Reproductive Endocrinology

Question 1

Define GnRH

Answer 1

Gonadotrophin releasing hormone

Question 2

Where does GnRH act?

Answer 2

On the gonadotroph cells of the anterior pituitary

Question 3

What does the gonadotroph cell secrete?

Answer 3

LH and FSH

Question 4

Which of LH and FSH has a pulsatile secretion pattern?

Answer 4

LH

Question 5

Release of GnRH is pulsatile but cannot be measured in the blood. What is measured instead?

Answer 5

LH

Question 6

Define Kallmans syndrome

Answer 6

Genetic defect resulting in no GnRH neurons in the hypothalamus. Results in reduced levels of sex hormones, no puberty and underdevelooment of gonads

Question 7

True of false. GnRH agonists can be used to suppress ovulation

Answer 7

True

Question 8

Release of LH is more rapid but of smaller amplitude during which phase of the cycle?

Answer 8

Follicular stage

Question 9

FSH works with —? To stimulate the proliferation of granulosa cells

Answer 9

Estrogen

Question 10

Explain the role of granulosa cells

Answer 10

They secrete inhibin

Question 11

Define corpus luteum and its role

Answer 11

It is a temporary stage of the egg once ovulation has occurs. It secretes progesterone in preparation for pregnancy

Question 12

Where does inhibin act?

Answer 12

Acts on the anterior pituitary to reduce FSH secretion

Question 13

Why is it important that inhibin is secreted to reduce FSH secretion?

Answer 13

Because too much FSH would mean too much follicle maturation which would be a waste

Question 14

Once the corpus luteum is formed, which hormones go up and which go down?

Answer 14

Inhibin and progesterone go up, which causes LH and FSH to go down

Question 15

In which two cells does the estrogen synthesis pathway occur?

Answer 15

Theca and granulosa cells

Question 16

Cholesterol uptake and androgen synthesis in theca cells is stimulated by which hormone?

Answer 16

LH

Question 17

The conversion of androgens into estradiol in the granulosa cell is stimulated by which hormone?

Answer 17

FSH

Question 18

Where does inhibin feedback to?

Answer 18

Anterior pituitary

Question 19

Why is FSH needed after menstruation?

Answer 19

To stimulate estrogen production in the granulosa cells

Question 20

What Happens to hormone levels as the corpus luteum dies off?

Answer 20

Inhibin secretion is reduced which increases FSH levels ready for the next follicular stage

Question 21

If estrogen levels are low, which hormones do you want to increase?

Answer 21

LH and FSH

Question 22

Explain the negative feedback involving progesterone

Answer 22

It inhibits the positive feedback of estrogen

Question 23

Explain the role of progesterone in the uterus

Answer 23

Stimulates secretory and vascular activity of the endometrium preparing for implantation

Question 24

When does estrogen negative feedback occur

Answer 24

During the follicular stage when estrogen levels are low

Question 25

When does estrogen positive feedback occur

Answer 25

Towards the end of the cycle, when estrogen levels are high. Positive feedback = ovulation. Purpose of positive feedback is to stimulate the release of more LH and FSH, leading to the production of more estrogen

Question 26

What does a surge in LH cause?

Answer 26

Triggers ovulation. LUTEINIZING hormone turns the follicle into the corpus luteum

Question 27

FSH action?

Answer 27

Stimulates growth and maturation of eggs (follicles) during the follicular phase

Question 28

Define menopause

Answer 28

Where the remaining follicles no longer respond to FSH. Results in reduced levels of estrogen and progesterone and no development of the endometrial lining

Question 29

Explain negative feedback in menopause

Answer 29

Low estrogen levels causes negative feedback with the goal of trying to increase estrogen. GnRH, LH and FSH levels rise

Question 30

In the absence of progestins (synthetic progesterone), what does estrogen do to the endometrium?

Answer 30

Causes hyperproliferation, increasing risk of cancer

Question 31

Compare ethinylestradiol and estradiol

Answer 31

Estradiol is the endogenous estrogen. It is more potent than the modified ethinylestradiol, but not as orally active

Question 32

Explain use of estrogen in HRT

Answer 32

Exogenous estrogen in HRT is used to induce negative feedback, meaning levels of GnRH, FSH and LH are reduced. This relieves many of the Sx

Question 33

What is levonorgestrel

Answer 33

Synthetic progesterone

Question 34

Explain how the pill affects FSH

Answer 34

High levels of estrogen due to the pill induce negative feedback and inhibit the secretion of FSH, meaning no follicle maturation and ovulation occurs

Question 35

Explain how the pill affects LH

Answer 35

Increased estrogen and progesterone levels inhibit the synthesis of LH due to negative feedback. This means the surge of LH required for ovulation does not occur

Question 36

Explain the action of progesterone in the pill

Answer 36

Thickens the cervical mucus which helps prevent sperm from getting in to uterus

Question 37

Why should patients with a history of HT, stroke or DVT use the progestin only pill?

Answer 37

Because estrogen promotes blood clotting

Question 38

Compare the concentration of levonorgestrel in Levonelle compared to regular pill

Answer 38

``` Regular = 0.15mg Levonelle = 1.5mg ```

Question 39

Explain the MOA of Levonelle

Answer 39

Prevents the LH surge by inducing the negative feedback of progesterone. Only works if taken before this surge occurs

Question 40

Compare EllaOne to Levonelle

Answer 40

EllaOne inhibits progesterone from binidng to its receptors, which prevents or delays ovulation. Levonelle works by increasing progesterone to induce negative feedback

Question 41

What is the active ingredient in EllaOne

Answer 41

Ulipristal

Question 42

What is mifepristone used for?

Answer 42

Pregnancy termination

Question 43

Explain the MOA of mifepristone

Answer 43

Causes a breakdown of the decidua- the endometrium lining formed in preparation for pregnancy

Question 44

What other pill needs to be given with mifepristone?

Answer 44

A prostaglandin pill. This induces uterine contractions

Question 45

Explain the goal of therapy for estrogen dependent cancers

Answer 45

The goal is to either block estrogen synthesis, or block it from binding to its receptor

Question 46

Which reaction does aromatase catalyse?

Answer 46

The conversion of androgens (like testosterone) into estradiol

Question 47

Describe the MOA of letrozole or anastrozole

Answer 47

They are competitive antagonists for the androgen binding site on the aromatase enzyme

Question 48

Name 2 aromatase inhibitors

Answer 48

Letrozole and anastrozole

Question 49

Define ERE and its action

Answer 49

Estrogen responsive element. This is the segment of DNA that the estrogen dimer binds to, which causes a conformational change which allows coactivators to bind to DNA and cause gene transcription.

Question 50

What happens once estrogen passively diffuses into a cell?

Answer 50

It binds to the intracellular receptor. Once bound, the receptor undergoes a conformational change which allows it to form a dimer with another estrogen-bound estrogen receptor. It can then enter the nucleus

Question 51

What is the drug tamoxifen used for?

Answer 51

Estrogen dependent cancers

Question 52

Tamoxifen is activated by the liver to form what compound?

Answer 52

4-OH-Tam

Question 53

Explain the MOA of tamoxifen / 4-OH-TAM

Answer 53

It enters the cell and competes for binding to the estrogen receptor. Once bound, it forms a dimer with another estrogen receptor bound to 4-OH-Tam. The dimer then enters the nucleus, binds to ERE but does not cause a conformational change, meaning no gene transcription occurs

Question 54

With long term use, what is one serious issue with tamoxifen

Answer 54

Increases the risk of endometrial cancer

Question 55

Benefits of tamoxifen?

Answer 55

Slows the growth of breast cancer