REB 17. Biochemistry of the Mammary Gland + Lactation

Question 1

Breasts develops/differntiate during pregnancy through several hormones which are…? What is the most critical hormone?

Answer 1

• Prolactin (most critical)
• progesterone
• estrogens
• growth hormone
• cortisol
• human placental lactogen (hPL)

Question 2

What type of gland is the mammary gland?

Answer 2

Exocrine gland - secretes into ducts

Question 3

What are the 2 main functions of the mammary gland?

Answer 3

[1] Food (fat, protein, sugar, vitamins, minerals, water…)

[2] Protection (immunity)

Question 4

What are the 2 layers of cells in the breast lobule?

Answer 4

[1] Myoepithelial Cells
- contract in response to oxytocin to secrete milk into the lumen

[2] Luminal Epithalial Cells
- they produce milk during lactation

Question 5

How long should a mother feed the baby exclusively just by breast feeding?

Answer 5

6 months
- breast milk provides all the nutrients the baby requires

Continue to breast feed in combination with complementary food for 2 years

Question 6

What are the cells in the anterior pituitary that produce prolactin?

Answer 6

Lactotrophs

Question 7

What is the base line signal for lactation? Inhibitory or excitatory?

Answer 7

• inhibitory signal
• dopamine inhibits lactation
• dopamine acts on D2 receptor of lactotrophs in the anterior pituitary

Question 8

What hormone leads to the excitatory aciton on lactation?

Answer 8

Thyrotropin-Releasing Hormone (TRH)

Question 9

Which 2 stimuli + hormone feeds back into a positive feedback loop into the hypothalamus leading to more milk production (lactation)?

Answer 9

[1] Suckling Reflex (baby breast feeding)

[2] Prolactin

Question 10

Describe the levels of prolactin secreted throughout pregnancy, at night time and postpartum.

Answer 10

THROUGHOUT PREGNANCY:
- gradually increases

NIGHT TIME:

• pre pregnancy around 5 to 20 ng/mL
• at term up to 200 ng/mL

POSTPARTUM:

• baseline levels remain elevated for 2 to 3 months
• prolactin surges with suckling/breast emptying

Question 11

What inhibitory effects does prolactin enact?

Answer 11

[1] it suppresses the gonadotropins (FSH + LH)

[2] inhibits the response of the ovaries to hormones (ovulation does not occur)

Question 12

What is hyperprolactinaemia?

Answer 12

it is an overproduction of prolactin

Question 13

What are some causes of hyperprolactinaemia?

Answer 13

[1] pituitary adenomas

[2] reduced dopamine levels (leads to disinhibition)
- e.g. compression of pituitary stalk by mass lesions blocks the flow of dopamine from brain to prolactin-secreting cells

[3] physiological stimuli - suckling

[4] hormonal effects

• pregnancy
• estrogen therapy
• hypothyroidism (this leads to increase in TRH)

[5] drugs

• antipsychotic drugs (are dopamine antagonists)
• opiates

Question 14

What can hyperprolactinaemia cause?

Answer 14

[1] Infertility

[2] Galactorrhea (inappropriate lactation)

Question 15

What are the 3 phases that the maternal breast undergoes during and after pregnancy?

Answer 15

[1] Mammogenesis
- development of ducts + alveolar systems

[2] Lactogenesis
- milk synthesis

[3] Galactogenesis
- milk letdown (release)

Question 16

What happens in mammogenesis? What are the crucial hormones involved in this phase?

Answer 16

Mammogenesis: steroid hormones act with maternal prolactin to DEVELOP DUCTS and ALVEOLAR SYSTEMS

Required:
[1] Prolactin (completes cellular differentiation and development of lactogenic capacity)

[2] Estrogen (stimulates DUCTAL development; development begins at puberty)

[3] Progesterone (develops ALVEOLAR SYSTEM)

[4] Insulin (required for multiplication of epithelial cells + development of lobulalveolar architecture)

Question 17

What happens in lactogenesis? What are the 3 phases of this major phase? Explain the timings and the hormones prevalent and what happens.

