Sex Steroid Hormones Flashcards
Where is GnRH released from?
The hypothalamus
What is the effect of GnRH?
Stimulates the synthesis and secretion of LH and FSH
Where is FSH released from?
The anterior pituitary
What is the effect of FSH?
Stimulates follicle growth and occyte maturation
Where is LH released from?
Anterior pituitary
What is the function of LH?
- Stimulates ovulation
- Causes the ruptured follicle to become the corpus luteum
Where is oestrogen released from?
Maturing follicle
What is the effect of oestrogen?
- It stimulates repair and growth of the endometrium
- Feedback inhibitor for FSH and LH
Where is progesterone released from?
Corpus luteum
What is the effect of progesterone?
- Prepares endometrium for implantation
- Promotes growth of mammary glands
- Feedback inhibitor for FSH and LH
Draw a diagram illustrating the feedback mechanism involved in reproductive hormones
How are sex steroid hormones transported?
Bound to SHBG (except progesterone) and albumin
What % of the sex hormones are free in the plasma?
1-2%
How is SHBG production regulated?
It is upregulated by oestrogen
What does SHBG binding to sex hormones protect against?
Hepatic metabolism - the binding prevents entry to the liver
Describe the liver metabolism of progesterone
It is almost totally metabolised in one passage through the liver in the first pass effect
What effect does storage of sex hormones have on the half life?
It increases it
Where can sex steroid hormones be easily stored?
In fatty tissue - adipocytes and brain
Why can sex steroids be easily stored in fatty tissue?
Because they are lipophilic
How are sex steroid hormones stored in fatty tissues?
They complex into the plasma membrane just like cholesterol
Does the complexing of sex steroid hormones into the membrane affect membrane fluidity?
Yes
How are the metabolites of sex steroid hormones excreted?
- In faeces as glucuronides
- In urine as sulphates
Why must the glucuronide from sex hormone metabolism be excreted in faeces?
As the molecule is too big to cross the plasma membrane, and so it passes into the bile duct
How are the sulphates produced from sex hormone metabolism excreted in urine?
They get ionised, pass through the body in the plasma, and then get picked up by clatherin coated pits in the kidney
How do sex steroid hormones exert their effects?
Through binding to nuclear receptors
What are the types of oestrogen receptors?
ER-alpha and ER-beta
Truncated forms exist in cancer
What are the types of progesterone receptors?
PR-A and PR-B, although another 3 isoforms may exist
What are the receptors for androgens?
AR-1 and AR-2, although membrane forms exist in prostate cancer
How do the molecular structures of the receptors for the sex hormones compare to one another?
They are very similar
How are the molecular structures for the different sex hormone receptor generated?
From different genes on different chromosomes
How are the PR and AR isoforms generated?
By alternative splicing
What are the sex steroid hormone related drug groups?
- Sex steroid hormones
- Inhibitors and antagonists
- Mixed agonists/antagonists
Give 4 sex steroid hormone inhibitors/antagonist drugs
- Clomiphene
- Mifepristone (RU486)
- Finasteride
- Tamoxifen
Give two sex steroid hormone mixed agonists/antagonist drugs
- Selective oestrogen receptor molecules (SERMs)
- Selective progesterone receptor modulators (SPRMs)
Do SARMs exist?
Yes, but they are only, and rarely, used in the treatment of women with PCOS
What are the major effects of oestradiol?
- Stimulates growth of endometrium and breast
- Stimulates production of PR
What are the major effects of progesterone?
- Stimulates growth of the endometrium and breast
- Maintains pregnancy
- Inhibits production of ER
What are the major effects of testosterone?
- Stimulates male characteristics
- Hairy body
- Deep voice
- Anabolism
- Aggression
What are sex steroid hormones synthesised from?
Cholesterol
What are the potential therapeutic effects of oestrogen?
- 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
What are the side effects of oestrogen therapy?
- 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
What are the potentially therapeutic actions of progesterone?
- Anabolic
- Increases bone mineral density
- Fluid retention
- Mood changes
- Maintains pregnancy
What are the side effects of PMS?
- Weight gain
- Fluid retention
- Anabolic
- Acne
- Nausea/vomiting
- Irritability
- Depression, PMS
- Lack of concentration
What are the potentially therapeutic effects of testosterone?
- Inducing male secondary sex characteristics
- Anabolic
What are the side effects of testoesterone?
- Acne
- Increases aggression
- Has adverse effects of lipid profiles, particularly the HDL-C/LDL-C ratio
What does the effect of testosterone on lipid profiles account for?
The increased risk of atherosclerotic disease in males and gender reassigned females
What are the sex steroid hormone inhibitors and antagonists?
Weak oestrogens that block receptors
What is clomiphene used for?
Ovulation induction
How does clomiphene induce ovulation?
It inhibits oestrogen binding to its ER in the anterior pituitary, and therefore inhibits negative feedback, resulting in increased FSH and LH expression
What is the use of tamoxifen?
It reduces the risk of breast cancer
How does tamoxifen reduce the risk of breast cancer?
Binds to ER in breast tissue and blocks oestrogen-stimulated myoepithelial cell division
What is mifepristone used for?
- Medical termination of pregnancy
- Induction of labour
What does mifepristone do?
- It is a partial agonists to the progesterone receptor, and inhibits progesterone action
- Sensitises uterus to prostaglandins
Give an example of an anti-androgen
Cyproterone
What is cyproterone a derivative of?
Progesterone
What effect does cyproterone have?
It has a weak progestogenic effect, as it is a partial agonist at the progesterone receptor, and so competes with dihydrotestosterone
Where is cyproterone used?
In the combined oral contraceptive pill
Give an example of a SERM?
Raloxifene
What effect does raloxifene have?
Oestrogen effects on bone, lipid metabolism, and blood coagulation
What are the advantages of raloxifene?
- Protects against osteoporosis
- No proliferative effects on endometrium and breast
- Reduced risk of invasive breast cancer in post-menopausal women with osteoporosis
What are the disadvantages of raloxifene?
Increases hot flushes and sweating
Give 5 drugs used in androgen replacement therapy
- Testosterone
- Enenthate
- Proprionate
- Undecanoate
- Mesterolone
How can androgen replacement therapies be administered?
- Implants
- IM
- Oral
What are the uses of androgen replacement therapy?
- Prevents hair loss, and so used in treatment of male pattern baldness
- Used in treatment of benign prostatic hypertrophy
Why is finasteride not approved for use in women?
Due to risks of birth defects in a fetus
