Mammary gland

The mammary glands are arranged in organs such as the breasts in primates (for example, humans and chimpanzees), the udder in ruminants (for example, cows, goats, sheep, and deer), and the dugs of other animals (for example, dogs and cats).

The myoepithelial cells contract under the stimulation of oxytocin, excreting the milk secreted by alveolar units into the lobule lumen toward the nipple.

In this stage, mammary gland development depends on systemic (and maternal) hormones,[6] but is also under the (local) regulation of paracrine communication between neighboring epithelial and mesenchymal cells by parathyroid hormone-related protein (PTHrP).

[13] A basement membrane, mainly containing laminin and collagen, formed afterward by differentiated myoepithelial cells, keeps the polarity of this primary duct tree.

[14] Estrogen and growth hormone (GH) are essential for the ductal component of mammary gland development, and act synergistically to mediate it.

[27] During pregnancy, progesterone and prolactin are essential for mediating lobuloalveolar development in estrogen-primed mammary gland tissue, which occurs in preparation of lactation and nursing.

During puberty, tubule formation is coupled with branching morphogenesis which establishes the basic arboreal network of ducts emanating from the nipple.

Initially, the formation of the milk lines that run between the fore and hind limbs bilaterally on each side of the midline occurs around embryonic day 10.5 (E10.5).

Lastly, the third stage occurs at E12.5 and involves the invagination of cells within the placode into the mesenchyme, leading to a mammary anlage (biology).

Then, starting around four weeks of age, mammary ductal growth increases significantly with the ducts invading towards the lymph node.

Terminal end buds, the highly proliferative structures found at the tips of the invading ducts, expand and increase greatly during this stage.

Ductal development decreases with the arrival of sexual maturity and undergoes estrous cycles (proestrus, estrus, metestrus, and diestrus).

As a result of estrous cycling, the mammary gland undergoes dynamic changes where cells proliferate and then regress in an ordered fashion.

[36] During pregnancy, the ductal systems undergo rapid proliferation and form alveolar structures within the branches to be used for milk production.

These processes are tightly modulated by components of mammary epithelial ECM interacting with systemic hormones and local secreting factors.

[39] Important players include beta-1 integrin, epidermal growth factor receptor (EGFR), 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.

[40][41] 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.

[44] 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.

[45][46] When the lactiferous duct tree is almost ready, "leaves" alveoli are differentiated from luminal epithelial cells and added at the end of each branch.

[47][48] Their binding ensures correct placement of prolactin receptors on the basal lateral side of alveoli cells and directional secretion of milk into lactiferous ducts.

In this combined control from ECM and systemic hormones, milk secretion can be reciprocally amplified so as to provide enough nutrition for the baby.

[49] In some other species (such as cows), all alveoli and secretory duct structures collapse by programmed cell death (apoptosis) and autophagy for lack of growth promoting factors either from the ECM or circulating hormones.

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.

[66] 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.

Normal histology of the breast.
Light micrograph of a human proliferating mammary gland during estrous cycle. Sprouting gland tissue can be seen in the upper left field (haematoxylin eosin staining)