View source for Mammary gland

{{Short description|Exocrine gland in humans and other mammals}}
{{Redirect|Mammary|the mountain in Alaska|Mammary Peak}}
{{Use dmy dates|date=September 2020}}
{{Infobox anatomy
| Name        = Mammary gland      
| Greek       =
| Image       = Breast anatomy normal scheme.png
| Caption     = Cross-section of the human mammary gland: {{ordered list |style=text-align: left; |[[Chest wall]] |[[Pectoralis major muscle|Pectoralis muscles]] |[[Lobules]] |[[Nipple]] |[[Areola]] |[[Lactiferous duct|Milk duct]] |[[Adipose tissue|Fatty tissue]] |[[Human skin|Skin]]}}
| Width       =
| Precursor   = [[Mesoderm]]<br />&nbsp;<small>(blood vessels and connective tissue)</small><br />Ectoderm<ref>{{cite book|url=http://www.bartleby.com/107/271.html|last=Gray|first=Henry|title=Anatomy of the Human Body|year=1918}}</ref><br />&nbsp;<small>(cellular elements)</small>
| System      =
| Artery      = [[Internal thoracic artery]]<br />[[Lateral thoracic artery]]<ref name=macea06 />
| Vein        = [[Internal thoracic vein]]<br />[[Axillary vein]]<ref name=macea06 />
| Nerve       = [[Supraclavicular nerves]]<br />[[Intercostal nerves]]<ref>{{cite book|last1=Lawrence|first1=Ruth A.|last2= Lawrence|first2= Robert M.|title=Breastfeeding: A Guide for the Medical Profession|publisher=Mosby/Elsevier|location=Maryland Heights, Maryland|isbn=978-1-4377-3590-1|edition=7th|page=54|date=2010-09-30}}</ref><br />&nbsp;<small>(lateral and medial branches)</small>
| Lymph       = [[Pectoral axillary lymph nodes]]<ref name=macea06>{{cite journal|last1=Macéa|first1=José Rafael|last2=Fregnani|first2= José Humberto Tavares Guerreiro|title=Anatomy of the Thoracic Wall, Axilla and Breast|journal=International Journal of Morphology|date=1 December 2006|volume=24|issue=4|doi=10.4067/S0717-95022006000500030|url=https://scielo.conicyt.cl/pdf/ijmorphol/v24n4/art30.pdf|doi-access=free}}</ref>
}}

A '''mammary gland''' is an [[exocrine gland]] that produces [[milk]] in [[human]]s and other [[mammal]]s. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in [[organ (anatomy)|organs]] such as the [[breast]]s in primates (for example, humans and chimpanzees), the [[udder]] in [[ruminant]]s (for example, cows, goats, sheep, and deer), and the [[wikt:dug#Noun|dugs]] of other animals (for example, dogs and cats) to feed young [[offspring]]. [[Galactorrhea|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 [[wikt:suckle#Verb|nursing]], occurs only in [[phenotype|phenotypic]] [[female]]s who have [[gestation|gestated]] in recent months or years. It is directed by hormonal guidance from [[sex steroid]]s. 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: [[Monotreme|monotremes]], [[Metatheria|metatherians]], and [[Eutheria|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 [[udder]]s. In the case of breasts, each mammary gland has its own nipple (e.g., human mammary glands). In the case of udders, pairs of mammary glands comprise a single mass, with more than one nipple (or [[teat]]) 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==
{{See also|Breast}}

The basic components of a mature mammary gland are the ''[[Mammary alveolus|alveoli]]'' (hollow cavities, a few millimeters large), which are lined with milk-secreting [[cuboidal cells]] and surrounded by [[myoepithelial cell]]s. 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.<ref name="Newton, M. & Newton, N.R. 1948">{{cite journal
|last1=Newton
|first1=Michael
|last2=Newton
|first2=Niles Rumely
|title=The let-down reflex in human lactation
|journal=The Journal of Pediatrics
|date=December 1948
|volume=33
|issue=6
|pages=698–704
|doi=10.1016/S0022-3476(48)80075-2
|pmid=18101061
}}</ref>

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."<ref>{{Cite journal|last1=Zucca-Matthes|first1=Gustavo|last2=Urban|first2=Cícero|last3=Vallejo|first3=André|date=February 2016|title=Anatomy of the nipple and breast ducts|journal=Gland Surgery|volume=5|issue=1|pages=32–36|doi=10.3978/j.issn.2227-684X.2015.05.10|issn=2227-684X|pmc=4716863|pmid=26855906}}</ref> The presence of more than two nipples is known as [[polythelia]] and the presence of more than two complex mammary glands as [[Accessory breast|polymastia]].

Maintaining the correct polarized morphology of the lactiferous duct tree requires another essential component – mammary epithelial cells [[extracellular matrix]] (ECM) which, together with [[adipocyte]]s, [[fibroblast]], inflammatory cells, and others, constitute mammary stroma.<ref name="Watson, C.J. 2008">{{Cite journal
| last1 = Watson | first1 = C. J.
| last2 = Khaled | first2 = W. T.
| doi = 10.1242/dev.005439
| title = Mammary development in the embryo and adult: A journey of morphogenesis and commitment
| journal = Development
| volume = 135
| issue = 6
| pages = 995–1003
| year = 2008
| pmid = 18296651
| s2cid = 9089976
| doi-access = 
}}</ref> 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.<ref name="Wiseman, B.S. 2002">{{Cite journal
| last1 = Wiseman | first1 = B. S.
| last2 = Werb | first2 = Z.
| title = Stromal Effects on Mammary Gland Development and Breast Cancer
| doi = 10.1126/science.1067431
| journal = Science
| volume = 296
| issue = 5570
| pages = 1046–1049
| year = 2002
| pmid = 12004111
| pmc =2788989
| bibcode = 2002Sci...296.1046W
}}</ref><ref name="Pavlovich_2010">{{Cite journal
| last1 = Pavlovich | first1 = A. L.
| last2 = Manivannan | first2 = S.
| last3 = Nelson | first3 = C. M.
| doi = 10.1089/ten.TEA.2009.0836
| title = Adipose Stroma Induces Branching Morphogenesis of Engineered Epithelial Tubules
| journal = Tissue Engineering Part A
| volume = 16
| issue = 12
| pages = 3719–3726
| year = 2010
| pmid = 20649458
| pmc =2991209
}}</ref>