Answer 17

[1] Lactogenesis I (mid pregnancy - 30 hours after birth)

• INCREASE IN PROGESTERONE
• lactogenic capability present, but high levels of progesterone inhibits milk secretion + supresses volume

[2] Lactogenesis II (30 to 40 hours after birth)

• DECREASE IN PROGESTERONE, INCREASE IN PROLACTIN
• delivery of placenta (decreased progesterone)
• high prolactin (and sudden decline of progesterone) causes increase in milk volume

[3] Lactogenesis III (2/3 months post partum onwards)

• established lactation
• autocrine/local control of milk synthesis
• primary control mechanism is baby suckling (baby’s appetite)

Question 18

What type of sugar is lactose?

Answer 18

disaccharide

Question 19

What monosaccharides is lactose made up of?

Answer 19

[1] glucose

[2] galactose

Question 20

How do you synthesize lactose?

Answer 20

2 glucoses required
- 1 glucose +
- 1 glucose –> UDP-glucose –> UDP-galactose
= lactose

Question 21

The lactase synthase enzyme is made up of 2 parts which are:

Answer 21

[1] Catalytic Component
- galactosyltransferase (GT)

[2] Regulatory Component
- alpha-lactalbumin (alpha-LA)

Question 22

In the galactogenesis phase, what is milk letdown activated by?

Answer 22

Neurosensory Reflex

• the afferent stimuli from suckling reaches the posterior pituitary causing oxytocin release
• oxytocin causes contraction of myoepithelial cells
• leads to release of milk into lumen

Question 23

What are the major macronutrients in human milk?

Answer 23

[1] Carbohydrate

• lactose
• oligosaccharides

[2] Milk Fat (mainly in form of triglyceride)

[3] Proteins

• casein
• whey proteins (e.g. lactoferrin, secretory immunoglobulin A, alpha-lactalbumin)

[4] Minerals (e.g. sodium, potassium, chloride, calcium, magnesium…)

[5] Other Components

• enzymes (e.g. lipase to break down fat)
• vitamins
• trace elements
• growth factors

Question 24

What are the main differences between human milk and bovine milk?

Answer 24

Human Milk:

• increased carbs than cows
• increased whey proteins than cows
• decreased casein than cows
• decreased minerals than cows

+ human milk has more lactose

Question 25

What is infant formula made out of?

Answer 25

• made from cow’s milk

processing:

• alter whey-to-casein protein balance (increase whey, decrease casein)
• addition of several essential ingredients
• partial or total replacement of dairy fat with fats of vegetable or marine origin (to increase shelf life!)

Question 26

What are the components of human milk that are not found in infant formula?

Answer 26

[1] lactoferrin protein
[2] anti-infectious oligosaccharides + glycoconjugates
[3] growth factors
[4] long chain polyunsaturated fatty acids (LCPUFA)
[5] lipase enzyme (to digest fat)

+ breast milk automatically adjusts to infant’s needs

Question 27

What are some benefits of human milk?

Answer 27

[1] improved gastrointestinal function
[2] improved cognitive + visual development
[3] improved host defence
[4] enhanced maternal physiological well-being + maternal-infant bonding
- improves birth spacing
[5] ongoing research
- microbiome
- epigenetics
- stem cells

Question 28

What is Colostrum?

Answer 28

• first milk/liquid produced after birth by mammary glands
• it is yellow and thicker
• very high in concentrated nutrition (low in fat, high in proteins + carbs and very easy to digest)
• high concentration of antibodies
• laxative effect (helps baby pass first bowel)

Question 29

What is transitional milk and when is it produced?

Answer 29

within a few days after delivery

Question 30

When is mature milk produced from the mammary glands?

Answer 30

after 1 to 2 weeks

Question 31

What is weaning?

Answer 31

Weaning: reduction of breast milk and/or formula to replace it with more solid food

• after 6 months
• breastfeed + food until 2 years
• breast/formula milk should be used until 12 months, can then transition to cow milk (full fat important for baby development)