A mammary gland is an organ in female mammals that produces milk to feed young offspring.
Mammals get their name from the word "mammary." In humans, the mammary glands are situated
in the breasts. In ruminants such as cows, goats, and deer, the mammary glands are contained
in the udders. The mammary glands of mammals other than primates, such as dogs and cats,
are sometimes called dugs.
Structure
The basic components of a mature mammary gland are the alveoli lined with milk-secreting
cuboidal cells and surrounded by myoepithelial cells. These alveoli join to form groups known
as lobules. Each lobule has a lactiferous duct that drains into openings in the nipple.
The myoepithelial cells contract under the stimulation of oxytocin, excreting the milk
secreted by alveolar units into the lobule lumen toward the nipple. As the infant begins
to suck, the oxytocin-mediated "let down reflex" ensues and the mother's milk is secreted – not
sucked from the gland – into the baby's mouth.
All the milk-secreting tissue leading to a single lactiferous duct is called a "simple
mammary gland"; in a "complex mammary gland" all the simple mammary glands serve one nipple.
Humans normally have two complex mammary glands, one in each breast, and each complex mammary
gland consists of 10–20 simple glands. The presence of more than two nipples is known
as polythelia and the presence of more than two complex mammary glands as polymastia.
Maintaining the correct polarized morphology of the lactiferous duct tree requires another
essential component – mammary epithelial cells extracellular matrix which, together
with adipocytes, fibroblast, inflammatory cells, and others, constitute mammary stroma.
Mammary epithelial ECM mainly contains myoepithelial basement membrane and the connective tissue.
They not only help to support mammary basic structure, but also serve as a communicating
bridge between mammary epithelia and their local and global environment throughout this
organ's development. Histology
A mammary gland is a specific type of apocrine gland specialized for manufacture of colostrum
when giving birth. Mammary glands can be identified as apocrine because they exhibit striking
"decapitation" secretion. Many sources assert that mammary glands are modified sweat glands.
Some authors dispute that and argue instead that they are sebaceous glands.
Development
Mammary glands develop during different growth cycles. They exist in both sexes during embryonic
stage, forming only a rudimentary duct tree at birth. In this stage, mammary gland development
depends on systemic hormones, but is also under the regulation of paracrine communication
between neighboring epithelial and mesenchymal cells by parathyroid hormone-related protein(PTHrP).
This locally secreted factor gives rise to a series of outside-in and inside-out positive
feedback between these two types of cells, so that mammary bud epithelial cells can proliferate
and sprout down into the mesenchymal layer until they reach the fat pad to begin the
first round of branching. At the same time, the embryonic mesenchymal cells around the
epithelial bud receive secreting factors activated by PTHrP, such as BMP4. These mesenchymal
cells can transform into a dense, mammary-specific mesenchyme, which later develop into connective
tissue with fibrous threads, forming blood vessels and the lymph system. A basement membrane,
mainly containing laminin and collagen, formed afterward by differentiated myoepithelial
cells, keeps the polarity of this primary duct tree.
Physiology Hormonal control
Lactiferous duct development occurs in females in response to circulating hormones. First
development is frequently seen during pre- and postnatal stages, and later during puberty.
Estrogen promotes branching differentiation, whereas in males testosterone inhibits it.
A mature duct tree reaching the limit of the fat pad of the mammary gland comes into being
by bifurcation of duct terminal end buds, secondary branches sprouting from primary
ducts and proper duct lumen formation. These processes are tightly modulated by components
of mammary epithelial ECM interacting with systemic hormones and local secreting factors.
However, for each mechanism the epithelial cells' "niche" can be delicately unique with
different membrane receptor profiles and basement membrane thickness from specific branching
area to area, so as to regulate cell growth or differentiation sub-locally. Important
players include beta-1 integrin, epidermal growth factor receptor, laminin-1/5, collagen-IV,
matrix metalloproteinase(MMPs), heparan sulfate proteoglycans, and others. Elevated circulating
level of growth hormone and estrogen get to multipotent cap cells on TEB tips through
a thin, leaky layer of basement membrane. These hormones promote specific gene expression.
Hence cap cells can differentiate into myoepithelial and luminal epithelial cells, and the increased
amount of activated MMPs can degrade surrounding ECM helping duct buds to reach further in
the fat pads. On the other hand, basement membrane along the mature mammary ducts is
thicker, with strong adhesion to epithelial cells via binding to integrin and non-integrin
receptors. When side branches develop, it is a much more “pushing-forward” working
process including extending through myoepithelial cells, degrading basement membrane and then
invading into a periductal layer of fibrous stromal tissue. Degraded basement membrane
fragments roles to lead the way of mammary epithelial cells migration. Whereas, laminin-1
interacts with non-integrin receptor dystroglycan negatively regulates this side branching process
in case of cancer. These complex "Yin-yang" balancing crosstalks between mammary ECM and
epithelial cells "instruct" healthy mammary gland development until adult.
