Answer 7

SERM

• selective estrogen receptor modulator
• instead of recruiting coactivators it recruits CO -REPRESSORS
• NO GENE EXPRESSION

Question 8

What are the 3 phases of the menstrual cycle and the main events in each stage?

Which stage is most variable? Which is least?

Answer 8

1. Follicular Phase – time of follicular growth; represents the interval from the onset of menses to ovulation.
   VARIABLE among women
2. Ovulatory “Phase” – Short (1-3 day duration), ** final oocyte maturation and its release into the reproductive tract**
3. Luteal Phase – time of CORPUS LUTEUM FORMATION and the secretion of hormones in preparation for implantation.
   Less variable phase (14 days). **

Question 9

In which part of the cycle does the feedback of estrogen change from negative to positive?

Answer 9

MID - CYCLE!!

OVULATORY PHASE

E2 crosses threshold and causes the LH surge

Question 10

What are the 6 steps in the follicular phase?

1. Hyp. Secretes _____
2. Which releases what?
3. Increase #2
4. What begins to develop as a result? What does this stimulate?
5. ____ and _____ decrease sensitivity of FSH-secreting cells
6. _____ decreases slightly as a result
7. ___ concentration increases past a point

Answer 10

1. GnRH
2. FSH/LH release
3. Increased FSH/LH
4. developing FOLLICLE –> E2

E2 increases follicle

5. E2 AND inhibin have negative feedback on anterior pituitary FSH secreting cells
6. FSH
   - FSH is not completely shut down by estrogen & inhibin
7. E2

Question 11

inhibin B comes from the _______, whereas inhibin A comes predominantly from the ______.

Answer 11

1. dominant follicle
2. corpus luteum
   - Paracrine effect is positive: “inhibin B … augments androgen production by theca cells.”

Question 12

OVULTORY PHASE
state the 6 steps

What crosses threshold?

Surge?

What are the levels of E2 after follicle ruptures?

What plateaus?

What begins making E2 and progesterone?

Answer 12

1. E2 crosses threshold –> POSITIVE FEEDBACK switch
2. LH SURGE
3. Ovulation
4. Rupture of follicle causes decrease in E2
5. Loss of E2 positive feedback = decrease in LH to new PLATEAU
6. Follicle reorganizes into a CORPUS LUTEUM –> makes E2 and progesterone

Question 13

LH surge causes what?

Answer 13

Rupture of follicle!!

Question 14

What are the 5 steps of the luteal phase?

What becomes more dominant?

Negative feedback of what?

What hormones decrease?

What determines if corpus lute degrades?

Why does the endometrium degrade if no fertilization?

Answer 14

1. Corpus lute becomes more dominant –> makes E2 and a lot of progesterone
2. strong negative feedback of progesterone, and E2 inhibitory!!
3. Decreased FSH/LH/GnRH
4. Loss of LH will cause the corpus luteum to degrade unless it is “rescued” by implantation of fertilized embryo –> HCG
5. Absent HCG and LH = E2 and progesterone decrease, endometrium degrades

–> bleeding indicates beginning of next phase

Question 15

How does a pregnancy test work?

Answer 15

pregnancy test

= ELISA –> detects antibodies that bind to hCG ***

Question 16

What hormone increases slightly at the end of the FOLLICULAR PHASE? What is the purpose of this?

Answer 16

1. Testosterone

2. Increase libido

Question 17

What 3 important results arise due to the LH surge?

What may augment the LH surge and lead to an FSH surge?

What is the importance of the MID CYCLE FSH surge?

Answer 17

1. switches estradiol action from NEGATIVE to POSITIVE
2. increases density of GnRH receptors
3. converts the stored LH pool of vesicles to “readily releasable”

Small rise in progesterone

** important to activate a cohort of new follicles for the next cycle**

Question 18

During menses, why are estradiol and progesterone levels low? (2)

What begins to rise because of lack of negative feedback?

The sudden withdrawal of _____ leads to sloughing of functional endometrial layer.

Answer 18

1. regression of the corpus luteum
2. because the new follicles are immature

FSH!!

steroids

Question 19

What drives the surge mode of LH that is unique to females ? (tonic in males)

How is estrogen dose, time course, and prior hormonal status dependent?

Answer 19

• circulating levels of ovarian STEROIDS

Estrogens – depending on the dose, time course and prior hormonal status can inhibit or stimulated LH secretion

Question 20

When does pulsatile LH release develop?**

What matures and what is the result?

What happens to LH and FSH levels post-menopause?

Which is higher, FSH or LH?

Answer 20

1. after puberty (only surges at night)**
2. hypothalamic “surge center” matures which leads to pulsatile release of GnRH and thus LH, FSH, and estrogen
3. LH and FSH are HIGH with high use frequency
   - since no negative feedback due to non-functioning ovaries

FSH is greater than LH

Question 21

Primordial & Primary FOllicle:

_______ are required for development from primordial to primary.

If estrogen levels are too low (as with 17-hydroxylase deficiency) what happens?

Answer 21

1. Gonadotropins
   - no ovarian receptors for LH/FSH (“resistant ovarian syndrome”) results in primordial follicle without any primary follicles.
2. primordial follicles do NOT develop into primary follicles.

Question 22

SECONDARY follicles

To make this follicle type, the ____ cells proliferate and develop LH receptors.

