Lecture 43 Flashcards
Mammary Gland
Compound tubuloalveolar gland with 15-20 lobes, derived from modified apocrine sweat glands
- each lobe opens separately rather than having 1 common duct.
- the diff lactiferous ducts open separately on the nipple.
Has: lactiferous sinus, lactiferous duct, lobule, dense connective and adipose tissue, areola, nipple
Development of mammary gland
- Dermal mesenchymal cells secrete cytokines to induce formation of epithelial bud
- Adipose cells stimulate branching of solid epithelial mammary cords
- mammary gland is developed from apocrine sweat glands - Mammary cords become hollow. Also, some luminal epithelial cells differentiate into myoepithelial cells
Ep cells that form a duct system develop into 2 diff cell types:
- cells that line the duct and alveolus (secretory portion of gland)
- myoepithelial cells (similar to sweat glands)
Luminal cells and myoepithelial cells of mammary gland
Ep bud has leading cells that migrate and invade CT. This is how the mammary gland gets bigger or branches.
- At furthest end of bud, ep cells die via apoptosis, resulting in a lumen.
- Also, at end of bud, Cap cells divide and differentiate into luminal cells and myoiepithelial cells
- luminal cells either modify the secretion or actually secrete
- myoepithelial cells surround outside of luminal cells
Mouse mammary gland
- good to study morphogenesis and branching morphogenesis of glands and cancers
- used for studies
H and E:
- ep buds migrate into the CT and branch
- the duct system then forms a branching network that sends secretions and milk into a common lactiferous duct.
- large brown spots are lymph nodes
Terminal duct lobular unit
Developing mammary gland has lots of terminal duct lobular units (later involved in milk production)
All alveoli within lobular unit drains into common terminal duct, which then drains into a larger duct called lactiferous duct (wide and has stratified cuboidal ep)
H and E: Terminal duct lobular unit
Cross sec: dark-stained groups of cells.
There is also lighter-stained loose CT, which represents papillary layer of skin and is
called intralobular loose CT.
There is lactiferous duct with big lumen
On outside, there is interlobular dense connective tissue
Nipple
Lactiferous ducts merge into larger area called lactiferous sinus (Stratified cuboidal epithelium). The sinus is right underneath the areola of the nipple.
Nipple purpose is to allow accumulation of milk, so when the baby sucks, it gets rewarded by milk
Nipple is also filled with bundles of smooth muscle.
- smooth muscle bundles run in diff orientations, surrounded by DICT
there are sebaceous glands associated with the nipple.
Glands of Montgomery
- Bumps around nipple are glands that contain glycoprotein and phospholipid secretions
Sebaceaous glands:
• Not associated with hair follicles
• Lubricate nipple
• Secrete volatile compounds that stimulate the baby to suckle
• Anti-microbial substances to fight infections
Mammary gland at puberty and pregnancy
Before puberty:
- mammary gland in male and females look identical.
- Initially, we have rudimentary duct system developing, but then it stops. in h and E,
In females during puberty:
- estrogen, progesterone and prolactin are
secreted, which stimulates branching and development of the duct.
- estrogen is responsible for elongation of duct system
- progesterone makes alveolar buds, maintained by progesterone.
- surrounding fat or adipose tissue is under influence of estrogen and progesterone
Size of breast is not related to how much glandular tissue there is, but the amount of CT and fat.
During pregnancy:
- prolactin and placental hormones cause changes in lobules and some CT is disassembled to make room for the expansion of the lobules
- the breast gets bigger due to enlargement of lobules
Mouse mammary gland
Pre-puberty (4 weeks): rudimentary duct system
- dormant, same in male and female
Mid puberty (6 weeks): duct elongation - also has increase in terminal duct lobular units
Adult virgin (10 weeks): duct branching
Inactive resting mammary gland
The duct system of an inactive gland blindly ends in small alveoli
- A lobule consists of one terminal duct branching into several alveoli
H and E: cross sec of ducts and a significant amount of glandular tissue surrounded by CT and adipose tissue.
This is after puberty
Mammary gland in non-pregnant, pregnant and lactation
Amount of glandular tissue increases at expense of CT
In non-pregnant women, the gland has an inactive duct system
- 50:50 ratio of CT and glands
During pregnancy, alveoli proliferate at the ends of ducts and produce colostrum
- amount of glandular tissue increases a lot, and decrease of CT.
