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
What is infant formula made out of?
- 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!)
What are the components of human milk that are not found in infant formula?
[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
What are some benefits of human milk?
[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
What is Colostrum?
- 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)
What is transitional milk and when is it produced?
within a few days after delivery
When is mature milk produced from the mammary glands?
after 1 to 2 weeks
What is weaning?
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)
