Mammary gland Flashcards
monotremes
- prototherians: platypus, echidna)
- lay eggs, very altricial young
- do not have nipples –> mammary glands discharge directly onto specialized area of skin (areola) from where the young suck or lick it up
marsupials
- metatheria
- short gestation period (length of luteal phase of estrous cycle)
- young born at an immature, almost embryonic stage
- following birth, they climb to pouch, attach to nipple (swells, fixed to it)
eutherians
- true placental mammals
- neonatal development varies from altricial to precocious but are all dependent on milk for earl y part of post-uterine life
number of mammary glands
varies from 2 (1 pair) in humans, sheep, goats up to 18 (9 pairs) in the sow
positioning of mammary glands
- thorax (primates, elephants, bats)
- abdominal (whales)
- inguinal (cow, goat, sheep)
- along ventral thorax/abdomen/inguinal region (sow, rat, rabbit)
- almost dorsal (coypu)
- determined during embryonic development
shape of mammary glands
- ranges from flattened sheets, flat but circular, prominent, dependent
- all females except monotremes have nipples/teats
- absent in males in some species
2 basic tissue types
- parenchyma (secretory)
- supporting tissue (stroma)
structure of milk secreting tissue
- similar across species
- basic structure = alveolus
- sack lined by single layer of secretory epithelial cells, outside is myoepithelial layer, then basement membrane, then capillaries
- secretion through capillary milk duct
alveoli arrangement
- arranged in groups called lobules
- individual capillary milk ducts empty into intralobular ducts
- enter progressively larger ducts
- each lobule surrounded by CT
- groups of lobules = lobes
how are differences in mammary glands manifested
in anatomy and arrangement of duct system
ducts in dogs and humans
12-20 major ducts have openings on each nipple
ducts in cow, goat, sheep
- major ducts empty into a large gland cistern, which is continuous with the teat cistern
- this is drained via the single streak canal
ducts in mare and sow
- 2 glad systems, with relatively small glands, are drained into a single teat
- teat has 2 openings or streak canals (one for each gland system)
galactophores
ducts discharging at the nipple (or skin in monotremes)
what is outside glandular tissue
- stroma (mix of CT and fat cells) –> mammary fat pad
- supporting tissue for parenchymal development
cow supporting mammary gland structures
- udder divided into L and R halves by median suspensory ligament (elastin and collagen)
- elastin predominates –> shock absorber
- lateral suspensory ligaments, lamellar plates
- skin is infection barrier
embryonic mammary development
- mammary glands derived from embryonic ectoderm
- development begins as bilateral linear thickening of ectoderm
- become discontinuous to finish as mammary buds (grow into underlying mesoderm)
fetal development - primary cord
- after mammary bud attains spherical shape
- groups of cells proliferate out of the sphere and form cords of cells that elongate deeper into dermal tissue to form primary cord
- number of primary cords that grow out of each bud determine the number of ducts that will open onto the nipple
fetal development - secondary cords
- once primary cord attains certain size, distal end branches to form 2 or more secondary buds
- these elongate into cords that eventually form large milk ducts
- ruminants: they discharge into gland cistern
fetal development - canalization of the cords
- when cords elongating, also increase in diameter
- result is cells in center of cord get farther away from nutrient source and die
- cords become hollow and form mammary ducts
fetal development - supporting tissue
- CT supporting structures for mammary gland
- heifer: growth of 4 glands and fat pads, median suspensory ligament, 4 distinct quarters
what is development of mammary gland controlled by
factors from the local mesenchyme
what happens when you remove mammary mesenchyme
no formation of the mammary gland
development of mammary fat pad
- early in development: layer of adipose tissue cells surround mammary bud
- adequately formed fat pad is necessary for successful progression of mammary growth
ovarian factors in mammary gland development
no requirement for ovarian factors (steroid hormones) in the development of the mammary glands during fetal life
testosterone in male rat fetuses
influence of testosterone in male fetuses causes the primary mammary cord to lose its attachment to the surface epithelium during later fetal life –> male mice/rats have no nipples (same with horses, beavers)
mammary development at birth
- mammary gland consists of rudimentary duct system that opens at a small nipple
- gland shows general growth at an isometric rate (same as body)
mammary development at puberty
- several weeks before: growth of mammary gland becomes allometric (faster than general body growth)
