3. Anterior Pituitary and its hormones

Question 1

What is the anatomical connection between the hypothalamus and the anterior pituitary gland?

Answer 1

Hypothalamo-hypophyseal-portal system

• A system of tiny capillaries that moves hormones quickly from the hypothalamus to the anterior pituitary.

Question 2

Name 6 hormones that the anterior pituitary produces.

Answer 2

1. TSH
2. ACTH
3. GH
4. Prolactin
5. FSH
6. LH

Question 3

Mechanism:
Synthesis of ACTH in the anterior pituitary (AP)

Answer 3

In corticotroph cells
↓
Pre-proopiomelanocortin (pre-POMC)
↓
Cleavage of its signal peptide
↓
Proopiomelanocortin (POMC)
↓
Split into multiple peptide hormones e.g. ACTH
↓
ACTH stored in granules in the corticotroph cells

Question 4

Mechanism:
Release of ACTH - hypothalamus to anterior pituitary (AP) axis

Answer 4

Hypothalamus -> CRH -> Hypophyseal-portal system -> corticotroph cell in AP -> ACTH

Question 5

What is the pattern of ACTH release?

Answer 5

Pulsatile
- Peaks in the morning around 6 AM

But: also in various form of stressful stimuli e.g. hypoglycaemia, infection and increased pro-inflammatory cytokines

Question 6

Mechanism:
ACTH binding to target cells in the adrenal glands

Answer 6

ACTH -> binds to ACTH receptor (Melanocortin receptor 2) on adrenocortical cells in the zona fasciculata in the adrenal cortex

Also:
ACTH -> binds to ACTH receptor (Melanocortin receptor 1) on melanocytes in the skin -> activated -> causes melanocytes to switch from yellow/red pheomelanin to brown/black eumelanin

Question 7

Mechanism:
Release of TSH from the anterior pituitary

Answer 7

Hypothalamus -> TRH -> Hypophyseal-portal system -> Thyrotropic cells in AP -> TSH

Question 8

Mechanism:
TSH binding to target cells in the thyroid gland

Answer 8

TSH -> binds to thyroid receptor on follicular cells in the thyroid

Question 9

Mechanism:
Release of GH - hypothalamus to anterior pituitary (AP) axis

Answer 9

Hypothalamus -> GHRH/Somatotropin -> Hypophyseal-portal system -> Somatotroph cells in AP -> GH

Question 10

Mechanism:
GH binding to target cells

Answer 10

GH -> must bind to 2 GH receptors to activate intracellular signalling -> dimerisation of 2 GHRs

GH -> 2x GHR -> Liver/Bone/Muscles/Adipose tissue -> Somatomedin e.g. insulin-like growth factor 1 (IGF-1)

Question 11

What is the function of IGF-1?

Answer 11

It induces cell division, cartilage and skeletal growth and protein synthesis.

Question 12

What is the pattern of GH release?

Answer 12

Secreted in a pulsatile fashion every ~2 hrs
Peaks 1 hr after falling asleep
Increases during deep sleep (sleep stages III + IV)

Question 13

What increases GHRH release from the hypothalamus?

Answer 13

1. Hypoglycaemia
2. Puberty
   - ↑↑ Oestrogen/testosterone -> GHRH release
3. Stress (fevers/trauma)
4. Exercise
   - Adrenal glands secrete adrenaline -> GHRH release

Question 14

Mechanism:
Inhibition of GH - hypothalamus to anterior pituitary (AP) axis

Answer 14

Hypothalamus -> GHIH/Somatostatin -> Hypophyseal-portal system -> Somatotroph cells in AP -> blocks GHRH from acting on the somatotrophs -> Inhibits GH secretion from AP

Question 15

GH has direct and indirect effects. State 3 main direct effects of GH.

Answer 15

1. For Carbohydrates: ↑↑ blood glucose
   - Stimulates gluconeogenesis + glycogenolysis in the liver
2. For Fats: ↑↑ fatty acids in the blood
   - Stimulates adipose tissue lipolysis
3. Anti-insulin-like effects
   - ↑↑ insulin resistance in tissues

Question 16

GH has direct and indirect effects. State 3 main indirect effects of GH.

Answer 16

1. Steady release of IGF-1 in bones, liver, kidneys
   - ↑↑ cellular metabolism
   - ↑↑ cell division/differentiation rate
   - Prevents cell death
2. Stimulates amino acid uptake into muscle cells
   - Protein production & muscle growth
3. Growth of long bones
   - Acts on epiphyseal cartilage (growth plates)
   - Stimulates osteoblast + chondrocyte activity
   - Boosts growth (growth spurts + puberty)

Question 17

Mechanism:
Release of Prolactin - hypothalamus to anterior pituitary (AP) axis

Answer 17

Hypothalamus -> TRH (Prolactin releasing hormone) -> Hypophyseal-portal system -> Lactotroph cells in the AP -> Prolactin

Question 18

Mechanism:
Inhibition of Prolactin - hypothalamus to anterior pituitary (AP) axis

Answer 18

Hypothalamus -> Dopamine (Prolactin inhibiting factor) -> Hypophyseal-portal system -> Binds to specific receptors on Lactotroph cells in the AP -> Inhibits Prolactin release from AP

Question 19

State 3 functions of Prolactin

Answer 19

1. Preparation for lactation during pregnancy
   - Breast growth
2. Milk production (lactogenesis) during breastfeeding
   - Stimulates milk-secreting epithelial cells
3. Inhibits GnRH release
   - Inhibits FSH + LH release -decreases oestrogen levels - no follicular development - typically no ovulation or menstruation during breastfeeding
   - In men: decreases testosterone production

Question 20

What is the difference in the effect of Prolactin during pregnancy and after birth?

Answer 20

During pregnancy:
- Oestrogen + Progesterone: inhibit milk production until birth

After birth:
- Detachment of placenta from uterine walls -> Low oestrogen/progestrone levels - Prolactin release
- Can stimulate milk-producing epithelial cells
- Further increased by breastfeeding

Question 21

What would happen to serum prolactin levels if something was to impact on the pituitary stalk and block dopamine release?

Answer 21

Prolactin levels would increase.