1.4 Hypothalamic-Pituitary-Gonadal (HPG) Axis

Question 1

What are the roles of the gonadotropins (FSH/LH) in males vs females?

Answer 1

Males — FSH promotes sperm production, LH promotes testosterone production

Females — FSH promotes follicle growth + oestrogen release from follicles, LH sustains corpus luteum, and spikes right before ovulation

Question 2

Describe the biochemical structure of GnRH (type of hormone, acid durability, size, BBB permeability,

Answer 2

• Peptide hormone (10 AAs; small)
• Not acid resistant (can’t come through stomach)
• Can cross blood brain barrier due to size

Question 3

What is the basis for the naturally pulsatile pattern of GnRH secretion? What are some therapeutic reasons why we might artificially violate this pattern?

Answer 3

• If GnRH is secreted continuously, GnRH receptors are desensitised, and so LH is not released. This leads to a state of castration
• In prostate/breast cancer, we induce this on purpose to decrease cancer growth

Question 4

Glycoprotein hormones are made of __ distinct chains, and the ____ chain is the unique one that gives the molecule its properties

Answer 4

• They are made of two chains (alpha and beta)
• The beta chain is the one that gives the unique properties

Question 5

Describe the biochemical structure of gonadotrophins (compare to GnRH)

Answer 5

• Peptide hormones (like GnRH)
• Larger protein than GnRH
• Because they’re peptides, like GnRH, they’re not durable in acid, and so cannot be given orally

Question 6

Draw the male gonadotrophin feedback loops

Answer 6

• GnRH increase gonadotrophs (FSH/LH)
• LH acts on Leydig cells, producing testosterone (decreases two above it)
• FSH acts on Sertoli cells -> prompts inhibin release, which inhibits LH/FSH release

Question 7

Describe female gonadotroph feedback loops during the luteal phase

Answer 7

• LH prompts the corpus luteum to release oestrogen and progesterone, which negatively feed back on the pituitary and the hypothalamus

Question 8

Describe female gonadotroph feedback loops during the follicular phase

Answer 8

• FSH acts on granulosa cells, which in turn produce inhibin
• LH acts on theca interna cells, resulting in production of oestrogen, which negatively feeds back on pituitary and hypothalamus (JUST PRIOR TO OVULATION, OESTROGEN BECOMES POSITIVE FEEDBACK ON GONADOTROPHINS; WE DON’T KNOW WHY)