- 2/3 are glands, 1/3 are CT
During lactation, alveoli are fully differentiated with abundant milk secretion
- after birth of baby, as mammary gland gets active, the wall bw the filled secretory units is very thin and lots of secretion accumulate within alveoli.
- amount of CT is very thin
Mouse mammary gland during pregnancy
Early Pregnancy: Side Branching
- groups of lil alveoli in early pregnancy
Mid Pregnancy: Alveologenesis
- amount of alveoli increase
Post-partum: Lactation
- as alveoli secretes product, the product fills in the alveoli and increases the glandular tissue
Mammary gland at early pregnancy
Proliferation of ducts and formation of secretory alveoli
- most of the slide occupied by ep cells and glandular tissue
Mammary gland at late pregnancy
Prolactin stimulates secretion of colostrum and milk by alveolar cells
Distended alveoli
Lumens develop within the alveoli. the cell starts secreting material and expands the glandular tissue. Can now can distinguish bw ducts and ep cells that line a space.
Lactiferous duct filled with secretion
No milk production yet
Lactating mammary gland
Distended alveoli
Lumen of alveoli got bigger.
Wall spaces get very thin, very little CT
too
Lactation steps
- Mammogenesis: stimulated during pregnancy by estrogen and progesterone, acting together with prolactin
- Lactogenesis: stimulated after parturition (childbirth) by prolactin
- prolactin releasing factor in hypothalamus is sent to acidophilic mammotrophs, which make prolactin
- prolactin goes to systemic circulation and is for lactation - Galactopoiesis (maintenance of lactation once lactation has been established): stimulated by prolactin and oxytocin
- as long as a baby sucks, signals will be sent to hypothalamus that continuously
produces regulators for prolactin production
Within alveoli of mammary gland
PROLACTIN:
- stimulates milk production
- cells have prolactin receptors
- regulates the below last 4 components
OXYTOCIN:
- stimulates milk release by inducing contraction of myoepithelial cells
- myoepithelial cells surround alveoli and have oxytocin receptors, which receive oxytocin from pituitary gland. This allows myoepithelial cells to contract, forcing delivery of material
- crying of other babies can stimulate woman’s hypothalamus to release
oxytocin, which causes lactation to random babies. This is called milk letdown reflex
Milk contains: sugars (lactose), proteins, lipids and antibodies (IgA)
LIPIDS:
- released, surrounded by a rim of cytoplasm (apocrine secretion)
- lipid droplets that accumulate in cytoplasm will be pushed outward, and leave the cell with a little bit of cytoplasm and plasma membrane
LACTOSE:
- produced in the Golgi and secreted as vesicles by a merocrine mechanism
PROTEINS:
- made in RER
- (casein, lactalbumin) secreted as vesicles by a merocrine mechanism
IgA:
- produced by plasma cells
- is shuttled across the epithelium, then are put in vesicles and released in components in milk
Myoepithelial cells
Secretory acini are surrounded by contractile stellate Myoepithelial Cells. They contract upon stimulation with oxytocin, moving secretory products into the duct system.
Smooth Muscle alpha actin
Image: meshwork of cells stained for filamentous actin, and these are responsible for delivering content to surface
Oxytocin
Paraventricular nucleus is the one that mostly makes oxytocin (some vasopressin too) and this is delivered into the pars nervosa where it enters capillaries to contract the myoepithelial cells
Oxytocin is released by the Pars Nervosa (Neurohypophysis) of the Pituitary Gland
Breast cancer: ductal carcinoma
Ducts within mammary gland: Normal duct to ductal hyperplasia to atypical hyperplasia to DCIS to invasive ductal carcinoma
The cells become atypical, start proliferating and fill in the lumen.
As long as the abnormal cells stay within the lumen of the duct, this is a good sign bc they
have not metastasized, and they can be excised or treated.
HOWEVER, once the cells break through the basement membrane, reach CT and find
an area to expand, it is called invasive ductal carcinoma, which is not a good prognosis. These cells find themselves in lymph node
In your office a 24 year old mother expresses her fear that she may not be able to have other children after the birth of her son 18 months ago, because she has not had regular menstrual cycles since. Upon inquiry you learn that she is still fully breast-feeding her infant. You explain to her that her irregularity is called “lactational amenorrhea” and is caused by:
A. Lack of prolactin secretion by the mammary gland
B. Over-production of estrogen due to lactation
C. Release of Oxytocin by the pituitary gland
D. Prolactin secretion by the pituitary gland
E. Continued activity of myoepithelial cells
D
high prolactin levels suppress estrogen and progesterone release from ovarian follicles