There is preliminary evidence that soybean intake mildly stimulates the breast glands
in pre- and postmenopausal women. Pregnancy
Secretory alveoli develop mainly in pregnancy, when rising levels of prolactin, estrogen,
and progesterone cause further branching, together with an increase in adipose tissue
and a richer blood flow. In gestation, serum progesterone remains at a stably high concentration
so signaling through its receptor is continuously activated. As one of the transcribed genes,
Wnts secreted from mammary epithelial cells act paracrinely to induce more neighboring
cells' branching. When the lactiferous duct tree is almost ready, "leaves" alveoli are
differentiated from luminal epithelial cells and added at the end of each branch. In late
pregnancy and for the first few days after giving birth, colostrum is secreted. Milk
secretion begins a few days later due to reduction in circulating progesterone and the presence
of another important hormone prolactin, which mediates further alveologenesis, milk protein
production, and regulates osmotic balance and tight junction function. Laminin and collagen
in myoepithelial basement membrane interacting with beta-1 integrin on epithelial surface
again, is essential in this process. Their binding ensures correct placement of prolactin
receptors on the basal lateral side of alveoli cells and directional secretion of milk into
lactiferous ducts. Suckling of the baby causes release of the hormone oxytocin, which stimulates
contraction of the myoepithelial cells. In this combined control from ECM and systemic
hormones, milk secretion can be reciprocally amplified so as to provide enough nutrition
for the baby. Weaning
During weaning, decreased prolactin, missing mechanical stimulation, and changes in osmotic
balance caused by milk stasis and leaking of tight junctions cause cessation of milk
production. In some species there is complete or partial involution of alveolar structures
after weaning, in humans there is only partial involution and the level of involution in
humans appears to be highly individual. The glands in the breast do secrete fluid also
in nonlactating women. In some other species, all alveoli and secretory duct structures
collapse by programmed cell death and autophagy for lack of growth promoting factors either
from the ECM or circulating hormones. At the same time, apoptosis of blood capillary endothelial
cells speeds up the regression of lactation ductal beds. Shrinkage of the mammary duct
tree and ECM remodeling by various proteinase is under the control of somatostatin and other
growth inhibiting hormones and local factors. This major structural change leads loose fat
tissue to fill the empty space afterward. But a functional lactiferous duct tree can
be formed again when a female is pregnant again.
Clinical significance Tumorigenesis in mammary glands can be induced
biochemically by abnormal expression level of circulating hormones or local ECM components,
or from a mechanical change in the tension of mammary stroma. Under either of the two
circumstances, mammary epithelial cells would grow out of control and eventually result
in cancer. Almost all instances of breast cancer originate in the lobules or ducts of
the mammary glands. Other mammals
General The constantly protruding breasts of the adult
human female, unusually large relative to body size, are a unique evolutionary development
whose purpose is not yet fully known; other mammals tend to have less conspicuous mammary
glands that protrude only while actually filling with milk. The number and positioning of complex
and simple mammary glands varies widely in different mammals. The nipples and glands
can occur anywhere along the two milk lines, two nearly parallel lines along the ventral
aspect of the body. In general most mammals develop mammary glands in pairs along these
lines, with a number approximating the number of young typically birthed at a time. The
number of nipples varies from 2 to 18. The Virginia Opossum has 13, one of the few mammals
with an odd number. The following table lists the number and position of glands normally
found in a range of mammals:
Male mammals typically have rudimentary mammary glands and nipples, with a few exceptions:
male mice do not have nipples, and male horses lack nipples and mammary glands. The male
Dayak fruit bat has lactating mammary glands. Male lactation occurs infrequently in some
species, including humans. Mammary glands are true protein factories,
and several labs have constructed transgenic animals, mainly goats and cows, to produce
proteins for pharmaceutical use. Complex glycoproteins such as monoclonal antibodies or antithrombin
cannot be produced by genetically engineered bacteria, and the production in live mammals
is much cheaper than the use of mammalian cell cultures.
Evolution The evolution of the mammary gland is difficult
to explain; this is because mammary glands are typically required by mammals to feed
their young. There are many theories on how mammary glands evolved, for example, it is
believed that the mammary gland is a transformed sweat gland, more closely related to apocrine
sweat glands. Since mammary glands do not fossilize well, supporting such theories with
fossil evidence is difficult. Many of the current theories are based on comparisons
between lines of living mammals – monotremes, marsupials and eutherians. One theory proposes
that mammary glands evolved from glands that were used to keep the eggs of early mammals
moist and free from infection. Other theories suggest that early secretions were used directly
by hatched young, or that the secretions were used by young to help them orient to their
mothers. Lactation is assumed to have developed long
before the evolution of the mammary gland and mammals; see evolution of lactation.
Additional images
See also This article uses anatomical terminology;
for an overview, see anatomical terminology. Breastfeeding
Mammary tumor Mammaglobin
Gynecomastia Udder
Witch's milk Milk line
List of specialized glands within the human integumentary system
References
Bibliography Ackerman, A. Bernard; Almut Böer; Bruce Bennin;
Geoffrey J. Gottlieb. Histologic Diagnosis of Inflammatory Skin Diseases An Algorithmic
Method Based on Pattern Analysis. ISBN 978-1-893357-25-9. Moore, Keith L. et al. Clinically Oriented
Anatomy 6th Ed External links
Comparative Mammary Gland Anatomy by W. L. Hurley
On the anatomy of the breast by Sir Astley Paston Cooper. Numerous drawings, in the public
domain. mammary+gland at eMedicine Dictionary