===Histology===
[[File:Normal breast histology.png|thumb|Normal histology of the breast]]
[[File:Glandula mammaria.jpg|thumb|upright|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).]]
A mammary gland is a specific type of [[apocrine]] gland specialized for manufacture of [[colostrum]] (first milk) 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 gland]]s.<ref name="Moore2018">{{cite book |last1=Moore |first1=Keith L. |last2=Dalley |first2=Arthur F. |last3=Agur |first3=Anne M. R. |title=Clinically oriented anatomy |date=2018 |publisher=Wolters Kluwer |location=Philadelphia Baltimore New York London Buenos Aires Hong Kong Sydney Tokyo |isbn=978-1-4963-4721-3 |page=318 |edition=Eighth}}</ref><ref name=Ackerman2005>Ackerman (2005) ch.1 [http://www.derm101.com/content/13501 ''Apocrine Units''] {{webarchive|url=https://web.archive.org/web/20110421033058/http://www.derm101.com/content/13501 |date=21 April 2011 }}</ref><ref name=krstic04>{{cite book| publisher = Springer| isbn = 978-3-540-53666-6| last = Krstic| first = Radivoj V.| title = Human Microscopic Anatomy: An Atlas for Students of Medicine and Biology| date = 18 March 2004|page=466}}</ref>

==Development==
{{further|Breast development|Parathyroid hormone-related protein}}
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 (and maternal) hormones,<ref name="Watson, C.J. 2008"/> but is also under the (local) regulation of [[paracrine signalling|paracrine communication]] between neighboring epithelial and mesenchymal cells by parathyroid hormone-related protein ([[PTHrP]]).<ref>{{Cite journal
| last1 = Wysolmerski | first1 = J. J.
| last2 = Philbrick | first2 = W. M.
| last3 = Dunbar | first3 = M. E.
| last4 = Lanske | first4 = B.
| last5 = Kronenberg | first5 = H.
| last6 = Broadus | first6 = A. E.
| title = Rescue of the parathyroid hormone-related protein knockout mouse demonstrates that parathyroid hormone-related protein is essential for mammary gland development
| journal = Development
| volume = 125
| issue = 7
| pages = 1285–1294
| year = 1998
| doi = 10.1242/dev.125.7.1285
| pmid = 9477327
}}</ref> 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.<ref name="Watson, C.J. 2008"/> 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.<ref>{{Cite journal
| last1 = Hens | first1 = J. R.
| last2 = Wysolmerski | first2 = J. J.
| title = Key stages of mammary gland development: Molecular mechanisms involved in the formation of the embryonic mammary gland
| journal = Breast Cancer Research
| volume = 7
| issue = 5
| pages = 220–224
| doi = 10.1186/bcr1306
| year = 2005
| pmid = 16168142
| pmc =1242158
| doi-access = free
}}</ref> 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.<ref>{{Cite journal|last1=Montévil|first1=Maël|last2=Speroni|first2=Lucia|last3=Sonnenschein|first3=Carlos|last4=Soto|first4=Ana M.|date=2016-10-01|title=Modeling mammary organogenesis from biological first principles: Cells and their physical constraints|journal=Progress in Biophysics and Molecular Biology|series=From the Century of the Genome to the Century of the Organism: New Theoretical Approaches|volume=122|issue=1|pages=58–69|doi=10.1016/j.pbiomolbio.2016.08.004|pmid=27544910|pmc=5563449}}</ref>

