Hypothalamic - Pituitary Gonadal Axis I

Question 1

What are the 7 things needed to reproduce?

Answer 1

→Correct process of sex determination (genotypic sex) and differentiation (phenotypic sex)
→Sexual maturation- Puberty
→Production and storage of sufficient supply of gametes
→Correct number of chromosomes in egg and sperm
→Actual sexual intercourse
→Fertilisation, implantation, embryonic and placental development
→ nurture individual until capable of “independent” life

Question 2

What is an example of positive feedback?

Answer 2

→ Ovulation

Question 3

Describe how the HPG axis works?

Answer 3

→+ve drive from the hypothalamus which activates the pituitary
→ +ve drive causing hormonal release from the pituitary
→ Causes release of steroid hormones from the gonads
→ Work in a -ve feedback to regulate their production

Question 4

What does type of hormones does the hypothalamus produce?

Answer 4

→ Peptide hormones

Question 5

What hormones does the hypothalamus produce?

Answer 5

→Gonadotropin releasing hormone

→kisspeptin

Question 6

What hormones does the pituitary produce?

Answer 6

→ Follicle stimulating hormone

→ LH

Question 7

What hormones do the gonads produce?

Answer 7

→ Estradiol
→ Progesterone
→ Testosterone
→ Inhibin
→ Activin

Question 8

Describe the HPG axis in relation to FSH and LH?

Answer 8

→ GnRH is released from the hypothalamus
→ This binds to the receptor on the anterior pituitary
→ LH and FSH are secreted
→ FSH and LH are released into the circulation and bind to their receptors on the gonads
→ this co-ordinates the secretion of estrogen, progesterone and androgens

Question 9

Where is GnRH secreted into?

Answer 9

→ Into the primary plexus of the median eminence

Question 10

Where does GnRH travel after it is secreted?

Answer 10

→ Into the hypophyseal portal into the anterior pituitary

Question 11

What does GnRH act on?

Answer 11

→ The gonadotroph cells in the anterior pituitary

Question 12

What is the function of kisspeptin?

Answer 12

→ Master controller of puberty

Question 13

Where is kisspeptin expressed?

Answer 13

→ In the arcuate nucleus

→ AVPV nucleus

Question 14

What do kisspeptin neurons do?

Answer 14

→ They send signals upstream of GnRH to neurons

Question 15

What receptor do the kisspeptin neurons bind to?

Answer 15

→ GPR54 receptor on GnRH neurons

Question 16

What can kisspeptin 54 cross?

Answer 16

→ blood brain barrier

Question 17

What type of hormone is kisspeptin?

Answer 17

→ Peptide hormone that is cleaved from a large pre-pro structure

Question 18

What is GnRH secreted in response to and where?

Answer 18

→ Synthesized and secreted in response to kisspeptin

→ From GnRH neurons

Question 19

What type of release is GnRH?

Answer 19

→ Pusatile

Question 20

Where does GnRH bind?

Answer 20

→ To the GnRH receptor on gonadotroph cells of the anterior pituitary

Question 21

Where does GnRH travel from and to?

Answer 21

→ from the arcuate nucleus to the median eminence to the anterior pituitary

Question 22

What is GnRH produced from?

Answer 22

→ a Prepro protein

Question 23

What is GnRH spliced into?

Answer 23

→ Decapeptide

Question 24

What is GnRh co-secreted with?

Answer 24

→ GAP

→ GnRH

Question 25

When is GnRh secreted?

Answer 25

→ every 30-120 minutes

Question 26

What does GnRH stimulate?

Answer 26

→ A pulse of LH and FSH secretion from the pituitary

Question 27

What types of GnRH pulse favor LH and what types favor FSH?

Answer 27

→ slow frequency - FSH | → rapid frequency - LH

Question 28

What does continuous release of GnRH lead to?

Answer 28

→ Cessation of response

Question 29

What hormone gets produced after a surge in LH and estradiol and what happens to the follicle?

