Male Reproductive Endocrinology

Question 1

How does the HPG axis work in males (Simple)?

Answer 1

Hypothalamus releases GnRH which tells pituitary to release LH and FSH

Question 2

What does optimal spermatogenesis require and where are these released from?

Answer 2

Testosterone is released from leydig cells after LH stimulates them

FSH is released from the pituitary

Question 3

Where is the LH receptors expressed?

Answer 3

Leydig cells

Question 4

What is the major product of the leydig cells?

Answer 4

Testosterone produced by the delta 5 pathway in humans of the delta 4 pathway in rodents

Question 5

How does leydig signalling stimulate leydig cell steroidogenesis?

Answer 5

The receptor signals and induced phosphorylation and activation of StAR which upregulates transcription of steroidogenic enzymes.

Question 6

What would happen if you inactivate LH or the LH receptors on key components (External genitalia at birth, puberty, testosterone, LH)?

Answer 6

External genitalia at birth = Male if LH is inactivated, female if LH receptors inactivated

Puberty - delayed in LH inactivation and absent in receptor inactivation.

Testosterone - low in LH inactivation and low in receptor inactivation

LH - absent in LH inactivation and high in receptor inactivation

Question 7

What is dependant on the LH receptor and what is dependant on LH itself?

Answer 7

Male sexual differentiation = receptor

Postnatal testicular development and spermatogenesis = LH

Question 8

Are testosterone levels higher in the testes than in the circulating blood?

Answer 8

Testes

Question 9

Why is testosterone converted to DHT in the blood and what does this?

Answer 9

Testosterone is concentrated enough in the testes to work but not in the blood and so its changed to the highly concentrated DHT.

5 alpha-reductase does this

Question 10

How do androgens work?

Answer 10

Testosterone and DHT bind to AR’s better than the other androgens which is why they are the only active androgens. The other androgens can be used as intermediates.

These receptors can act as both a receptor and a transcription factor

Question 11

What are the 3 surges of testosterone and what do they do?

Answer 11

Embryonic stage - helps the fetus develop male reproductive tract

Neonatal stage - no one knows

Continous post-puberty - spermatogenesis, male secondary sexual characteristics.

Question 12

What happens in humans with inactive AR?

Answer 12

Complete androgen insensitivity syndrome (CAIS)

These individuals are assigned female at birth but have no ovaries, uterus and a short vagina. They have abdominal testes.

They do not know they are XY until puberty as they do not menstruate and will be told by the doctors.

Most chose to get testes removed and stay female.

Question 13

What are ARKO mice?

Answer 13

Androgen receptor knockout mice which are a model for cais which show undescended testes, absent spermatogonia and no wolffian duct-derived structures developed.

Question 14

How do you make conditional AR knockout mice?

Answer 14

Cre/loP transgenic system to make knockout of gene of interest in one cell type

Question 15

What would happen in a sertoli-specific androgen receptor knockout (SCARKO)?

Answer 15

Normal testes descent and repro organs. Infertile due to a block of spermatogenesis at meiosis and blood testes disruption

Question 16

What would happen in a PTM cell-specific androgen knockout mouse (PTM-ARKO)?

Answer 16

Normal testis descent and normal repro organs. Infertile with reduce sperm at all spermatogenesis stages (but no block). Androgens work on PTM to stimulate GDNF

Question 17

What would happen in a leydig cell androgen receptor knockout (LCARKO)?

Answer 17

Normal testes and repro organs not infertile however the leydig cells dont develop properly and apoptose in adulthood.

Question 18

What are the different types of DHT and where are they found?

Answer 18

Type 1 DHT - organs not associated with reproduction e.g chest and back skin

Type 2 DHT - organs more associated with reproduction e.g testes and helps grow beard

Both share liver

Question 19

What is 5 alpha reductase type 2 deficiency?

Answer 19

When someone has an XY genotype with a mutation in the Srd5a2 gene they appear female at birth as their male repro organs are inside the body until puberty hits. The when it does their phenotype changes and they become male. They however have short penises and therefore cant reproduce naturally but everything else works fine and they can do IVF etc.

Question 20

Where is the FSH receptor expressed?

Answer 20

Sertoli cells

Question 21

What does FSH do to sertoli cells?

Answer 21

FSH released during fetal and neonatal development stimulating mitosis. Also stimulates them signalling to support developing germ cerlls, production of androgen binding protein and stimulate inhibin production.

Question 22

What happens to testes size, sertoli, spermatogonia, mature spermatozoa and fertility when inactivating FSH receptor and FSH?

Answer 22

Testes size = smaller when both FSH and its receptor inhibited

Sertoli - are fewer when both FSH and receptor are inactive

Mature spermatozoa are none when FSH inactive and few when receptor is inactive.

Fertility - infertile when no FSH, variable when the FSH receptor is inactive

Question 23

What two hormones are part of the gonadal feedback of the hypothalamus and what do they do?

Answer 23

Testosterone inhibits pituitary and hypothalamus

Inhibin B inhibits pituitary secretion of FSH

Question 24

Where is steroid negative feedback in the hypothalamus at?

Answer 24

The Kisspeptin neurons

Question 25

Where is inhibin produced and what does it do?

Answer 25

Inhibibin A produced by sertoli cells in response to FSH and inhibin Betab is produced mainly by maturing sperm cells

Question 26

How does inhibin B repress FSH release?

Answer 26

Acts on pituitary gonadotrophin repressing their gene expression including Fshb.

Question 27

How do testosterone injection male contraceptives work?

Answer 27

Injecting slow release testosterone results in the hyp/pit supression of endogenous LH production (this happens as ny testosterone in the blood and not the testes it directly inhibits). This causes testes shrinkage