===Biochemistry===
[[Estrogen]] and [[growth hormone]] (GH) are essential for the [[lactiferous duct|ductal]] component of mammary gland development, and act synergistically to mediate it.<ref name="Malley2010">{{Cite journal|title=Hormone Action in the Mammary Gland|author1=Brisken |author2=Malley |doi=10.1101/cshperspect.a003178|date=2 December 2010|pmc=2982168|volume=2|issue=12|article-number=a003178|journal=Cold Spring Harbor Perspectives in Biology|pmid=20739412}}</ref><ref name="pmid9516076">{{cite journal | vauthors = Kleinberg DL | title = Role of IGF-I in normal mammary development | journal = Breast Cancer Res. Treat. | volume = 47 | issue = 3 | pages = 201–8 | year = 1998 | pmid = 9516076 | doi = 10.1023/a:1005998832636| s2cid = 30440069 }}</ref><ref name="pmid10887519">{{cite journal | vauthors = Kleinberg DL | title = Early mammary development: growth hormone and IGF-1 | journal = J Mammary Gland Biol Neoplasia | volume = 2 | issue = 1 | pages = 49–57 | year = 1997 | pmid = 10887519 | doi = 10.1023/A:1026373513521| s2cid = 41667675 }}</ref><ref name="pmid10537134">{{cite journal | vauthors = Ruan W, Kleinberg DL | title = Insulin-like growth factor I is essential for terminal end bud formation and ductal morphogenesis during mammary development | journal = Endocrinology | volume = 140 | issue = 11 | pages = 5075–81 | year = 1999 | pmid = 10537134 | doi = 10.1210/endo.140.11.7095 | doi-access = free }}</ref><ref name="pmid10791764">{{cite journal | vauthors = Kleinberg DL, Feldman M, Ruan W | title = IGF-I: an essential factor in terminal end bud formation and ductal morphogenesis | journal = J Mammary Gland Biol Neoplasia | volume = 5 | issue = 1 | pages = 7–17 | year = 2000 | pmid = 10791764 | doi = 10.1023/A:1009507030633| s2cid = 25656770 }}</ref> Neither estrogen nor GH are capable of inducing ductal development without the other.<ref name="pmid9516076" /><ref name="pmid10887519" /><ref name="pmid10537134" /><ref name="pmid10791764" /> 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]] (IGF-1), which occurs both systemically (mainly originating from the [[liver]]) and locally in the mammary fat pad through activation of the [[growth hormone receptor]] (GHR).<ref name="pmid9516076" /><ref name="pmid10887519" /><ref name="pmid10537134" /><ref name="pmid10791764" /><ref name="pmid19034633">{{cite journal | vauthors = Kleinberg DL, Ruan W | title = IGF-I, GH, and sex steroid effects in normal mammary gland development | journal = J Mammary Gland Biol Neoplasia | volume = 13 | issue = 4 | pages = 353–60 | year = 2008 | pmid = 19034633 | doi = 10.1007/s10911-008-9103-7 | s2cid = 24786346 }}</ref> However, GH itself also acts independently of IGF-1 to stimulate ductal development by upregulating [[estrogen receptor]] (ER) expression in mammary gland tissue, which is a downstream effect of mammary gland GHR activation.<ref name="pmid10791764" /> 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.<ref name="pmid10791764" /> In addition to IGF-1, other [[paracrine]] [[growth factor]]s such as [[epidermal growth factor]] (EGF), [[transforming growth factor beta]] (TGF-β),<ref name="pmid16322320">{{cite journal | vauthors = Serra R, Crowley MR | title = Mouse models of transforming growth factor beta impact in breast development and cancer | journal = Endocr. Relat. Cancer | volume = 12 | issue = 4 | pages = 749–60 | year = 2005 | pmid = 16322320 | doi = 10.1677/erc.1.00936 | doi-access = free }}</ref> [[amphiregulin]],<ref name="pmid17659070">{{cite journal |author2-link=Jeffrey M. Rosen| vauthors = LaMarca HL, Rosen JM | title = Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage | journal = Breast Cancer Res. | volume = 9 | issue = 4 | article-number = 304 | year = 2007 | pmid = 17659070 | pmc = 2206713 | doi = 10.1186/bcr1740 | doi-access = free }}</ref> [[fibroblast growth factor]] (FGF), and [[hepatocyte growth factor]] (HGF)<ref name="pmid21934211">{{cite journal | vauthors = El-Attar HA, Sheta MI | title = Hepatocyte growth factor profile with breast cancer | journal = Indian J Pathol Microbiol | volume = 54 | issue = 3 | pages = 509–13 | year = 2011 | pmid = 21934211 | doi = 10.4103/0377-4929.85083 | doi-access = free }}</ref> are involved in breast development as mediators downstream to sex hormones and GH/IGF-1.<ref name="CoadDunstall2011">{{cite book|last1=Coad|first1=Jane|url=https://books.google.com/books?id=OmSKoYD-iW0C&pg=PA413|title=Anatomy and Physiology for Midwives|last2=Dunstall|first2=Melvyn|publisher=Elsevier Health Sciences|year=2011|isbn=978-0-7020-3489-3|pages=413–|author-link=Jane Coad}}</ref><ref name="HynesWatson2010">{{cite journal|last1=Hynes|first1=N. E.|last2=Watson|first2=C. J.|title=Mammary Gland Growth Factors: Roles in Normal Development and in Cancer|journal=Cold Spring Harbor Perspectives in Biology|volume=2|issue=8|year=2010|article-number=a003186|issn=1943-0264|doi=10.1101/cshperspect.a003186|pmid=20554705|pmc=2908768}}</ref><ref name="HarrisLippman2012">{{cite book|author1=Jay R. Harris|author2=Marc E. Lippman|author3=C. Kent Osborne|author4=Monica Morrow|title=Diseases of the Breast|url=https://books.google.com/books?id=GLc8xYe239kC&pg=PT94|date=28 March 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-4870-1|pages=94–}}</ref>

During embryonic development, IGF-1 levels are low, and gradually increase from birth to puberty.<ref name="pmid17595785">{{cite journal | vauthors = Chong YM, Subramanian A, Sharma AK, Mokbel K | title = The potential clinical applications of insulin-like growth factor-1 ligand in human breast cancer | journal = Anticancer Res. | volume = 27 | issue = 3B | pages = 1617–24 | year = 2007 | pmid = 17595785 | url = http://ar.iiarjournals.org/cgi/pmidlookup?view=long&pmid=17595785}}</ref> 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.<ref name="pmid17595785" /> Under the influence of estrogen, [[stroma (animal tissue)|stroma]]l and [[fat tissue]] surrounding the ductal system in the mammary glands also grows.<ref name="Johnson2003">{{cite book|author=Leonard R. Johnson|title=Essential Medical Physiology|url=https://books.google.com/books?id=j9e-tkdHeUoC&pg=PA770|year=2003|publisher=Academic Press|isbn=978-0-12-387584-6|pages=770–}}</ref> After puberty, GH and IGF-1 levels progressively decrease, which limits further development until [[pregnancy]], if it occurs.<ref name="pmid17595785" /> During pregnancy, [[progesterone]] and [[prolactin]] are essential for mediating [[lobuloalveolar]] development in estrogen-primed mammary gland tissue, which occurs in preparation of [[lactation]] and [[breastfeeding|nursing]].<ref name="Malley2010" /><ref name="pmid9098173">{{cite journal | vauthors = Jernström H, Olsson H | title = Breast size in relation to endogenous hormone levels, body constitution, and oral contraceptive use in healthy nulligravid women aged 19–25 years | journal = Am. J. Epidemiol. | volume = 145 | issue = 7 | pages = 571–80 | year = 1997 | pmid = 9098173 | doi = 10.1093/oxfordjournals.aje.a009153| doi-access = free }}</ref>

