Sex Steroid Hormones

Question 1

Where is GnRH released from?

Answer 1

The hypothalamus

Question 2

What is the effect of GnRH?

Answer 2

Stimulates the synthesis and secretion of LH and FSH

Question 3

Where is FSH released from?

Answer 3

The anterior pituitary

Question 4

What is the effect of FSH?

Answer 4

Stimulates follicle growth and occyte maturation

Question 5

Where is LH released from?

Answer 5

Anterior pituitary

Question 6

What is the function of LH?

Answer 6

• Stimulates ovulation
• Causes the ruptured follicle to become the corpus luteum

Question 7

Where is oestrogen released from?

Answer 7

Maturing follicle

Question 8

What is the effect of oestrogen?

Answer 8

• It stimulates repair and growth of the endometrium
• Feedback inhibitor for FSH and LH

Question 9

Where is progesterone released from?

Answer 9

Corpus luteum

Question 10

What is the effect of progesterone?

Answer 10

• Prepares endometrium for implantation
• Promotes growth of mammary glands
• Feedback inhibitor for FSH and LH

Question 11

Draw a diagram illustrating the feedback mechanism involved in reproductive hormones

Answer 11

Question 12

How are sex steroid hormones transported?

Answer 12

Bound to SHBG (except progesterone) and albumin

Question 13

What % of the sex hormones are free in the plasma?

Answer 13

1-2%

Question 14

How is SHBG production regulated?

Answer 14

It is upregulated by oestrogen

Question 15

What does SHBG binding to sex hormones protect against?

Answer 15

Hepatic metabolism - the binding prevents entry to the liver

Question 16

Describe the liver metabolism of progesterone

Answer 16

It is almost totally metabolised in one passage through the liver in the first pass effect

Question 17

What effect does storage of sex hormones have on the half life?

Answer 17

It increases it

Question 18

Where can sex steroid hormones be easily stored?

Answer 18

In fatty tissue - adipocytes and brain

Question 19

Why can sex steroids be easily stored in fatty tissue?

Answer 19

Because they are lipophilic

Question 20

How are sex steroid hormones stored in fatty tissues?

Answer 20

They complex into the plasma membrane just like cholesterol

Question 21

Does the complexing of sex steroid hormones into the membrane affect membrane fluidity?

Answer 21

Yes

Question 22

How are the metabolites of sex steroid hormones excreted?

Answer 22

• In faeces as glucuronides
• In urine as sulphates

Question 23

Why must the glucuronide from sex hormone metabolism be excreted in faeces?

Answer 23

As the molecule is too big to cross the plasma membrane, and so it passes into the bile duct

Question 24

How are the sulphates produced from sex hormone metabolism excreted in urine?

Answer 24

They get ionised, pass through the body in the plasma, and then get picked up by clatherin coated pits in the kidney

Question 25

How do sex steroid hormones exert their effects?

Answer 25

Through binding to nuclear receptors

Question 26

What are the types of oestrogen receptors?

Answer 26

ER-alpha and ER-beta ## Footnote *Truncated forms exist in cancer*

Question 27

What are the types of progesterone receptors?

Answer 27

PR-A and PR-B, *although another 3 isoforms may exist*

Question 28

What are the receptors for androgens?

Answer 28

AR-1 and AR-2, *although membrane forms exist in prostate cancer*

Question 29

How do the molecular structures of the receptors for the sex hormones compare to one another?

Answer 29

They are very similar

Question 30

How are the molecular structures for the different sex hormone receptor generated?

Answer 30

From different genes on different chromosomes

Question 31

How are the PR and AR isoforms generated?

Answer 31

By alternative splicing

Question 32

What are the sex steroid hormone related drug groups?

Answer 32

* Sex steroid hormones * Inhibitors and antagonists * Mixed agonists/antagonists

Question 33

Give 4 sex steroid hormone inhibitors/antagonist drugs

Answer 33

* Clomiphene * Mifepristone (RU486) * Finasteride * Tamoxifen

Question 34

Give two sex steroid hormone mixed agonists/antagonist drugs

Answer 34

* Selective oestrogen receptor molecules (SERMs) * Selective progesterone receptor modulators (SPRMs)

Question 35

Do SARMs exist?

Answer 35

Yes, but they are only, and rarely, used in the treatment of women with PCOS

Question 36

What are the major effects of oestradiol?

