Sex Hormones: Male

Question 1

How do water soluble hormones work?

Answer 1

They travel freely in the blood
E.g. adrenaline

Question 2

How do liquid soluble hormones get transported and what is the main function of both?

Answer 2

They are bound to a transport protein called hormone binding proteins.
E.g. these hormones are sex hormones

Sex hormone binding globulin (SHBG) e.g. androgens and oestrogens, they will present them to the cell where they will be released and transported into them cell to do its function.

Corticosteroid binding globulin (CBG) e.g. corticosteroids and progesterone

Question 3

What would happen if we have altered levels of the SHBG and CBG proteins?

Answer 3

altered levels of these proteins may leads to hormone problems

Question 4

What is testosterone?

Answer 4

This is a primary male hormone

Question 5

Where is testosterone secreted from?

Answer 5

It is secreted from the testes in males but in small quantities is also secreted from the adrenal glands

Question 6

Where is testosterone metabolised?

Answer 6

It is metabolised by the liver or in target tissues with extensive first pass hepatic metabolism

Question 7

What is the actions of testosterone?

Answer 7

-Sexual differentiation in the foetus
-sexual development of the m,ale sex organs such as testis, penis, prostate at puberty and the maintenance of these tissues in adults.
-spermatogenesis in adults (this is the cell development of sperm cells)
-testosterone drives sperm production
-stimulation and maintenance of sexual function and behaviour
-anabolic agent increase in the bulk of tissues such as muscle and bone
-induces several liver enzymes
-stimulates the production of erythropoietin ( these are hormones produced by the kidneys to work in the production and maintenance of red blood cells) by the kidneys leading to higher haemoglobin concentrations in men than in women.

Question 8

______________ is the most potent form of testosterone. It has 2x affinity for the androgen receptor and5 times slower than the other.

Answer 8

Dihydrotestosterone

Question 9

Which ligands can bind to the androgen receptor?

Answer 9

Dihydrotestosterone and testosterone

Question 10

Where are the androgen receptors found?

Answer 10

They are found within male reproductive tissues

Question 11

What is the enzyme called that converts testosterone to Dihydrotestosterone?

Answer 11

5 alpha reductase
WE CAN USE THIS AS A THERPAY

Question 12

Where does testosterone bind?

Answer 12

It binds on the c terminus on the ligand binding domain, this will activate the receptors.

Question 13

When is androgen replacement therapy used?

Answer 13

-delayed puberty
-androgen insufficiency (testes no producing enough)
-castrstion ( testicle cancer)
-male andropause

Question 14

What androgen replacement therapy is given?

Answer 14

Mesterolone
Or
Testosterone

Question 15

When are anabolic steroids given?

Answer 15

These Are given if a patient experiences muscle wasting diseases

Question 16

What anabolic steroids are used?

Answer 16

Nandrolone
Or
Oxymetholone

Question 17

When is anti androgen therapy used and what is it used for?

Answer 17

This stops the effects of androgens they can be used in:
-hair loss
-prostate enlargement (begin)
-prostate cancer

Question 18

What anti androgen therapy is there available?

Answer 18

-finasteride
-bicalutamide
-zoladex

Question 19

What are the two major urinary metabolites in regards to sex hormones (males )?

Answer 19

Eticholanolone
Or
Androsterone

Question 20

How are androgens given?

Answer 20

They are typically given as a parenteral dosage form

Question 21

What happens when you add an alkyl group onto the p;option 17 on the androgen?

Answer 21

It slows down metabolism and effective lymph improves the oral activity. Thus more bioavailability

Question 22

What modifications can then allow the replacement therapy of androgen to be given orally?

Answer 22

This is the addition of an alkyl group at position 17

Question 23

What modification on the androgen can be made in order to be able to give androgen replacement therapy by the parenteral form?

Answer 23

We would add the addition of an ester on position 17

Question 24

What is the different between androgenic and anabolic?

Answer 24

Androgenic refers to : male sex characterises
-deepening of the voice
-hair and beard growth
-puberty
-maturation of sex organs

Anabolic refers to :building of tissue
-muscle
-bone
-increased red blood cell production for carrying oxygen

IN REALITY ALL AGENTS ARE BOTH ANABOLIC-ANDROGENIC STEROIDS

Question 25

What is the job of anabolic steroids?

Answer 25

They work by increasing protein synthesis
-they build up tissue and muscle and delayed puberty

Question 26

What is the dangers of anabolic steroids?

Answer 26

It can drive prostate diseases later on in life

Question 27

What side effects are there in regards to anabolic steroids?

Answer 27

-change of the vocal cords
-hair growth
-acne
-liver and heart failure

This means that they have androgenic effects as the first 3 are seen when androgens are present

Question 28

What is the correlation between DHT and hair loss and how could we stop it?

Answer 28

High levels of DHT drives the reduction of hair and contributes to hair loss

To stop the hair loss:
We could use blockage of androgens to slow down the hair loss.
E.g. finasteride

Question 29

What are the side effects of finasteride?

Answer 29

Loss of libido (loss of sexual function)
Erectile dysfunction
Breast tenderness
Depression
Anxiety

Question 30

Where is the prostate gland found?

Answer 30

THIS IS PART OF THE MALE REPRODUCTIVE SYSTEM
It is found surrounding the neck of the bladder and urethra and is enclosed in a fibrous capsule .

Question 31

What is benign prostate hyperplasia?

Answer 31

This is enlargement of the prostate gland, this is thickening of the tissue and patients often find it harder to feel completely emptied.

The gland continues to get bigger and bigger, squeezing the urethra and thus causing urinary issues

Question 32

How can we reverse being prostate hyperplasia?

Answer 32

If we can control the androgens we can reverse BPH

Question 33

How does finasteride work?

Answer 33

It works by blocking the conversion of testosterone to dihydrotestosterone. It is a competitive inhibitor from 5 alpha reductase.
-slows down the most potent DHT, so till get the testosterone effect

Question 34

How to treat prostate cancer and explain how the drug zoladex works?

Answer 34

Use androgen blockade known androgen deprivation therapy
Target both the production of testosterone and the receptor itself

Orchiectomy - this is removal of the testes

Or

Give LHRH agonists
These are drugs that lower the amount of tester one made by the testicles.it effects the feedback loop mechanism driving the pituitary gland it causes the negative feedback to overdrive, initially the patient will receive the production of a lot of testosterone but however this will shut down the pituitary gland and the hypothalamus, thus working in the brain . E.g. zoladex

Question 35

What is zoladex?

Answer 35

It is a synthethic analogue of LHRH

Question 36

How does bicalutamide work in the treatment t of prostate cancers ?

Answer 36

It works by directly preventing the binding of ligands, and stops the activation of androgen receptor. Bicalutamide sits in the same pocket as H12 and changes shape, thus meaning H12 is unable to bind to then activate the receptor. (Works as an antagonist)

-it is potent anti androgen effect
-leads to tumour shrinkage

Question 37

__________ is first line for treatment in prostate cancer

Answer 37

Bicalutamide

Question 38

What is the difference between finasteride and bicalumtide?

Answer 38

Finasteride stops the conversion from testosterone to DHT

Bicalumtide, prevents the binding of H12 into the pocket where it can go to activate, this drug sits in the same position as H12 would normally sits and acts as an antagonist to essentially block the integration of H12 to activate the receptor, thus no activation of the receptor and thus no androgens are activated