[[Androgen]]s such as [[testosterone]] inhibit estrogen-mediated mammary gland development (e.g., by reducing local ER expression) through activation of [[androgen receptor]]s expressed in mammary gland tissue,<ref name="pmid9098173" /><ref name="pmid10973921">{{cite journal | vauthors = Zhou J, Ng S, Adesanya-Famuiya O, Anderson K, Bondy CA | title = Testosterone inhibits estrogen-induced mammary epithelial proliferation and suppresses estrogen receptor expression | journal = FASEB J. | volume = 14 | issue = 12 | pages = 1725–30 | year = 2000 | pmid = 10973921 | doi = 10.1096/fj.99-0863com| doi-access = free | s2cid = 17172449 | url = https://zenodo.org/record/1236080 }}</ref> and in conjunction with relatively low estrogen levels, are the cause of the lack of developed mammary glands in males.<ref name="pmid24872741">{{cite journal | vauthors = Lemaine V, Cayci C, Simmons PS, Petty P | title = Gynecomastia in adolescent males | journal = Semin Plast Surg | volume = 27 | issue = 1 | pages = 56–61 | year = 2013 | pmid = 24872741 | pmc = 3706045 | doi = 10.1055/s-0033-1347166 }}</ref>

===Timeline===

====Before birth====
Mammary gland development is characterized by the unique process by which the [[epithelium]] invades the [[stroma (animal tissue)|stroma]]. The development of the mammary gland occurs mainly after [[birth]]. During [[puberty]], tubule formation is coupled with [[Morphogenesis#Branching morphogenesis|branching morphogenesis]] which establishes the basic arboreal network of ducts emanating from the [[nipple]].<ref>{{cite journal|last1=Sekhri|first1=KK|title=Studies of mouse mammary glands. I. Cytomorphology of the normal mammary gland|journal=J Natl Cancer Inst|date=Sep 1967|volume=39|issue=3|pages=459–90|pmid=6053715|first2=DR|last3=Deome|first3=KB|last2=Pitelka}}</ref>

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.<ref>{{Cite journal|last1=Tharmapalan|first1=Pirashaanthy|last2=Mahendralingam|first2=Mathepan|last3=Berman|first3=Hal K|last4=Khokha|first4=Rama|author-link4=Rama Khokha|date=2019-07-15|title=Mammary stem cells and progenitors: targeting the roots of breast cancer for prevention|journal=The EMBO Journal|volume=38|issue=14|article-number=e100852|doi=10.15252/embj.2018100852|issn=0261-4189|pmc=6627238|pmid=31267556}}</ref>

[[Embryo]]nic 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 (E10.5). 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 (biology)]].<ref>{{cite journal|last=Hens|first=JR|author2=Wysolmerski JJ|title=Key stages of mammary gland development: molecular mechanisms involved in the formation of the embryonic mammary gland|journal=Breast Cancer Res.|date=10 August 2005|volume=7|issue=5|pages=220–4|pmid=16168142|doi=10.1186/bcr1306|pmc=1242158 |doi-access=free }}</ref>

The primitive (stem) cells are detected in embryo and their numbers increase steadily during development<ref>{{cite journal|last=Makarem|first=M|author2=Eaves C|title=Stem Cells and the Developing Mammary Gland|journal=J Mammary Gland Biol Neoplasia|date=Apr 2013|doi=10.1007/s10911-013-9284-6|volume=18|issue=2|pages=209–19|pmid=23624881|pmc=4161372}}</ref>

====Growth====
[[Postnatal]]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 cycle]]s (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.<ref>{{cite journal|last=Daniel|first=CW|author2=Smith, GH|title=The mammary gland: a model for development|journal=Journal of Mammary Gland Biology and Neoplasia|date=January 1999|volume=4|issue=1|pages=3–8|pmid=10219902|doi=10.1023/A:1018796301609|s2cid=36670489}}</ref>

====Pregnancy====
During [[pregnancy]], the ductal systems undergo rapid proliferation and form [[Mammary alveolus|alveolar]] structures within the branches to be used for milk production. After delivery, [[lactation]] occurs within the mammary gland; lactation involves the secretion of milk by the [[Lumen (anatomy)|luminal cells]] in the alveoli. Contraction of the [[myoepithelial cells]] surrounding the alveoli will cause the milk to be ejected through the ducts and into the nipple for the nursing infant. Upon [[weaning]] of the infant, lactation stops and the mammary gland turns in on itself, a process called ''involution''. This process involves the controlled collapse of mammary epithelial cells where cells begin [[apoptosis]] in a controlled manner, reverting the mammary gland back to a pubertal state.

====Postmenopausal====
During [[postmenopause]], due to much lower levels of estrogen, and due to lower levels of GH and IGF-1, which decrease with age, mammary gland tissue atrophies and the mammary glands become smaller.

