Lecture 1 - Steroids, the receptors, and the testis

Question 1

The three sex steroid families

Answer 1

Estrogens
Progestins
Androgens

Question 2

Do men produce estradiol?

Answer 2

In men, estradiol is produced by the testis at roughly 20% of the level in non-pregnant women

Question 3

How do hormones move through the body?

Answer 3

They are hydrophobic compounds that circulate in the blood - bound to carrier proteins and can pass through cell membranes

Question 4

Sex steroid synthesis: where does it arise from?

Answer 4

All sex steroid are derived from cholesterol (which is formed from acetate)

Question 5

Do women require astrogens?

Answer 5

Yes, Androgens are obligatory precursors of estrogens in both
male and female

Question 6

If all cells contain the DNA of the organism, why don’t all cells react to sex hormones?

Answer 6

Different cells have different phenotypes due to the parts of the genome that are expressed

Only cells with an estrogen, progestin, or androgen receptor (ER/PR/AR) will respond to the sex hormones circulating

Question 7

ER, PR, and AR: what are they?

Answer 7

• Estrogen receptor
• Progestin receptor
• Androgen receptor

These receptors are transcription factors - once activated they will cause certain genes to be transcribed

Question 8

Androgens, progestins, and estrogens: what are they described as?

Answer 8

They are defined as compounds that interact with (bind directly to) the A/P/ER, causing a downstream biological response

Question 9

Steroid receptors: what is their structure and how do they do their action?

Answer 9

Dimers that bind to steroid hormones and undergo a conformational change

Moves to nucleus and binds with its DNA binding domain and allows other molecules to bind (ie RNA polymerase) and causes genes to be transcribed

Question 10

Does estrogen only affect the ER?

Answer 10

No, estrogen action also leads to expression of progesterone receptor and downstream activation of a new set of genes

Question 11

Testicular anatomy: where is sperm produced?

Answer 11

Seminiferous tubules

Question 12

Sertoli cells: what are they and what do they do?

Answer 12

Nurse cells

Help in supporting, protecting, and providing nutrition to spermatogenic cells

Question 13

What structures are between seminiferous cells?

Answer 13

Leydig cells

Question 14

Leydig cells: what do they do, what is significant about their function, and what is important about their signalling?

Answer 14

Synthesis and secretion of testosterone

The whole pathway from cholesterol to androgen happens in Leydig cells

Testosterone acts back on the AR in the Leydig cell to promote survival - autocrine effect

Question 15

Myoid cells: what are they and what do they do?

Answer 15

Contractile cells surrounding seminiferous tubules

Involved in the transport of spermatozoa and testicular fluid through the tubule

Question 16

DHT: what is it, where is it made, what is its production catalysed by, and what does it do?

Answer 16

DHT is dihydrotestosterone,
a more potent androgen than
testosterone itself

Made in sertoli cells

Catalysed by 5-alpha reductase

In adults, DHT is needed for sperm motility.

It has a critical role in male sexual development – a shortage of this hormone disrupts the formation of
the external sex organs before birth

Question 17

Androgen receptors: how does their knockout affect male and female mice?

Answer 17

• The AR-null (ARKO) male mouse develops with very small testes (20% normal)
• Spermatogenesis is arrested before full maturation
• The animals show some resemblance to the female
• The ARKO female has reduced litter sizes - androgens are important in the female too

Question 18

Aromatase: how does its knockout affect mice development?

Answer 18

The mice lack estrogen

In males, spermatogenesis begins but fails

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