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BIOM2010 > Reproductive Endocrinology > Flashcards

Reproductive Endocrinology Flashcards

1
Q

Define GnRH

A

Gonadotrophin releasing hormone

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2
Q

Where does GnRH act?

A

On the gonadotroph cells of the anterior pituitary

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3
Q

What does the gonadotroph cell secrete?

A

LH and FSH

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4
Q

Which of LH and FSH has a pulsatile secretion pattern?

A

LH

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5
Q

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

A

LH

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6
Q

Define Kallmans syndrome

A

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

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7
Q

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

A

True

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8
Q

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

A

Follicular stage

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9
Q

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

A

Estrogen

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10
Q

Explain the role of granulosa cells

A

They secrete inhibin

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11
Q

Define corpus luteum and its role

A

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

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12
Q

Where does inhibin act?

A

Acts on the anterior pituitary to reduce FSH secretion

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13
Q

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

A

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

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14
Q

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

A

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

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15
Q

In which two cells does the estrogen synthesis pathway occur?

A

Theca and granulosa cells

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16
Q

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

A

LH

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17
Q

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

A

FSH

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18
Q

Where does inhibin feedback to?

A

Anterior pituitary

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19
Q

Why is FSH needed after menstruation?

A

To stimulate estrogen production in the granulosa cells

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20
Q

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

A

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

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21
Q

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

A

LH and FSH

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22
Q

Explain the negative feedback involving progesterone

A

It inhibits the positive feedback of estrogen

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23
Q

Explain the role of progesterone in the uterus

A

Stimulates secretory and vascular activity of the endometrium preparing for implantation

24
Q

When does estrogen negative feedback occur

A

During the follicular stage when estrogen levels are low

25
Q

When does estrogen positive feedback occur

A

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

26
Q

What does a surge in LH cause?

A

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

27
Q

FSH action?

A

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

28
Q

Define menopause

A

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

29
Q

Explain negative feedback in menopause

A

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

30
Q

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

A

Causes hyperproliferation, increasing risk of cancer

31
Q

Compare ethinylestradiol and estradiol

A

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

32
Q

Explain use of estrogen in HRT

A

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

33
Q

What is levonorgestrel

A

Synthetic progesterone

34
Q

Explain how the pill affects FSH

A

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

35
Q

Explain how the pill affects LH

A

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

36
Q

Explain the action of progesterone in the pill

A

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

37
Q

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

A

Because estrogen promotes blood clotting

38
Q

Compare the concentration of levonorgestrel in Levonelle compared to regular pill

A 
Regular = 0.15mg
Levonelle = 1.5mg
39
Q

Explain the MOA of Levonelle

A

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

40
Q

Compare EllaOne to Levonelle

A

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

41
Q

What is the active ingredient in EllaOne

A

Ulipristal

42
Q

What is mifepristone used for?

A

Pregnancy termination

43
Q

Explain the MOA of mifepristone

A

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

44
Q

What other pill needs to be given with mifepristone?

A

A prostaglandin pill. This induces uterine contractions

45
Q

Explain the goal of therapy for estrogen dependent cancers

A

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

46
Q

Which reaction does aromatase catalyse?

A

The conversion of androgens (like testosterone) into estradiol

47
Q

Describe the MOA of letrozole or anastrozole

A

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

48
Q

Name 2 aromatase inhibitors

A

Letrozole and anastrozole

49
Q

Define ERE and its action

A

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.

50
Q

What happens once estrogen passively diffuses into a cell?

A

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

51
Q

What is the drug tamoxifen used for?

A

Estrogen dependent cancers

52
Q

Tamoxifen is activated by the liver to form what compound?

A

4-OH-Tam

53
Q

Explain the MOA of tamoxifen / 4-OH-TAM

A

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

54
Q

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

A

Increases the risk of endometrial cancer

55
Q

Benefits of tamoxifen?

A

Slows the growth of breast cancer

BIOM2010 (12 decks)

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