==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,<ref>{{Cite journal
| last1 = Sternlicht | first1 = M. D.
| title = Key stages in mammary gland development: The cues that regulate ductal branching morphogenesis
| journal = Breast Cancer Research
| volume = 8
| issue = 1
| pages = 201–203
| doi = 10.1186/bcr1368
| year = 2006
| article-number = 201
| pmid = 16524451
| pmc =1413974
| doi-access = free
}}</ref> 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]] (TEB), secondary branches sprouting from primary ducts<ref name="Wiseman, B.S. 2002"/><ref>{{Cite journal
| last1 = Sternlicht | first1 = M. D.
| last2 = Kouros-Mehr | first2 = H.
| last3 = Lu | first3 = P.
| last4 = Werb | first4 = Z.
| title = Hormonal and local control of mammary branching morphogenesis
| doi = 10.1111/j.1432-0436.2006.00105.x
| journal = Differentiation
| volume = 74
| issue = 7
| pages = 365–381
| year = 2006
| pmid = 16916375
| pmc =2580831
}}</ref> 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 cell|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.<ref>{{Cite journal
| last1 = Fata | first1 = J. E.
| last2 = Werb | first2 = Z.
| last3 = Bissell | first3 = M. J.
| title = Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes
| journal = Breast Cancer Research
| volume = 6
| issue = 1
| pages = 1–11
| doi = 10.1186/bcr634
| year = 2003
| pmid = 14680479
| pmc =314442
| doi-access = free
}}</ref> Important players include [[integrin|beta-1 integrin]], [[epidermal growth factor receptor]] (EGFR), [[laminin|laminin-1/5]], [[collagen|collagen-IV]], [[matrix metalloproteinase]] (MMPs), [[Heparan sulfate#Proteoglycans|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 (duct) epithelial cells, and the increased amount of activated MMPs can degrade surrounding ECM helping duct buds to reach further in the fat pads.<ref>{{Cite journal
| last1 = Wiseman | first1 = B. S.
| last2 = Sternlicht | first2 = M. D.
| last3 = Lund | first3 = L. R.
| last4 = Alexander | first4 = C. M.
| last5 = Mott | first5 = J.
| last6 = Bissell | first6 = M. J.
| last7 = Soloway | first7 = P.
| last8 = Itohara | first8 = S.
| last9 = Werb | first9 = Z.
| title = Site-specific inductive and inhibitory activities of MMP-2 and MMP-3 orchestrate mammary gland branching morphogenesis
| doi = 10.1083/jcb.200302090
| journal = The Journal of Cell Biology
| volume = 162
| issue = 6
| pages = 1123–1133
| year = 2003
| pmid = 12975354
| pmc =2172848
}}</ref><ref>{{Cite journal
| doi = 10.1083/jcb.148.3.615
| last1 = Koshikawa | first1 = N.
| last2 = Giannelli | first2 = G.
| last3 = Cirulli | first3 = V.
| last4 = Miyazaki | first4 = K.
| last5 = Quaranta | first5 = V.
| title = Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin-5
| journal = The Journal of Cell Biology
| volume = 148
| issue = 3
| pages = 615–624
| year = 2000
| pmid = 10662785
| pmc = 2174802
}}</ref> 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.<ref name="Wiseman, B.S. 2002"/> Degraded basement membrane fragments (laminin-5) roles to lead the way of mammary epithelial cells migration.<ref>{{Cite journal
| last1 = Dogic | first1 = D.
| last2 = Rousselle | first2 = P.
| last3 = Aumailley | first3 = M.
| title = Cell adhesion to laminin 1 or 5 induces isoform-specific clustering of integrins and other focal adhesion components
| journal = Journal of Cell Science
| volume = 111
| pages = 793–802
| year = 1998 |url=http://jcs.biologists.org/content/111/6/793.full.pdf
| pmid = 9472007 | issue=6
| doi = 10.1242/jcs.111.6.793
}}</ref> Whereas, [[laminin]]-1 interacts with non-integrin receptor [[dystroglycan]] negatively regulates this side branching process in case of [[cancer]].<ref>{{Cite journal
| last1 = Muschler | first1 = J.
| last2 = Levy | first2 = D.
| last3 = Boudreau | first3 = R.
| last4 = Henry | first4 = M.
| last5 = Campbell | first5 = K.
| last6 = Bissell | first6 = M. J.
| title = A role for dystroglycan in epithelial polarization: Loss of function in breast tumor cells
| journal = Cancer Research
| volume = 62
| issue = 23
| pages = 7102–7109
| year = 2002
| pmid = 12460932
}}</ref> 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.<ref>{{cite journal |author=Kurzer MS |title=Hormonal effects of soy in premenopausal women and men |journal=The Journal of Nutrition |volume=132 |issue=3 |pages=570S–573S |date=March 2002  |pmid=11880595 |doi= 10.1093/jn/132.3.570S|doi-access=free }} Also cited by {{cite journal |vauthors=Petrakis NL, Barnes S, King EB, Lowenstein J, Wiencke J, Lee MM, Miike R, Kirk M, Coward L |title=Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal people AFAB |journal=Cancer Epidemiology, Biomarkers & Prevention |volume=5 |issue=10 |pages=785–94 |date=October 1996  |pmid=8896889 |type=review}}</ref>