- due to increased secretion of ovarian hormones (estrogen) from developing follicles
mammary development following puberty
- ultrashort cycles (mice): mostly duct growth, alveoli rarely formed
- long cycle, full luteal (primates) and short cycle: duct development is almost full - formation of fine ductules that indicate future lobules, few alveoli
- pseudopregnancy (bitch): duct growth accompanied by considerable lobulo-alveolar development - only seen during pregnancy in other species
when does full alveolar development occur in monotremes
in response to egg incubation
when does full development of mammary gland occur in eutherian mammals
- only completed during pregnancy or early lactation
- growth of gland during pregnancy fits exponential curve (growth rate inversely proportional to gestation length)
- more lobulo-alveolar development in 2nd half of pregnancy
development of mammary gland in eutherian mammals during pregnancy
- mammary fat pad slowly infiltrated, adipose tissue replaced by duct tissue, alveoli, lymphatic vessels, CT structures
- alveoli arranged in lobules take over much of gland volume
- stroma represented by thin bands of CT that divide lobules and regions of lobules into lobes
when do alveolar cells begin to secrete
- ruminants: last third of pregnancy, alveolar lumen becomes distended
- other species: no secretion until just before parturition
- all species: burst of secretory activity just prior to and just after parturition
what holds full secretory activity in check before parturition
high circulating progesterone levels
what body tissue has growth and function most regulated by hormones
mammary gland
what hormones does duct growth depend on
- estrogen
- adrenal steroids
- growth hormone
what hormones does lobulo-alveolar growth require
- estrogen
- adrenal steroids
- growth hormone
- progesterone
- prolactin
what are placental lactogens and what are they important for
- prolactin-like hormones produced in placenta
- important role in mammary growth during pregnancy
differentiation of alveolar epithelial (secretory) cells near parturition
- nucleus moves to basal area, becomes rounded
- base/lateral areas of cell filled with RER and small lipid droplets
- apical area becomes filled with swollen golgi membrane arrays, secretory vesicles, small lipid droplets
what happens to microscopic appearance of aveolar epithelial (secretory) cells near parturition
- apical areas appear lacy/foamy
- basolateral areas darkly stained
polarization of alveolar epithelial (secretory) cells near parturition
- basal area concerned with precursor uptake and synthesis of protein, lipid
- apical area performing posttranslational modification of proteins, packaging of these proteins/lactose ready for secretion
general model for lactation induction at the end of parturition
- increase of positive stimulators for lactation
- decline in lactogenic enzyme inhibitor
positive stimulators for lactation
- prolactin, glucocorticoids, estradiol, growth hormone +/- insulin
- increase in mammary sensitivity to them
lactogenic enzyme inhibitor
progesterone
what does milk composition depend on
- amount and type of precursors taken up by the gland
- transformation they undergo during milk synthesis
what are major substrates extracted from the blood by mammary cells
- glucose
- amino acids
- fatty acids
- minerals
- ruminants: acetate, b-hydroxybutyrate
main precursor for fatty acid production in monogastrics v ruminants
- mono: glucose
- ruminants: propionate (acetate) –> glucose used for lactose production
what is major sugar in milk and its composition
lactose = glucose + galactose
how and where is lactose synthesized
- synthesized in the mammary gland from glucose supplied by bloodstream
- cow: glucose made in liver by gluconeogenesis
what is lactose synthesized from
from glucose by enzyme complex lactose synthetase (galactosyltransferase + a-lactalbumin)
what happens when glucose and UDP-galactose enter golgi
form lactose and UDP under influence of lactse synthase complex
what is golgi membrane permeable/impermeable to and why is this important
- permeable to glucose/galactose (monosaccharides), impermeable to lactose (disaccharide)
- surgar is major osmotically active component of milk, draws water into golgi vesicle –> accounts for milk volume
what does milk protein consist of
- caseins, a-lactalbumin, b-lactoglobulin, serum albumin, lactoferrin, lysozyme, immunoglobulins, NPN compounds
- casein, a-lactalbumin, b-lactoglobulin are >90% of protein in most species ( more lactoferrin, NPN)
what provide building blocks for milk protein synthesis
amino acids, NPN compounds from blood
where are proteins made and transported to
- proteins assembled on surface ribosomes of RER
- inserted into lumen of ER
- transported to golgi
- micelles secreted from golgi
what types of lipids are present in milk
- 97-98% triglycerides
- remainder are mostly phospholipids
