Mammary gland
A mammary gland is an exocrine gland that produces milk in mammals, including humans. Mammals get their name from the Latin word mamma, "breast". The mammary glands are arranged in organs such as the breasts in primates, the udder in ruminants, and the dugs of other animals to feed young offspring. Lactorrhea, the occasional production of milk by the glands, can occur in any mammal, but in most mammals, lactation, the production of enough milk for nursing, occurs only in phenotypic females who have gestated in recent months or years. It is directed by hormonal guidance from sex steroids. In a few mammalian species, male lactation can occur. With humans, male lactation can occur only under specific circumstances.
Mammals are divided into 3 groups: monotremes, metatherians, and eutherians. In the case of monotremes, their mammary glands are modified sebaceous glands and without nipples. Concerning most metatherians and eutherians, only females have functional mammary glands, with the exception of some bat species. Their mammary glands can be termed as breasts or udders. In the case of breasts, each mammary gland has its own nipple. In the case of udders, pairs of mammary glands comprise a single mass, with more than one nipple hanging from it. For instance, cows and buffalo udders have two pairs of mammary glands and four teats, whereas sheep and goat udders have one pair of mammary glands with two teats protruding from the udder. Each mammary gland produces milk for a single teat and is evolutionarily derived from modified sweat glands.
Structure
The basic components of a mature mammary gland are the alveoli, which are 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 infant's mouth.All the milk-secreting tissue leading to a single lactiferous duct is collectively 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 opening of each simple gland on the surface of the nipple is called a "pore." 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.Development
Mammary glands develop during different growth cycles. They exist in both sexes during the 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. 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. These components of the extracellular matrix are strong determinants of duct morphogenesis.Biochemistry
and growth hormone are essential for the ductal component of mammary gland development, and act synergistically to mediate it. Neither estrogen nor GH are capable of inducing ductal development without the other. The role of GH in ductal development has been found to be mostly mediated by its induction of the secretion of insulin-like growth factor 1, which occurs both systemically and locally in the mammary fat pad through activation of the growth hormone receptor. However, GH itself also acts independently of IGF-1 to stimulate ductal development by upregulating estrogen receptor expression in mammary gland tissue, which is a downstream effect of mammary gland GHR activation. In any case, unlike IGF-1, GH itself is not essential for mammary gland development, and IGF-1 in conjunction with estrogen can induce normal mammary gland development without the presence of GH. In addition to IGF-1, other paracrine growth factors such as epidermal growth factor, transforming growth factor beta, amphiregulin, fibroblast growth factor, and hepatocyte growth factor are involved in breast development as mediators downstream to sex hormones and GH/IGF-1.During embryonic development, IGF-1 levels are low, and gradually increase from birth to puberty. At puberty, the levels of GH and IGF-1 reach their highest levels in life and estrogen begins to be secreted in high amounts in females, which is when ductal development mostly takes place. Under the influence of estrogen, stromal and fat tissue surrounding the ductal system in the mammary glands also grows. After puberty, GH and IGF-1 levels progressively decrease, which limits further development until pregnancy, if it occurs. 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.
Androgens such as testosterone inhibit estrogen-mediated mammary gland development through activation of androgen receptors expressed in mammary gland tissue, and in conjunction with relatively low estrogen levels, are the cause of the lack of developed mammary glands in males.
Timeline
Before birth
Mammary gland development is characterized by the unique process by which the epithelium invades the stroma. The development of the mammary gland occurs mainly after birth. During puberty, tubule formation is coupled with branching morphogenesis which establishes the basic arboreal network of ducts emanating from the nipple.Developmentally, mammary gland epithelium is constantly produced and maintained by rare epithelial cells, dubbed as mammary progenitors which are ultimately thought to be derived from tissue-resident stem cells.
Embryonic mammary gland development can be divided into a series of specific stages. 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. The second stage occurs at E11.5 when placode formation begins along the mammary milk line. This will eventually give rise to the nipple. 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.
The primitive cells are detected in embryo and their numbers increase steadily during development
Growth
ly, the mammary ducts elongate into the mammary fat pad. 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. This developmental period is characterized by the emergence of the terminal end buds and lasts until an age of about 7–8 weeks.By the pubertal stage, the mammary ducts have invaded to the end of the mammary fat pad. At this point, the terminal end buds become less proliferative and decrease in size. Side branches form from the primary ducts and begin to fill the mammary fat pad. Ductal development decreases with the arrival of sexual maturity and undergoes estrous cycles. As a result of estrous cycling, the mammary gland undergoes dynamic changes where cells proliferate and then regress in an ordered fashion.