===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, [[Wnt signaling pathway|Wnt]]s secreted from mammary epithelial cells act paracrinely to induce more neighboring cells' branching.<ref>{{Cite journal
| last1 = Robinson | first1 = G. W.
| last2 = Hennighausen | first2 = L.
| last3 = Johnson | first3 = P. F.
| title = Side-branching in the mammary gland: The progesterone-Wnt connection
| journal = Genes & Development
| volume = 14
| issue = 8
| pages = 889–894
| year = 2000
| doi = 10.1101/gad.14.8.889
| pmid = 10783160
| s2cid = 2319046
| doi-access = free
}}</ref><ref>{{Cite journal
| last1 = Brisken | first1 = C.
| last2 = Heineman | first2 = A.
| last3 = Chavarria | first3 = T.
| last4 = Elenbaas | first4 = B.
| last5 = Tan | first5 = J.
| last6 = Dey | first6 = S. K.
| last7 = McMahon | first7 = J. A.
| last8 = McMahon | first8 = A. P.
| last9 = Weinberg | first9 = R. A.
| title = Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling
| journal = Genes & Development
| volume = 14
| issue = 6
| pages = 650–654
| year = 2000
| doi = 10.1101/gad.14.6.650
| pmid = 10733525
| pmc = 316462
}}</ref> 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 ([[lactation]]) 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.<ref name="Streuli, C.H. 1991">{{Cite journal
| doi = 10.1083/jcb.115.5.1383
| last1 = Streuli | first1 = C. H.
| last2 = Bailey | first2 = N.
| last3 = Bissell | first3 = M. J.
| title = Control of mammary epithelial differentiation: Basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity
| journal = The Journal of Cell Biology
| volume = 115
| issue = 5
| pages = 1383–1395
| year = 1991
| pmid = 1955479
| pmc = 2289247
}}</ref><ref name="Streuli, C.H. 1995">{{Cite journal
| doi = 10.1083/jcb.129.3.591
| last1 = Streuli | first1 = C. H.
| last2 = Schmidhauser | first2 = C.
| last3 = Bailey | first3 = N.
| last4 = Yurchenco | first4 = P.
| last5 = Skubitz | first5 = A. P.
| last6 = Roskelley | first6 = C.
| last7 = Bissell | first7 = M. J.
| title = Laminin mediates tissue-specific gene expression in mammary epithelia
| journal = The Journal of Cell Biology
| volume = 129
| issue = 3
| pages = 591–603
| year = 1995
| pmid = 7730398
| pmc = 2120432
}}</ref> Their binding ensures correct placement of prolactin receptors on the basal lateral side of alveoli cells and directional secretion of milk into lactiferous ducts.<ref name="Streuli, C.H. 1991"/><ref name="Streuli, C.H. 1995"/> 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 (baby suckling), and changes in osmotic balance caused by milk stasis and leaking of tight junctions cause cessation of milk production. It is the (passive) process of a child or animal ceasing to be dependent on the mother for nourishment. In some species there is complete or partial [[involution (medicine)|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.<ref>{{cite journal|author1=Nicholas L. Petrakis|author2=Lynn Mason|author3=Rose Lee|author4=Barbara Sugimoto|author5=Stella Pawson|author6=Frank Catchpool|title=Association of Race, Age, Menopausal Status, and Cerumen Type With Breast Fluid Secretion in Nonlactating Women, as Determined by Nipple Aspiration|journal=Journal of the National Cancer Institute |date=1975|volume=54|number=4|pages=829–834|doi=10.1093/jnci/54.4.829|pmid=1168727}}</ref> 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.<ref>{{Cite journal
| last1 = Zarzynska | first1 = J.
| last2 = Motyl | first2 = T.
| title = Apoptosis and autophagy in involuting bovine mammary gland
| journal = Journal of Physiology and Pharmacology
| volume = 59
| pages = 275–288
| year = 2008
| issue = Suppl 9
| pmid = 19261986
}}</ref><ref>{{Cite journal
| doi = 10.1023/A:1011384009787
| last1 = Fadok | first1 = V. A.
| title = Clearance: The last and often forgotten stage of apoptosis
| journal = Journal of Mammary Gland Biology and Neoplasia
| volume = 4
| issue = 2
| pages = 203–211
| year = 1999
| pmid = 10426399
| s2cid = 5926448 }}</ref> 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.<ref>{{Cite journal
| pmid = 17228094
| year = 2006
| last1 = Motyl | first1 = T.
| last2 = Gajkowska | first2 = B.
| last3 = Zarzyńska | first3 = J.
| last4 = Gajewska | first4 = M.
| last5 = Lamparska-Przybysz | first5 = M.
| title = Apoptosis and autophagy in mammary gland remodeling and breast cancer chemotherapy
| volume = 57
| pages = 17–32
| journal = Journal of Physiology and Pharmacology
| issue = Suppl 7
}}</ref> 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,<ref>{{Cite journal
| last1 = Gudjonsson | first1 = T.
| last2 = Rønnov-Jessen | first2 = L.
| last3 = Villadsen | first3 = R.
| last4 = Rank | first4 = F.
| last5 = Bissell | first5 = M. J.
| last6 = Petersen | first6 = O. W.
| title = Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition
| journal = Journal of Cell Science
| volume = 115
| issue = Pt 1
| pages = 39–50
| year = 2002
| doi = 10.1242/jcs.115.1.39
| pmid = 11801722
| pmc = 2933194
}}</ref> or from a mechanical change in the tension of mammary stroma.<ref>{{Cite journal
| last1 = Provenzano | first1 = P. P.
| last2 = Inman | first2 = D. R.
| last3 = Eliceiri | first3 = K. W.
| last4 = Knittel | first4 = J. G.
| last5 = Yan | first5 = L.
| last6 = Rueden | first6 = C. T.
| last7 = White | first7 = J. G.
| last8 = Keely | first8 = P. J.
| doi = 10.1186/1741-7015-6-11
| title = Collagen density promotes mammary tumor initiation and progression
| journal = BMC Medicine
| volume = 6
| article-number = 11
| year = 2008
| pmid = 18442412
| pmc =2386807
| doi-access = free
}} {{open access}}</ref> 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 breasts of female humans vary from most other mammals that tend to have less conspicuous mammary glands. The number and positioning of mammary glands varies widely in different mammals. The protruding teats and accompanying glands can be located anywhere along the two [[milk line]]s. 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 teats varies from 2 (in most primates) to 18 (in pigs). The [[Virginia opossum]] has 13, one of the few mammals with an odd number.<ref name="With the Wild Things – Transcripts">{{cite web |url=http://digitalcollections.fiu.edu/wild/transcripts/possums1.htm |title=With the Wild Things – Transcripts |publisher=Digitalcollections.fiu.edu |access-date=2013-04-05 |archive-url=https://web.archive.org/web/20130323001102/http://digitalcollections.fiu.edu/wild/transcripts/possums1.htm |archive-date=23 March 2013}}</ref><ref name="Raising Orphaned Baby Opossums">Stockard, Mary (2005) [https://web.archive.org/web/20100701012225/http://www.awrc.org/Baby%20Opossums.htm Raising Orphaned Baby Opossums]. Alabama Wildlife Center.</ref> The following table lists the number and position of teats and glands found in a range of mammals:

