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5: Y5 - ESA 5 - Pharmacology > Sex Steroid Hormones > Flashcards

Sex Steroid Hormones Flashcards

1
Q

Where is GnRH released from?

A

The hypothalamus

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2
Q

What is the effect of GnRH?

A

Stimulates the synthesis and secretion of LH and FSH

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3
Q

Where is FSH released from?

A

The anterior pituitary

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4
Q

What is the effect of FSH?

A

Stimulates follicle growth and occyte maturation

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5
Q

Where is LH released from?

A

Anterior pituitary

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6
Q

What is the function of LH?

A
  • Stimulates ovulation
  • Causes the ruptured follicle to become the corpus luteum
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7
Q

Where is oestrogen released from?

A

Maturing follicle

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8
Q

What is the effect of oestrogen?

A
  • It stimulates repair and growth of the endometrium
  • Feedback inhibitor for FSH and LH
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9
Q

Where is progesterone released from?

A

Corpus luteum

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10
Q

What is the effect of progesterone?

A
  • Prepares endometrium for implantation
  • Promotes growth of mammary glands
  • Feedback inhibitor for FSH and LH
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11
Q

Draw a diagram illustrating the feedback mechanism involved in reproductive hormones

A
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12
Q

How are sex steroid hormones transported?

A

Bound to SHBG (except progesterone) and albumin

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13
Q

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

A

1-2%

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14
Q

How is SHBG production regulated?

A

It is upregulated by oestrogen

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15
Q

What does SHBG binding to sex hormones protect against?

A

Hepatic metabolism - the binding prevents entry to the liver

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16
Q

Describe the liver metabolism of progesterone

A

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

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17
Q

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

A

It increases it

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18
Q

Where can sex steroid hormones be easily stored?

A

In fatty tissue - adipocytes and brain

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19
Q

Why can sex steroids be easily stored in fatty tissue?

A

Because they are lipophilic

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20
Q

How are sex steroid hormones stored in fatty tissues?

A

They complex into the plasma membrane just like cholesterol

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21
Q

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

A

Yes

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22
Q

How are the metabolites of sex steroid hormones excreted?

A
  • In faeces as glucuronides
  • In urine as sulphates
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23
Q

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

A

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

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24
Q

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

A

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

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25
Q

How do sex steroid hormones exert their effects?

A

Through binding to nuclear receptors

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26
Q

What are the types of oestrogen receptors?

A

ER-alpha and ER-beta

Truncated forms exist in cancer

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27
Q

What are the types of progesterone receptors?

A

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

28
Q

What are the receptors for androgens?

A

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

29
Q

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

A

They are very similar

30
Q

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

A

From different genes on different chromosomes

31
Q

How are the PR and AR isoforms generated?

A

By alternative splicing

32
Q

What are the sex steroid hormone related drug groups?

A
  • Sex steroid hormones
  • Inhibitors and antagonists
  • Mixed agonists/antagonists
33
Q

Give 4 sex steroid hormone inhibitors/antagonist drugs

A
  • Clomiphene
  • Mifepristone (RU486)
  • Finasteride
  • Tamoxifen
34
Q

Give two sex steroid hormone mixed agonists/antagonist drugs

A
  • Selective oestrogen receptor molecules (SERMs)
  • Selective progesterone receptor modulators (SPRMs)
35
Q

Do SARMs exist?

A

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

36
Q

What are the major effects of oestradiol?

A
  • Stimulates growth of endometrium and breast
  • Stimulates production of PR
37
Q

What are the major effects of progesterone?

A
  • Stimulates growth of the endometrium and breast
  • Maintains pregnancy
  • Inhibits production of ER
38
Q

What are the major effects of testosterone?

A
  • Stimulates male characteristics
  • Hairy body
  • Deep voice
  • Anabolism
  • Aggression
39
Q

What are sex steroid hormones synthesised from?

A

Cholesterol

40
Q

What are the potential therapeutic effects of oestrogen?

A
  • 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
41
Q

What are the side effects of oestrogen therapy?

A
  • 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
42
Q

What are the potentially therapeutic actions of progesterone?

A
  • Anabolic
  • Increases bone mineral density
  • Fluid retention
  • Mood changes
  • Maintains pregnancy
43
Q

What are the side effects of PMS?

A
  • Weight gain
  • Fluid retention
  • Anabolic
  • Acne
  • Nausea/vomiting
  • Irritability
  • Depression, PMS
  • Lack of concentration
44
Q

What are the potentially therapeutic effects of testosterone?

A
  • Inducing male secondary sex characteristics
  • Anabolic
45
Q

What are the side effects of testoesterone?

A
  • Acne
  • Increases aggression
  • Has adverse effects of lipid profiles, particularly the HDL-C/LDL-C ratio
46
Q

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

A

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

47
Q

What are the sex steroid hormone inhibitors and antagonists?

A

Weak oestrogens that block receptors

48
Q

What is clomiphene used for?

A

Ovulation induction

49
Q

How does clomiphene induce ovulation?

A

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

50
Q

What is the use of tamoxifen?

A

It reduces the risk of breast cancer

51
Q

How does tamoxifen reduce the risk of breast cancer?

A

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

52
Q

What is mifepristone used for?

A
  • Medical termination of pregnancy
  • Induction of labour
53
Q

What does mifepristone do?

A
  • It is a partial agonists to the progesterone receptor, and inhibits progesterone action
  • Sensitises uterus to prostaglandins
54
Q

Give an example of an anti-androgen

A

Cyproterone

55
Q

What is cyproterone a derivative of?

A

Progesterone

56
Q

What effect does cyproterone have?

A

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

57
Q

Where is cyproterone used?

A

In the combined oral contraceptive pill

58
Q

Give an example of a SERM?

A

Raloxifene

59
Q

What effect does raloxifene have?

A

Oestrogen effects on bone, lipid metabolism, and blood coagulation

60
Q

What are the advantages of raloxifene?

A
  • Protects against osteoporosis
  • No proliferative effects on endometrium and breast
  • Reduced risk of invasive breast cancer in post-menopausal women with osteoporosis
61
Q

What are the disadvantages of raloxifene?

A

Increases hot flushes and sweating

62
Q

Give 5 drugs used in androgen replacement therapy

A
  • Testosterone
  • Enenthate
  • Proprionate
  • Undecanoate
  • Mesterolone
63
Q

How can androgen replacement therapies be administered?

A
  • Implants
  • IM
  • Oral
64
Q

What are the uses of androgen replacement therapy?

A
  • Prevents hair loss, and so used in treatment of male pattern baldness
  • Used in treatment of benign prostatic hypertrophy
65
Q

Why is finasteride not approved for use in women?

A

Due to risks of birth defects in a fetus

5: Y5 - ESA 5 - Pharmacology (28 decks)

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