Answer 36

* Stimulates growth of endometrium and breast * Stimulates production of PR

Question 37

What are the major effects of progesterone?

Answer 37

* Stimulates growth of the endometrium and breast * Maintains pregnancy * Inhibits production of ER

Question 38

What are the major effects of testosterone?

Answer 38

* Stimulates male characteristics * Hairy body * Deep voice * Anabolism * Aggression

Question 39

What are sex steroid hormones synthesised from?

Answer 39

Cholesterol

Question 40

What are the potential therapeutic effects of oestrogen?

Answer 40

* Mildly anabolic * Sodium and water retention * Raises HDL and lowers LDL * Decreases bone reabsorption * Impairs glucose tolerance * Increases blood coagulability * *Improves mood* * *Improves concentration* * *Reduces risk of Alzheimers disease*

Question 41

What are the side effects of oestrogen therapy?

Answer 41

* Breast tenderness * Nausea * Vomiting * Water retention * Increased blood coaguability * Thromboembolism * Impaired glucose tolerance * Endometrial hyperplasia and cancer * Ovarian metaplasia and cancer * Breast hyperplasia and cancer

Question 42

What are the potentially therapeutic actions of progesterone?

Answer 42

* Anabolic * Increases bone mineral density * Fluid retention * Mood changes * Maintains pregnancy

Question 43

What are the side effects of PMS?

Answer 43

* Weight gain * Fluid retention * Anabolic * Acne * Nausea/vomiting * Irritability * Depression, PMS * Lack of concentration

Question 44

What are the potentially therapeutic effects of testosterone?

Answer 44

* Inducing male secondary sex characteristics * Anabolic

Question 45

What are the side effects of testoesterone?

Answer 45

* Acne * Increases aggression * Has adverse effects of lipid profiles, particularly the HDL-C/LDL-C ratio

Question 46

What does the effect of testosterone on lipid profiles account for?

Answer 46

The increased risk of atherosclerotic disease in males and gender reassigned females

Question 47

What are the sex steroid hormone inhibitors and antagonists?

Answer 47

Weak oestrogens that block receptors

Question 48

What is clomiphene used for?

Answer 48

Ovulation induction

Question 49

How does clomiphene induce ovulation?

Answer 49

It inhibits oestrogen binding to its ER in the anterior pituitary, and therefore inhibits negative feedback, resulting in increased FSH and LH expression

Question 50

What is the use of tamoxifen?

Answer 50

It reduces the risk of breast cancer

Question 51

How does tamoxifen reduce the risk of breast cancer?

Answer 51

Binds to ER in breast tissue and blocks oestrogen-stimulated myoepithelial cell division

Question 52

What is mifepristone used for?

Answer 52

* Medical termination of pregnancy * Induction of labour

Question 53

What does mifepristone do?

Answer 53

* It is a partial agonists to the progesterone receptor, and inhibits progesterone action * Sensitises uterus to prostaglandins

Question 54

Give an example of an anti-androgen

Answer 54

Cyproterone

Question 55

What is cyproterone a derivative of?

Answer 55

Progesterone

Question 56

What effect does cyproterone have?

Answer 56

It has a weak progestogenic effect, as it is a partial agonist at the progesterone receptor, and so competes with dihydrotestosterone

Question 57

Where is cyproterone used?

Answer 57

In the combined oral contraceptive pill

Question 58

Give an example of a SERM?

Answer 58

Raloxifene

Question 59

What effect does raloxifene have?

Answer 59

Oestrogen effects on bone, lipid metabolism, and blood coagulation

Question 60

What are the advantages of raloxifene?

Answer 60

* Protects against osteoporosis * No proliferative effects on endometrium and breast * Reduced risk of invasive breast cancer in post-menopausal women with osteoporosis

Question 61

What are the disadvantages of raloxifene?

Answer 61

Increases hot flushes and sweating

Question 62

Give 5 drugs used in androgen replacement therapy

Answer 62

* Testosterone * Enenthate * Proprionate * Undecanoate * Mesterolone

Question 63

How can androgen replacement therapies be administered?

Answer 63

* Implants * IM * Oral

Question 64

What are the uses of androgen replacement therapy?

Answer 64

* Prevents hair loss, and so used in treatment of male pattern baldness * Used in treatment of benign prostatic hypertrophy

Question 65

Why is finasteride not approved for use in women?

Answer 65

Due to risks of birth defects in a fetus