{| class="wikitable" style="margin-left: auto; margin-right: auto;"
!Species<ref>{{cite book|author1=Cunningham, Merle |author2=LaTour, Mickey A. |author3=Acker, Duane  |name-list-style=amp |title=Animal Science and Industry|isbn= 978-0-13-046256-5|publisher=Pearson Prentice Hall|year=2005}}</ref>
!Anterior<br />([[thoracic]])
!Intermediate<br />([[abdominal]])
!Posterior<br />([[Groin|inguinal]])
!Total
|-
|[[Goat]], [[sheep]], [[horse]]<br /> [[guinea pig]]
|0
|0
|2
|2
|-
|[[Cattle]]
|0
|0
|4
|4
|-
|[[Cat]]
|2
|2
|4
|8
|-
|[[Dog]]<ref>Dog breeds vary in the number of mammary glands: larger breeds tend to have 5 pairs, smaller breeds have 4 pairs.{{citation needed|date=December 2017}}</ref>
|4
|2
|2 or 4
|8 or 10
|-
|[[Mouse]]
|6
|0
|4
|10
|-
|[[Rat]]
|6
|2
|4
|12
|-
|[[Pig]]
|6
|6
|6
|18
|-
|[[Proboscidean]]s, [[primates]]
|2
|0
|0
|2
|-
|[[Virginia opossum]]<ref name="With the Wild Things – Transcripts"/><ref name="Raising Orphaned Baby Opossums"/>
|0
|0
|13
|13
|-
|[[Southern red-sided opossum]]<ref>P Smith 2008 [http://www.faunaparaguay.com/mamm26Monodelphissorex.pdf Red-Sided Short-Tailed Opossum].  Fauna Paraguay</ref>
|0
|0
|25 to 27
|25 to 27
|}

Male mammals typically have rudimentary mammary glands and nipples, with a few exceptions: male mice do not have nipples,<ref name="Mayer et al">{{Cite journal|pmc=2570124|title=Conversion of the Nipple to Hair-Bearing Epithelia by Lowering Bone Morphogenetic Protein Pathway Activity at the Dermal-Epidermal Interface|author1=Julie Ann Mayer|author2=John Foley|author3=Damon De La Cruz|author-link4=Cheng-Ming Chuong|author4=Cheng-Ming Chuong|author5=Randall Widelitz|date=November 2008|pmid=18832580|doi=10.2353/ajpath.2008.070920|volume=173|issue=5|journal=Am J Pathol|pages=1339–48}}</ref> male [[marsupial]]s do not have mammary glands,<ref name="ArmatiDickman2006">{{cite book|author1=Patricia J. Armati|author2=Chris R. Dickman|author3=Ian D. Hume|title=Marsupials|url=https://books.google.com/books?id=x3S5v971Nk0C&q=mammary%20glands|date=17 August 2006|publisher=Cambridge University Press|isbn=978-1-139-45742-2}}</ref> and male horses lack nipples.<ref>{{cite journal |last1= Hughes |first1=Katherine |date=2021 |title=Development and Pathology of the Equine Mammary Gland |url= |journal=Journal of Mammary Gland Biology and Neoplasia |volume=26 |issue=2 |pages=121–134 |doi=10.1007/s10911-020-09471-2 |pmid=33280071 |pmc=8236023 |doi-access=free }}</ref> The male [[dayak fruit bat]] has lactating mammary glands.<ref>{{Cite journal | last1 = Francis | first1 = C. M. | last2 = Anthony | first2 = E. L. P. | last3 = Brunton | first3 = J. A. | last4 = Kunz | first4 = T. H. | title = Lactation in male fruit bats | doi = 10.1038/367691a0 | journal = Nature | volume = 367 | issue = 6465 | pages = 691–692 | year = 1994 | url = http://www.bu.edu/cecb/files/2009/08/lactationmale-fruit-bats.pdf| bibcode = 1994Natur.367..691F | s2cid = 4369716 }}</ref> [[Male lactation]] occurs infrequently in some species.<ref name=Kunz_2009>{{Cite journal | last1 = Kunz | first1 = T | last2 = Hosken | first2 = D | doi = 10.1016/j.tree.2008.09.009 | title = Male lactation: why, why not and is it care? | journal = Trends in Ecology & Evolution | volume = 24 | issue = 2 | pages = 80–85 | year = 2009 | pmid = 19100649 | bibcode = 2009TEcoE..24...80K }}</ref>

Mammary glands are true [[protein]] factories,<ref>{{Cite journal|last1=Li|first1=Peng|last2=Knabe|first2=Darrell A.|last3=Kim|first3=Sung Woo|last4=Lynch|first4=Christopher J.|last5=Hutson|first5=Susan M.|last6=Wu|first6=Guoyao|date=2009-08-01|title=Lactating Porcine Mammary Tissue Catabolizes Branched-Chain Amino Acids for Glutamine and Aspartate Synthesis|journal=The Journal of Nutrition|language=en|volume=139|issue=8|pages=1502–1509|doi=10.3945/jn.109.105957|pmid=19549750|pmc=3151199|issn=0022-3166|doi-access=free}}</ref> and several labs have constructed [[Genetically modified organism|transgenic animal]]s, mainly [[goat]]s and [[cow]]s, to produce proteins for pharmaceutical use.<ref>{{cite web |url= https://www.bbc.co.uk/news/av/science-environment-16554357 |title=BBC News – The goats with spider genes and silk in their milk |work=bbc.co.uk |date=17 January 2012 |access-date=26 April 2012}}</ref> Complex [[glycoprotein]]s such as [[monoclonal antibody|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 culture]]s.