milk fatty acids
- C4 to C18
- under C16 synthesized in mammary alveolar epithelia cells, greater than or equal to C16 derived from blood borne lipids
what are precursors for lipid formation in ruminants, non-ruminants
- ruminants: acetate, b-hydroxybutyrate, triacylglycerides
- nonruminants: glucose, triacylglycerides
list 5 pathways for secretion of components into milk
- exocytosis
- reverse pinocytosis
- transmembrane transport
- transcytosis
- paracellular transport
exocytosis pathway for secretion of milk components
- proteins, lactose, salts, non-fat components packaged into secretory vesicles in golgi
- vesicles bud off from golgi, move to cell apex
- membrane surrounding vesicle fuses with plasma membrane, contents released into alveolar lumen
reverse pinocytosis pathway for secretion of milk components
- lipid droplets form near ER, transported to apical membrane
- membrane forms milk fat globule membrane –> membrane pinches off beneath it
- globule secreted into alveolar lumen
transmembrane transport pathway for secretion of milk components
- other salts pumped into cell at base, some passively diffuse into alveolus
- apical plasma membrane permeable to monovalent ions (Na, Cl, K), and glucose
- impermeable to divalent cations, disaccharides
- diffusion and pumping across basal and apical membranes
transcytosis pathway for secretion of milk components
- mechanism for proteins that are not synthesized in the alveolar epithelial cell to enter the milk (IgA, insulin, prolactin, IGF-1, albumin)
- protein interacts with receptor at basal membrane
- protein-receptor complex internalized, transported across cell to apical membrane where protein are released into alveolar lumen
paracellular transport pathway for secretion of milk components
- lactation: tight junctions form between adjacent mammary epithelial cells - separate interstitial spaces and alveolar lumen (close paracellular transport)
- pregnancy: tight junctions open, large proteins can be transported this way
in lab animals, what are the minimum requirements for continued lactation
- prolactin
- corticosteroids
- oxytocin
purpose of glucocorticoids in non-ruminants
- regulate activity of enzymes in milk synthesis pathway by controlling their transcription rates
- adrenalectomy causes 50% drop in milk production
functions of prolactin in non-ruminants
- maintain enzyme levels and protein synthesis
- increases gene transcription rates and half-lives of resulting mRNAs
- effect is enhanced by glucocorticoids
- prevents apoptosis of mammary epithelium, maintains tight junctions
effects of adrenalectomy on ruminant lactation
none or very minimal –> no requirement for glucocortioids
what is main requirement for lactation maintenance in ruminants and what does it do
- somatotropin (growth hormone)
- maintains mammary secretory cell numbers, greater rate of milk synthesis
- acts directly on mammary gland, increases IGF production in liver
importance of prolactin in ruminant lactation
- controversial
- role in mammary epithelial cell proliferation, function, prevention of apoptosis
function of oxytocin in lactation maintenance
- required for removal of milk from alveolus
- mammary glands degenerate without it
- repeated suckling/milking is necessary
function of frequency of milk removal
- increasing frequency of milk removal increases milk production
- cows: acute and sustained effect (3 week window at beginning of lactation where you set potential)
controls for local effects of control of milk synthesis
- sustained one involves changes in genetic imprinting
- acute chages: feedback inhibitor of lactation (FIL), casein fragments, serotonin
what is feedback inhibitor of lactation (FIL)
- autocrine regulator –> inhibits same cell that secretes it
- binds to receptor on apical plasma membrane and has immediate effects to inhibit protein/lactose secretion
milk storage
- secreted continuously, stored within the lumen of the alveolus and expansions of duct system
- duct system large in ruminants, none in rat/rabbit, small in women
milk passive/active ejection
- milk in storage ducts available passively to suckling/milk machine
- milk in alveoli/smaller ducts needs active ejection (majority of it)
what is milk ejection controlled by
neuroendocrine reflex
how is nipple innervated
intradermal sensory afferent nerves
after nipple sensory afferent nerves synapse with nerves in spinal cord, where do they do
synaptic relays –> hypothalamus –> paraventricular/supraoptic nuclei (contain oxytocin producing neurons) –> posterior pituitary releases oxytocin
purpose of oxytocin in milk ejection
-circulates in blood and causes contraction of myoepithelial cells –> ejects milk from alveoli into duct system
conditioning of milk ejection reflex
- may be conditioned to other stimuli (cows seeing milking parlor)
- can be inhibited by stressful situations due to central abolition of oxytocin release
