Breast Development and Physiology Flashcards
3 aspects of breast development
1) Attraction - estrogen - sexual maturation, male/female differentiation
2)Reproduction - progesterone- functional differentiation
3)Nutrition - prolactin
(milk synthesis/secretion)
Why interest in breast development/physiology
- diseases in breast development/function important medical problems (cancer, hypomastic, macromastia, mastitis, galactorrhea)
- benefits to infant nutrition, health, development (nutritional advantage, reduced infectious diseases/mortality rate/lower SIDS rate, improved cognitive function)
Maternal benefits of breastfeeding
- decreased postpartum bleeding/more rapid uterine involution (oxytocin)
- decreased menstrual blood loss/increased child spacing (lactational amenorrhea)
- earlier return to pre-pregnancy weight
Stages of breast development and key hormones
- Increased estrogen in puberty + GH induce elongation and branching of ductal network by increasing IGF-1 production by stromal cells. Progesterone secretion in luteal phase brings about side branching and lobulo-alevolar development
- Why keeps duct from overgrowing – when reach maturity, GH goes down. Even with estrogen, no GH inhibits ductal elaboration.
- Progesterone needed for branching. TDLU regress at end of luteal phase unless pregnancy occurs. Can be functional (see casein production)
- After puberty, breast consists of mainly ducts with some alveoli–functional to some degree
What physiological factors affect lactation
These inhibit oxytocin production
- Anxiety/stress
- Delayed lactation initiation
- pituitary disorders or damage
- excessive weight (affects initiation and duration): problems with other metabolic adaptations shown in mice
-Normally about 20% of energy requirements are increased for humans during breastfeeding.
Women who no longer breastfeeding and hear baby cry, can get milk letdown. Stimulus produces oxytocin.
Organization of human breast
Lobes = glandular units of breast composed of multiple lobules containing alveoli (milk producing units) that are connected by a ductal network that empties into a single milk duct
- milk ducts from multiple lobes feed into nipple
Lobuloalveolar Unit
aka Terminal ductal lobular unit (TDLU)
- comprised of glandular (alveolar/secretory) epithelial cells and myoepithelial cells that contract to help move milk along. Have interlobular stroma and intralobular stroma.
- organization of glandular network makes it susceptible to damage during breast surgery
What is different in breast composition between lactating and non-lactating breast
In lactating breast, there is way more glandular tissue and a lot less intragland fat. Breast becomes filled with more lobular units during lactation. Ability to produce milk has more to do with ability of glands to develop, not necessarily amount of fat in breast.
Both composed of glandular tissue, intragland fat, subcutaneous fat, retromammary fat. Breast is very dynamic!
Breast development stages
- Embryogenesis: establish rudimentary gland. Mammary gland from ectodermal origin, invaginates into mesenchyme to create primary then secondary bud. Final neonatal mammary gland has ducts invading a fat pad. Need to have mesenchymal condensation for proper development. PTHrP secretion by epithelial cells of dermal mesenchyme induces differentiation to mammary mesenchyme, which maintains fate of epithelial cells, triggers morphogenesis, and stimulates nipple formation. No PTHrP = failure to differentiate (Blomstrands chondroplasia aka amastia). Temporary, GnRH drive, spike in progesterone during infancy stimulates branching/lobule formation–progesterone receptors in glandular elements up to 3 months post birth
- Puberty- glands start to form; get elaboration of ductal network driven by estrogen/progesterone. Way more acini/lobules and ductal regions extend out to limits of fat pad. Ductal growth primarily in follicular phase (estrogen), vs alveoli (progesterone) more in luteal phase
- secretory differentiation (lactogenesis 1 and 2)
- lactation
- involution: apoptosis/glandular regression and return to quiescence
What are the different breast tanner stages
Generally 11-15; macroscopic development due to an increase in breast accumulation. Functional development continues on past 15
1- slight elevation of nipple only (pre-adolescent)
2 - breast bud appears as small mound that is palpable. Areola enlarge and nipple remains elevated
3- Enlargement/levation of breast and areola without separation of their contours
4- Areola/nipples projected to form secondary mound with nipple and breast contours separated.
5- mature breast with areola receding to same contours as the breast and strongly pigmented
Witches milk
when elevated prolactin and decreased progesterone at parturition can induce temporary milk secretion in both female and male neonates
Hormonal changes during pregnancy
Development in Pregnancy: extensive lobular formation, differentiation of alveolar cells, minimal/no milk secretion.
Hormone regulators: Ovaries/placenta (estrogen, progesterone, placental latogen), pituitary (prolactin)
Hormones(lots produced by placenta): chorionic gonadotropin, placental lactogen (prolactin-like hormone), chorionic ACTH, PTHrP, growth hormone, progesterone, estrogen
PROGESTERONE = super important. required for formation of lobules
PROLACTIN- cooperates with progesterone in producing side-branching
- milk product synthesis initiated during pregnancy by prolactin/placental lactogen but secretion in check by high progesterone
Hormonal regulation of lactation
- milk secretion initiated by fall in progesterone at parturition– REMOVAL OF PLACENTA
- Also need elevated prolactin levels needed to maintain milk synthesis/secretion
- if small amount of placenta left behind, can inhibit lactation
Neuroendocrine feedback loop for lactation- suckling regulation of prolactin
Prolactin responsible for secretion
Prolactin stimulates synthesis/secretion of milk!
- Suckling stimulates afferent activation of hypothalamus (inhibits dopamine release). Less dopamine inhibiting prolactin release, so prolactin released from lactotrophs of anterior pituitary. Prolactin acts on breast for milk secretion.
- Prolactin = pulsatile secretion; pulse size/frequency regulated by suckling stimulus. More suckling = more production
- failure to initiate breastfeeding shortly after parturition diminishes prolactin signaling and impairs milk synthesis/secretion
- particular problem for women that deliver preterm infants as milk production capacity of mother and suckling ability of baby both immature (milk pump, breast milk bank)
- Activation of central dopaminergic pathways impairs lactation (i.e. Dopamine agonist bromocriptine)
- nursing stimulus downregulates GnRH and thus ovarian hormones, so less likely to get pregnant while breastfeeding
Neuroendocrien feedbackl oop- oxytocin
Oxytocin required for milk ejection
- Produced by posterior pituitary. Suckling stimulates synthesis/release of oxytocin from projections originally from hypothalamus that go into posterior pituitary and synapse on vessels in post. pituitary
- stimulates contraction of myoepithelial cells that form basket-like network around alveoli
can produce all you want but need to get it out to baby!