===Evolution===

There are many theories on how mammary glands evolved. For example, it is thought that the mammary gland is a transformed sweat gland, more closely related to [[apocrine sweat glands]].<ref>{{Cite journal
| doi = 10.1023/A:1022848632125
| last1 = Oftedal | first1 = O. T.
| title = The origin of lactation as a water source for parchment-shelled eggs
| journal = Journal of Mammary Gland Biology and Neoplasia
| volume = 7
| issue = 3
| pages = 253–266
| year = 2002
| pmid = 12751890
| s2cid = 8319185 }}</ref> Because 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—[[monotreme]]s, [[marsupial]]s, and [[eutheria]]ns. One theory proposes that mammary glands evolved from glands that were used to keep the eggs of early mammals moist<ref>[https://web.archive.org/web/20090419024229/http://nationalzoo.si.edu/ConservationAndScience/SpotlightOnScience/oftedalolav20030714.cfm Lactating on Eggs]. Smithsonian National Zoo, 14 July 2003.</ref><ref>{{Cite journal
 | doi = 10.1023/A:1022896515287
 | last1 = Oftedal
 | first1 = OT
 | title = The mammary gland and its origin during synapsid evolution
 | journal = Journal of Mammary Gland Biology and Neoplasia
 | volume = 7
 | issue = 3
 | pages = 225–52
 | year = 2002
 | pmid = 12751889
| s2cid = 25806501
 }}</ref> and free from infection<ref>[https://web.archive.org/web/20070312005054/http://scienceblogs.com/pharyngula/2006/05/breast_beginnings.php Breast beginnings]. scienceblogs.com</ref><ref>{{Cite journal
| last1 = Vorbach | first1 = C.
| last2 = Capecchi | first2 = M. R.
| last3 = Penninger | first3 = J. M.
| doi = 10.1002/bies.20423
| title = Evolution of the mammary gland from the innate immune system?
| journal = BioEssays
| volume = 28
| issue = 6
| pages = 606–616
| year = 2006
| pmid = 16700061
}}</ref> (monotremes still lay eggs). Other theories suggest that early secretions were used directly by hatched young,<ref>{{Cite journal
| last1 = Lefèvre | first1 = C. M.
| last2 = Sharp | first2 = J. A.
| last3 = Nicholas | first3 = K. R.
| title = Evolution of Lactation: Ancient Origin and Extreme Adaptations of the Lactation System
| doi = 10.1146/annurev-genom-082509-141806
| journal = Annual Review of Genomics and Human Genetics
| volume = 11
| pages = 219–238
| year = 2010
| pmid = 20565255
}}</ref> or that the secretions were used by young to help them orient to their mothers.<ref>{{Cite journal | last1 = Graves | first1 = B. M. | last2 = Duvall | first2 = D. | doi = 10.1086/284177 | title = A Role for Aggregation Pheromones in the Evolution of Mammallike Reptile Lactation | journal = The American Naturalist | volume = 122 | issue = 6 | page = 835 | year = 1983 | bibcode = 1983ANat..122..835G | s2cid = 84089647 }}</ref>

Lactation is thought to have developed long before the evolution of the mammary gland and mammals; see [[Lactation#Evolution|evolution of lactation]].

==Additional images==
<!--- It would be nice to have other, unusual examples, such as whales, seals, etc.. -->
<gallery class="center" mode="packed" heights="160">
Image:illu_breast_anatomy.jpg|Cross section of the breast of a human female
Image:Säugende Hündin.JPG|[[Dog]]
Image:Bezerro mamando REFON.jpg|[[Cattle]]
Image:White Cat Nursing Four Kittens HQ.jpg|[[Cat]]
Image:Piglets1.jpg|[[Pig]]
<!--Image:Baby sheep feeding.JPG|[[Sheep]] - Does not show teats-->
Image:Goat kid feeding on mothers milk.jpg|[[Goat]]
Image:Elephant_breastfeading.jpg|[[Elephant]]
Camelus dromedarius Euter Zoo Landau Juni 2011.JPG|[[Dromedary camel]]
Netzgiraffe Euter.JPG|[[Giraffe]]
</gallery>

==See also==
{{Anatomy-terms}}
{{col div|colwidth=30em}}
* [[Breastfeeding]]
* [[Mammary tumor]]
* [[Mammaglobin]]
* [[Gynecomastia]]
* [[Hypothalamic–pituitary–prolactin axis]]
* [[Udder]]
* [[Witch's milk]]
* [[Milk line]]
* [[List of glands of the human body#Skin]]
{{colend}}[[List of distinct cell types in the adult human body]]

== References ==
{{Reflist|35em|refs=
}}

== Bibliography ==
* {{cite book|last=Ackerman|first=A. Bernard|title=Histologic Diagnosis of Inflammatory Skin Diseases An Algorithmic Method Based on Pattern Analysis|year=2005|isbn=978-1-893357-25-9|url=http://www.derm101.com/content/13501|author2=Almut Böer|author3=Bruce Bennin|author4=Geoffrey J. Gottlieb|publisher=Ardor Scribendi |archive-url=https://web.archive.org/web/20110421033058/http://www.derm101.com/content/13501|archive-date=21 April 2011}}
* [[Keith L. Moore|Moore, Keith L.]] et al. (2010) ''Clinically Oriented Anatomy'' 6th Ed

== External links ==
{{EB1911 Poster|Mammary Gland}}
* [https://web.archive.org/web/20051201011719/http://classes.aces.uiuc.edu/AnSci308/anatomycompar.html Comparative Mammary Gland Anatomy] by W. L. Hurley
* [http://jdc.jefferson.edu/cooper/61/ On the anatomy of the breast] by Sir Astley Paston Cooper (1840). Numerous drawings, in the public domain.

{{Breast anatomy}}

{{Authority control}}

{{DEFAULTSORT:Mammary Gland}}
[[Category:Breast anatomy]]
[[Category:Exocrine system]]
[[Category:Glands]]
[[Category:Mammal anatomy]]
[[Category:Female mammals|*]]
[[Category:Human female endocrine system]]