REB 17. Biochemistry of the Mammary Gland + Lactation Flashcards
Breasts develops/differntiate during pregnancy through several hormones which are…? What is the most critical hormone?
- Prolactin (most critical)
- progesterone
- estrogens
- growth hormone
- cortisol
- human placental lactogen (hPL)
What type of gland is the mammary gland?
Exocrine gland - secretes into ducts
What are the 2 main functions of the mammary gland?
[1] Food (fat, protein, sugar, vitamins, minerals, water…)
[2] Protection (immunity)
What are the 2 layers of cells in the breast lobule?
[1] Myoepithelial Cells
- contract in response to oxytocin to secrete milk into the lumen
[2] Luminal Epithalial Cells
- they produce milk during lactation
How long should a mother feed the baby exclusively just by breast feeding?
6 months
- breast milk provides all the nutrients the baby requires
Continue to breast feed in combination with complementary food for 2 years
What are the cells in the anterior pituitary that produce prolactin?
Lactotrophs
What is the base line signal for lactation? Inhibitory or excitatory?
- inhibitory signal
- dopamine inhibits lactation
- dopamine acts on D2 receptor of lactotrophs in the anterior pituitary
What hormone leads to the excitatory aciton on lactation?
Thyrotropin-Releasing Hormone (TRH)
Which 2 stimuli + hormone feeds back into a positive feedback loop into the hypothalamus leading to more milk production (lactation)?
[1] Suckling Reflex (baby breast feeding)
[2] Prolactin
Describe the levels of prolactin secreted throughout pregnancy, at night time and postpartum.
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
What inhibitory effects does prolactin enact?
[1] it suppresses the gonadotropins (FSH + LH)
[2] inhibits the response of the ovaries to hormones (ovulation does not occur)
What is hyperprolactinaemia?
it is an overproduction of prolactin
What are some causes of hyperprolactinaemia?
[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
What can hyperprolactinaemia cause?
[1] Infertility
[2] Galactorrhea (inappropriate lactation)
What are the 3 phases that the maternal breast undergoes during and after pregnancy?
[1] Mammogenesis
- development of ducts + alveolar systems
[2] Lactogenesis
- milk synthesis
[3] Galactogenesis
- milk letdown (release)
What happens in mammogenesis? What are the crucial hormones involved in this phase?
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)
What happens in lactogenesis? What are the 3 phases of this major phase? Explain the timings and the hormones prevalent and what happens.
[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)
What type of sugar is lactose?
disaccharide
What monosaccharides is lactose made up of?
[1] glucose
[2] galactose
How do you synthesize lactose?
2 glucoses required
- 1 glucose +
- 1 glucose –> UDP-glucose –> UDP-galactose
= lactose
The lactase synthase enzyme is made up of 2 parts which are:
[1] Catalytic Component
- galactosyltransferase (GT)
[2] Regulatory Component
- alpha-lactalbumin (alpha-LA)
In the galactogenesis phase, what is milk letdown activated by?
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
What are the major macronutrients in human milk?
[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
What are the main differences between human milk and bovine milk?
Human Milk:
- increased carbs than cows
- increased whey proteins than cows
- decreased casein than cows
- decreased minerals than cows
+ human milk has more lactose
