Breast Physiology and Histology Flashcards
What’s the biggest difference between healthy and cancerous breast cell proliferation?
Healthy: separation between steroid receptor expression and proliferation (steroid cells send paracrine signals that induce adjacent cells to proliferate)
Cancerous: ER+/PR+ cells proliferate on their own (autocrine/autonomous proliferation)
What are SERMs?
Selective Estrogen Response Modulators
- bind to estrogen receptors but final response is tissue specific (can be agonists or antagonists)
What hormones inhibit lactation during pregnancy? Does prolactin concentration increase during pregnancy even if there’s no lactation?
Estrogen and progesterone
YES! (by estradiol)
What secretes prolactin (PRL)? Inhibited by?
Negative feedback loop for PRL?
Secretion is by lactotrophs in the anterior pituitary
Tonic inhibition by dopamine (increased suckling = decreased dopamine = increased prolactin) – there’s no negative feedback loop for PRL
How does prolactin stimulate milk synthesis?
Binds to receptors on breast epithelial cells – prolactin receptors dimerize = induce synthesis of milk proteins (ex: casein)
Describe how suckling results in oxytocin release?
suckling/other neural cues – dorsal horn of spinal cord – brainstem – medial forebrain bundle – activation of magnocellular neurons PVN and SON – release of oxytocin from the posterior pituitary
Prolactin and Oxytocin both increase in response to suckling but how is their timing different?
Prolactin is secreted ONLY in response to suckling; oxytocin can be secreted in response to other cues also
Oxytocin causes contractions of what cells?
Myoepithelial cells
What are the 5 main mechanisms of milk synthesis and secretion (just the names)?
- Exocytosis of milk components
- Apical secretion of Ions
- Apocrine Secretion of Fat
- Transcellular secretion of immunoglobulins, proteins
- Paracellular passage of cells, some plasma components
Describe the synthesis of calcium for milk (PTH-RP, CASR)
- lactating breast cells make PTH-RP = causes maternal bone to release calcium that is then pumped into the mammary cells against concentration gradient
- calcium sensing receptor (CASR) on the breast cells regulates PTH-RP
Describe fat addition/synthesis in milk
Fat is made in mammary cells - added to milk at later feeding in response to PRL through apocrine secretion
What is the only ion that the mammary gland reabsorbs from milk?
Sodium! (milk is hypotonic with respect to plasma sodium concentration)
- alveolar cells don’t typically absorb things once they’ve been secreted into milk
Describe the secretion of immunoglobulins into milk
Alveolar cells uptake immunoglobulins through pinocytosis (transcellular transport) and exit via exocytosis
Describe the transport of immune cells into milk
Paracellular: tight junctions seal behind them, preventing the transport of non-selective things
Why would lactation prevent ovarian cancer?
Reduced number of ovulations over lifetime = less damage to ovarian surface
Why would lactation protect against breast cancer?
Lactational amenorrhea and low levels of estradiol/progesterone
When is colostrum secreted? It’s high in?
1st postpartum week
High in immunoglobulins, immune cells, protein, fat-soluble vitamins, minerals
When is transitional milk secreted? Content?
7 - 14 days post-partum
Increasing lactose, water-soluble vitamins, fat, total calories
Content of mature milk
Rich in lipids, CHO (mainly lactose)
How does breast milk composition change during a single feeding?
Early in the feed ("fore milk"): greatest milk volume; little fat, lactose rich
Later on ("hind milk"): greatest caloric value (when lipids are added in response to PRL)What are the 4 components of the breast?
Nipple-areolar complex, ductal system, glands, fibroadipose tissue
From what 2 places do breast tumors arise and what percentage?
Ductal epithelium (90%) Lobar alveolar ductal epithelium (10%)
What is the terminal duct lobular unit (TDLU)?
Functional unit of milk production
- 20 - 40 lobes organized as alveoli, ducts, intralobular connective tissue
What are the 4 steps of breast development? (no difference between genders!)
- Epithelium down-growth as primary mammary bud
- Branching of secondary buds stimulated by mesenchymal cells
- Lumen develops
- Luminal epithelial cells differentiate
Roles of estrogen during breast remodeling at puberty
Stimulates lactiferous duct development
Roles of progesterone during breast remodeling at puberty
Stimulates development of new alveolar buds
Roles of prolactin during breast remodeling at puberty
Steroid hormone effects
Changes during pregnancy regarding lobular size and fat
Increased lobular size
Decreased lobular fat in intralobular connective tissue
Changes during 1st trimester regarding terminal ductules and epithelial/myoepithelial cells
- terminal ductules: elongate and branch
- cells proliferate and differentiate from progenitor cells
Changes during 2nd trimester regarding alveoli and immune cells
- alveoli: differentiate from the growing ends of the terminal ductules
- immune cells: infiltrate intralobular connective tissue
Changes during 3rd trimester regarding alveoli, TDLU vascularity, interlobular stroma, secretory cells
- alveoli: develop rER, secretory granules, lipid droplets
- increased vascularity in TDLU
- stroma: regresses
- secretory cells: proliferate
Apocrine vs. merocrine secretion
- apocrine: plasma membrane forms the vesicles
- merocrine: exocytosis from secretory cells
What are the 4 main changes that occur as the breasts begin to age during the third decade of life?
- Loss of elasticity
- Increased adipose tissue
- Few TDLUs
- Regression of lobules via apoptosis