_____ cells acquire receptors for FSH, androgens and estrogens

Development of antrum occurs in response to what?

____ drives proliferation of granulosa cells, and increases FSH and LH receptors on granulosa cells

Answer 22

1. theca
2. Granulosa

**Follicle becomes a steroid producing unit. ( secondary follicle)

3. response to FSH and estradiol
4. FSH

Question 23

Graafian Follicles:

____ and _____ are required for mitosis. (granulosa cells)

FSH, LH and estradiol required for maximal _____ production.

What is required for normal growth and development ?

Premature exposure to ____ inhibits mitosis and steroidogenesis.

OR

___&____too early

Answer 23

1. FSH
2. estradiol
3. progesterone
4. A certain sequence of FSH, Estradiol and LH at the correct concentration
5. LH!!!!!
6. Estradiol/Progesterone

Question 24

The following are actions of what?

1. Inhibit growth of cohort follicles
2. Alter cervical mucus
3. Fallopian tube motility favoring transport of ovum and zygote
4. Prime GnRH action on LH secretion to evoke ovulatory urge of LH
5. Prepare uterine endometrium for progesterone to evoke secretory response

Answer 24

ESTROGENS

Question 25

What is the two compartment theory of Graafian Follicle Steroidogenesis? What cell produces AROMATASE? What cells are stimulated by LH and are responsible for covering cholesterol to testosterone? Which cells are vascularized?

Answer 25

Varying functions of Granulosa cells vs. Theca Cells GRANULOSA cells - make progesterone and pregnenolone - do NOT convert 21 carbon to 19 carbon androgens THECA cells make testosterone but have NO aromatase to convert it to estradiol ** VASCULARIZED***

Question 26

Which cells are responsible for steroidogenesis? For estradiol?

Answer 26

1. Theca | 2. Granulosa

Question 27

Hormonal control of corpus lute: Increased ____ receptors due to FSH actions in follicular phase LH converts granulosa and theca cells to _____make abundant progesterone and estradiol Corpus Luteum has finite life span – luteolysis occurs 9-10 days after formation unless rescued by _______ produced by developing embryo

Answer 27

1.LH 2. lutein cells - Progesterones formed faster than can be processed 3. human chorionic gonadotropin

Question 28

What do the proliferative, secretory, and ischemic phases describe?

Answer 28

ENDOMETRIAL FUNCTIONS | - rather than ovulatory functions

Question 29

PROLIFERATIVE phase of endometrium is dominated by what hormone? What does it coincide with? What 2 important things occur? What receptors increase? (2)

Answer 29

1. Estradiol 2. Coincides with mid- to late-follicular phase a) . Thickening of stromal and endothelial layers b) Vascularization and development of spiral arteries 3 Progesterone and Estrogen receptors

Question 30

The SECRETORY phase of endometrium is dominated by what hormone? What does it concede with in ovulation? What increases? What do endometrial glands do? What happens to the stroma?

Answer 30

PROGESTERONE 2. Proliferation to secretion 3. Vascularization increases, glycogen content 4. Endometrial glands secrete large amounts of CARB RICH mucus and become engorged with secretion 5. Stroma becomes edematous

Question 31

What declines in the ISCHEMIC phase? (menstrual)? 1. Low levels of what 2 hormones? 2. What happens to spiral arteries? 3. Increase in what enzymes?

Answer 31

1. PROGESTERONE 2. Shift is from proliferation to secretion 3. Nucleolar channel system 4. Vascularization increases, glycogen content increases 5. Endometrial glands secrete large amounts of carbohydrate-rich mucus, become engorged with secretions 6. Stroma becomes edematous

Question 32

Estrogen in the follicular phase does what to the cervical mucus? What pattern is visible? What is the purpose of this? Primitive test for _____

Answer 32

Estrogen action in follicular phase – increasing the quantity, alkalinization, and viscosity (thinning of mucous) 2. Ferning 3. Changes promote survival and transport of sperm 4. Primitive test for ovulation

Question 33

What happens to vaginal epithelial cells during the mid to late follicular phase as estrogens increase? What hormone dominates in luteal phase?

Answer 33

Vaginal epithelial cells become large, squamous, cornified with small or absent nuclei Progesterone

Question 34

What happens during menopause? Consequences?

Answer 34

Loss of negative feed back from ESTRADIOL and INHIBIN cause 3-4 fold increase in FSH and LH with FSH>LH. Pulsatile secretion remains without cyclicity. 1. osteoporosis 2. CV disease 3. Thinning of vaginal epithelium 4. Decreased breast mass 5. Vascular flushing This leads to periodic increases in core temperature, causing reflex vasodilation, sweating, and increased pulse rate.

Question 35

What is the result of treating with hormone replacement? Why was this study called into question?

Answer 35

Increased risks, except for osteoporosis Estrogen and progesterone used in WHI were not good replacements. (ex: estrone from horses) The WHI didn’t separate various stages of menopause. 1. Women who received HT during peri-menopause had most beneficial outcomes. DURING MENOPAUSE = BEST 2. Women who received HT >10 yrs. Post-menopause had most detrimental outcomes.

Question 36

What is the "Timing hypothesis"

Answer 36

There is a window of opportunity for hormone replacement in peri-menopausal women (however, TX worsens the risks once menopause has already occurred)