Answer 29

→ Progesterone | → Remodelling of the ovarian follicle into the corpus luteum

Question 30

How does native GnRh binding work?

Answer 30

→ GnRH binds to its receptor → It activates a signaling pathway cascade → Stimulates gonadotrophin synthesis and secretion → GnRH dissociates from its receptor → Receptor is ready to respond to the next GnRH pulse

Question 31

How does a GnRH agonist work?

Answer 31

``` → Binds to the receptor → Activates signaling → Stimulates gonadotrophin synthesis and secretion at first → Doesn't dissociate → GnRH is uncoupled → Receptor is unresponsive ```

Question 32

How does a GnRH antagonist work?

Answer 32

→ Binds to the receptor → Blocks the receptor → No downstream effect and LH and FSH are switched off

Question 33

What are 6 uses of GnRH analogues?

Answer 33

``` → IVF → Prostate cancer → Breast , ovarian and endometrial cancer → Endometriosis → PCOS → Fibroids ```

Question 34

How does GnRH cause FSH and LH to increase?

Answer 34

→ Increases the transcription and translation of the subunits that make up LH and FSH

Question 35

What are the gonadotrophin hormones?

Answer 35

→ LH → FSH →hCG

Question 36

What type of peptides are the gonadotrophin hormones?

Answer 36

→ Heterodimeric peptides → Common a subunit → Hormone specific B subunit

Question 37

What is required for biological function of heterodimeric peptides?

Answer 37

→ N linked carbohydrate side chains

Question 38

What happens if N linked carbohydrate chains are deglycosylated?

Answer 38

→ They still bind but they are inhibitory

Question 39

Which subunit of the gonadotrophic hormones are made in excess?

Answer 39

→A subunits are synthesized in excess

Question 40

What is the function of LH in the testes?

Answer 40

→ Stimulation of Leydig cells and androgen synthesis

Question 41

What is the function of LH in the ovary?

Answer 41

→ Stimulation of Theca cells and androgen synthesis → Ovulation → Progesterone production of corpus luteum

Question 42

What is the function of FSH in the testis?

Answer 42

→ Regulation of Sertoli cell metabolism

Question 43

What is the function of FSH in the ovary?

Answer 43

→ Follicular maturation | → Granulosa cell - estrogen synthesis

Question 44

Where are the Leydig cells between?

Answer 44

→ Seminiferous tubules

Question 45

What do Leydig cells express?

Answer 45

→ LH receptor

Question 46

What is lining the seminiferous tubules and what is their function?

Answer 46

→ Sertoli cells which express the FSH receptor | → Co-ordinate spermatogenesis

Question 47

What are the cells that line the ovarian follicle called?

Answer 47

→ Theca cells

Question 48

What do Theca cells do?

Answer 48

→ Stimulate androgen production

Question 49

What do granulosa cells express?

Answer 49

→ FSH receptors

Question 50

How are androgens converted to estrogens?

Answer 50

→ Androgens cross the basement membrane and go to the granulosa cells → They are converted via the aromatase enzyme.

Question 51

What regulates aromatase?

Answer 51

→ FSH receptors

Question 52

What is produced in the corpus luteum?

Answer 52

→ Progesterone

Question 53

Describe the HPG axis in females?

Answer 53

→ Kisspeptin and GnRH are released from the hypothalamus → GnRH travels to the gonadotroph cells of the anterior pituitary → It causes the synthesis and secretion of LH and FSH → LH binds to its receptor on Theca cells → Stimulates androgen production → FSH binds to its receptor on Granulosa cells → This causes the conversion of androgens to estrogens → Within the luteal phase you get progesterone produced → These feedback negatively except estradiol

Question 54

Describe the HPG axis in males?

Answer 54

→ From the hypothalamus kisspeptin and GnRH are released → GnRH travels to the gonadotroph cells of the anterior pituitary → it causes the synthesis and secretion of LH and FSH → LH binds to its receptor on Leydig cells to produce testosterone → FSH binds to its receptor on Sertoli cells to maintain spermatogenesis → They all feedback negatively